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Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma (COLUMBUS)

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ClinicalTrials.gov Identifier: NCT01909453
Recruitment Status : Active, not recruiting
First Posted : July 26, 2013
Results First Posted : July 12, 2021
Last Update Posted : April 26, 2024
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: LGX818
Drug: MEK162
Drug: vemurafenib
Enrollment 921
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg
Hide Arm/Group Description Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Period Title: Overall Study
Started 192 194 191 258 86
Completed 0 0 0 0 0
Not Completed 192 194 191 258 86
Reason Not Completed
Ongoing             118             103             83             164             50
Death             69             74             88             86             29
Lost to Follow-up             3             4             4             3             3
Withdrawal by Subject             2             13             16             5             4
Arm/Group Title Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Total
Hide Arm/Group Description Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Total of all reporting groups
Overall Number of Baseline Participants 192 194 191 258 86 921
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomized participants.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 194 participants 191 participants 258 participants 86 participants 921 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
132
  68.8%
154
  79.4%
140
  73.3%
175
  67.8%
60
  69.8%
661
  71.8%
>=65 years
60
  31.3%
40
  20.6%
51
  26.7%
83
  32.2%
26
  30.2%
260
  28.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 194 participants 191 participants 258 participants 86 participants 921 participants
Female
77
  40.1%
86
  44.3%
80
  41.9%
107
  41.5%
42
  48.8%
392
  42.6%
Male
115
  59.9%
108
  55.7%
111
  58.1%
151
  58.5%
44
  51.2%
529
  57.4%
1.Primary Outcome
Title Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group
Hide Description PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm^2).
Time Frame From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 191
Median (95% Confidence Interval)
Unit of Measure: months
14.9
(11.0 to 18.5)
7.3
(5.6 to 8.2)
2.Primary Outcome
Title Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group
Hide Description PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2.
Time Frame From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 194
Median (95% Confidence Interval)
Unit of Measure: months
14.9
(11.0 to 18.5)
9.6
(7.4 to 14.8)
3.Secondary Outcome
Title Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group
Hide Description PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2.
Time Frame From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 258 86 280
Median (95% Confidence Interval)
Unit of Measure: months
12.9
(10.1 to 14.0)
7.4
(5.6 to 9.2)
9.2
(7.4 to 11.0)
4.Secondary Outcome
Title Part 1: Overall Survival (OS)
Hide Description Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a death had not been observed by the date of analysis cutoff, OS was censored at the date of last contact.
Time Frame From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Hide Description AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 192 186
Measure Type: Number
Unit of Measure: percentage of participants
Participants with AEs 98.4 99.5 99.5
Participants with SAEs 34.4 34.9 37.1
6.Secondary Outcome
Title Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03
Hide Description Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, 'Number analyzed' signifies number of participants evaluable for specified rows.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 192 186
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin (hypo) Number Analyzed 192 participants 192 participants 186 participants
19
   9.9%
11
   5.7%
13
   7.0%
Prothrombin international normalized ratio increased Number Analyzed 192 participants 188 participants 181 participants
0
   0.0%
1
   0.5%
3
   1.7%
Lymphocytes (hypo) Number Analyzed 192 participants 191 participants 186 participants
20
  10.4%
15
   7.9%
41
  22.0%
Lymphocytes (hyper) Number Analyzed 192 participants 191 participants 186 participants
14
   7.3%
11
   5.8%
5
   2.7%
Neutrophils (hypo) Number Analyzed 192 participants 192 participants 186 participants
14
   7.3%
5
   2.6%
3
   1.6%
Platelets (hypo) Number Analyzed 192 participants 192 participants 186 participants
2
   1.0%
1
   0.5%
1
   0.5%
Leukocytes (hypo) Number Analyzed 192 participants 192 participants 186 participants
5
   2.6%
3
   1.6%
4
   2.2%
Albumin (hypo) Number Analyzed 192 participants 192 participants 186 participants
3
   1.6%
5
   2.6%
2
   1.1%
Alkaline phosphatase Number Analyzed 192 participants 192 participants 186 participants
6
   3.1%
3
   1.6%
4
   2.2%
Alanine aminotransferase Number Analyzed 192 participants 192 participants 186 participants
15
   7.8%
8
   4.2%
8
   4.3%
Aspartate aminotransferase Number Analyzed 192 participants 192 participants 186 participants
12
   6.3%
4
   2.1%
4
   2.2%
Bilirubin Number Analyzed 192 participants 192 participants 186 participants
1
   0.5%
0
   0.0%
13
   7.0%
Creatine (phospho)kinase Number Analyzed 186 participants 182 participants 180 participants
32
  17.2%
1
   0.5%
1
   0.6%
Corrected Calcium (hypo) Number Analyzed 192 participants 191 participants 186 participants
1
   0.5%
1
   0.5%
3
   1.6%
Corrected Calcium (hyper) Number Analyzed 192 participants 191 participants 186 participants
0
   0.0%
0
   0.0%
2
   1.1%
Creatinine Number Analyzed 192 participants 192 participants 186 participants
35
  18.2%
15
   7.8%
48
  25.8%
Gamma-glutamyl transferase Number Analyzed 192 participants 191 participants 186 participants
43
  22.4%
29
  15.2%
15
   8.1%
Glucose serum fasting (hypo) Number Analyzed 155 participants 149 participants 125 participants
2
   1.3%
4
   2.7%
3
   2.4%
Glucose serum fasting (hyper) Number Analyzed 155 participants 149 participants 125 participants
20
  12.9%
12
   8.1%
12
   9.6%
Magnesium (hypo) Number Analyzed 192 participants 190 participants 186 participants
0
   0.0%
1
   0.5%
0
   0.0%
Magnesium (hyper) Number Analyzed 192 participants 190 participants 186 participants
2
   1.0%
0
   0.0%
1
   0.5%
Phosphate (hypo) Number Analyzed 192 participants 190 participants 186 participants
18
   9.4%
25
  13.2%
35
  18.8%
Potassium (hypo) Number Analyzed 192 participants 192 participants 186 participants
1
   0.5%
1
   0.5%
3
   1.6%
Potassium (hyper) Number Analyzed 192 participants 192 participants 186 participants
6
   3.1%
4
   2.1%
6
   3.2%
Sodium (hypo) Number Analyzed 192 participants 192 participants 186 participants
7
   3.6%
1
   0.5%
1
   0.5%
7.Secondary Outcome
Title Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Hide Description Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg. Low/high diastolic blood pressure (DBP) [mmHg]: <= 50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg. Low/high Pulse rate: <=50 beats per minute (bpm) with decrease from baseline of >=15 bpm/>= 120 bpm with increase from baseline of >=15 bpm. Low/high Weight [kilogram]: >=20 percent (%) decrease from baseline/>= 10% increase from baseline. Low/high Body temperature degree Celsius (C): <= 36 degree C/>= 37.5 degree C.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable at specified rows.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 188 185 184
Measure Type: Count of Participants
Unit of Measure: Participants
Sitting Pulse Rate (bpm): High Number Analyzed 186 participants 184 participants 182 participants
1
   0.5%
7
   3.8%
8
   4.4%
Sitting Pulse Rate (bpm): Low Number Analyzed 185 participants 181 participants 182 participants
3
   1.6%
8
   4.4%
2
   1.1%
Sitting Systolic Blood Pressure (mmHg): High Number Analyzed 177 participants 177 participants 173 participants
27
  15.3%
14
   7.9%
31
  17.9%
Sitting Systolic Blood Pressure (mmHg): Low Number Analyzed 188 participants 184 participants 182 participants
7
   3.7%
4
   2.2%
1
   0.5%
Sitting Diastolic Blood Pressure (mmHg): High Number Analyzed 182 participants 183 participants 181 participants
23
  12.6%
5
   2.7%
13
   7.2%
Sitting Diastolic Blood Pressure (mmHg): Low Number Analyzed 188 participants 185 participants 184 participants
9
   4.8%
7
   3.8%
5
   2.7%
Weight (kg): High Number Analyzed 187 participants 184 participants 184 participants
44
  23.5%
10
   5.4%
8
   4.3%
Weight (kg): Low Number Analyzed 187 participants 184 participants 184 participants
2
   1.1%
8
   4.3%
13
   7.1%
Body temperature (degree C): High Number Analyzed 185 participants 176 participants 181 participants
19
  10.3%
11
   6.3%
17
   9.4%
Body temperature (degree C): Low Number Analyzed 132 participants 134 participants 141 participants
76
  57.6%
74
  55.2%
57
  40.4%
8.Secondary Outcome
Title Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values
Hide Description Newly occurring notable ECG values were reported for QT (millisecond [ms]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (>) 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60. Heart rate: New <60, New >100 was considered as newly occurring notable value.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here "Overall Number of Participants analyzed" signifies number of participants evaluable for this outcome measure and 'Number analyzed' signifies number of participants evaluable for specified rows.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 187 180 179
Measure Type: Count of Participants
Unit of Measure: Participants
QT: Increase >30 ms Number Analyzed 187 participants 180 participants 179 participants
105
  56.1%
68
  37.8%
81
  45.3%
QT: Increase >60 ms Number Analyzed 187 participants 180 participants 179 participants
27
  14.4%
19
  10.6%
24
  13.4%
QT: New >450 ms Number Analyzed 180 participants 169 participants 173 participants
23
  12.8%
15
   8.9%
17
   9.8%
QT: New >480 ms Number Analyzed 187 participants 176 participants 178 participants
5
   2.7%
4
   2.3%
3
   1.7%
QT: New >500 ms Number Analyzed 187 participants 178 participants 179 participants
2
   1.1%
2
   1.1%
2
   1.1%
QTcF: Increase >30 ms Number Analyzed 186 participants 179 participants 179 participants
50
  26.9%
56
  31.3%
76
  42.5%
QTcF: Increase >60 ms Number Analyzed 186 participants 179 participants 179 participants
10
   5.4%
7
   3.9%
10
   5.6%
QTcF: New >450 ms Number Analyzed 178 participants 171 participants 174 participants
25
  14.0%
39
  22.8%
42
  24.1%
QTcF: New >480 ms Number Analyzed 186 participants 177 participants 179 participants
7
   3.8%
7
   4.0%
5
   2.8%
QTcF: New >500 ms Number Analyzed 186 participants 178 participants 179 participants
1
   0.5%
5
   2.8%
3
   1.7%
QTcB: Increase >30 ms Number Analyzed 184 participants 179 participants 177 participants
47
  25.5%
74
  41.3%
78
  44.1%
QTcB: Increase >60 ms Number Analyzed 184 participants 179 participants 177 participants
11
   6.0%
15
   8.4%
14
   7.9%
QTcB: New >450 ms Number Analyzed 155 participants 158 participants 155 participants
47
  30.3%
76
  48.1%
65
  41.9%
QTcB: New >480 ms Number Analyzed 183 participants 174 participants 176 participants
12
   6.6%
23
  13.2%
20
  11.4%
QTcB: New >500 ms Number Analyzed 183 participants 179 participants 177 participants
3
   1.6%
10
   5.6%
8
   4.5%
Heart rate: New <60 bpm Number Analyzed 163 participants 159 participants 153 participants
58
  35.6%
37
  23.3%
16
  10.5%
Heart rate: New <100 bpm Number Analyzed 182 participants 175 participants 170 participants
14
   7.7%
23
  13.1%
18
  10.6%
9.Secondary Outcome
Title Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
Hide Description Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
Arm/Group Title Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 192 186
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 0
127
  66.1%
161
  83.9%
161
  86.6%
Grade 2
56
  29.2%
17
   8.9%
16
   8.6%
Grade 3
3
   1.6%
4
   2.1%
2
   1.1%
Grade 4
0
   0.0%
0
   0.0%
0
   0.0%
Missing
6
   3.1%
10
   5.2%
7
   3.8%
10.Secondary Outcome
Title Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
Hide Description AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 192 186
Measure Type: Count of Participants
Unit of Measure: Participants
Rash
2
   1.0%
10
   5.2%
25
  13.4%
Skin infections
4
   2.1%
1
   0.5%
0
   0.0%
PPE syndrome
0
   0.0%
26
  13.5%
2
   1.1%
Photosensitivity
1
   0.5%
0
   0.0%
3
   1.6%
Nail disorders
0
   0.0%
0
   0.0%
0
   0.0%
Severe cutaneous adverse reactions
0
   0.0%
1
   0.5%
5
   2.7%
11.Secondary Outcome
Title Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
Hide Description AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 192 186
Measure Type: Count of Participants
Unit of Measure: Participants
Retinopathy excluding RVO
5
   2.6%
0
   0.0%
0
   0.0%
RVO
0
   0.0%
1
   0.5%
0
   0.0%
Uveitis-type events
1
   0.5%
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Hide Description AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 257 84 276
Measure Type: Number
Unit of Measure: percentage of Participants
AEs 98.1 96.4 98.6
SAEs 29.2 29.8 33.3
13.Secondary Outcome
Title Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0
Hide Description Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.0 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, 'Number analyzed' signifies number of participants evaluable for specified rows. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 257 84 276
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin (hypo) Number Analyzed 257 participants 84 participants 276 participants
16
   6.2%
5
   6.0%
16
   5.8%
Prothrombin international normalized ratio increased Number Analyzed 246 participants 80 participants 268 participants
4
   1.6%
0
   0.0%
1
   0.4%
Lymphocytes (hypo) Number Analyzed 257 participants 84 participants 275 participants
28
  10.9%
10
  11.9%
25
   9.1%
Lymphocytes (hyper) Number Analyzed 257 participants 84 participants 275 participants
11
   4.3%
2
   2.4%
13
   4.7%
Neutrophils (hypo) Number Analyzed 257 participants 84 participants 276 participants
19
   7.4%
4
   4.8%
9
   3.3%
Platelets (hypo) Number Analyzed 256 participants 84 participants 276 participants
1
   0.4%
1
   1.2%
2
   0.7%
Leukocytes (hypo) Number Analyzed 257 participants 84 participants 276 participants
3
   1.2%
2
   2.4%
5
   1.8%
Albumin (hypo) Number Analyzed 257 participants 84 participants 276 participants
7
   2.7%
4
   4.8%
9
   3.3%
Alkaline phosphatase (hyper) Number Analyzed 257 participants 84 participants 276 participants
11
   4.3%
1
   1.2%
4
   1.4%
Alanine aminotransferase Number Analyzed 257 participants 84 participants 276 participants
18
   7.0%
1
   1.2%
9
   3.3%
Aspartate aminotransferase Number Analyzed 257 participants 84 participants 276 participants
15
   5.8%
1
   1.2%
5
   1.8%
Bilirubin Number Analyzed 257 participants 84 participants 276 participants
2
   0.8%
0
   0.0%
0
   0.0%
Creatine kinase Number Analyzed 257 participants 76 participants 258 participants
40
  15.6%
0
   0.0%
1
   0.4%
Corrected Calcium (hypo) Number Analyzed 257 participants 84 participants 275 participants
4
   1.6%
1
   1.2%
2
   0.7%
Creatinine Number Analyzed 257 participants 84 participants 276 participants
44
  17.1%
11
  13.1%
26
   9.4%
Gamma-glutamyl transferase Number Analyzed 257 participants 84 participants 275 participants
38
  14.8%
9
  10.7%
38
  13.8%
Glucose serum fasting (hypo) Number Analyzed 257 participants 67 participants 216 participants
3
   1.2%
0
   0.0%
4
   1.9%
Glucose serum fasting (hyper) Number Analyzed 257 participants 67 participants 216 participants
27
  10.5%
5
   7.5%
17
   7.9%
Magnesium (hypo) Number Analyzed 257 participants 84 participants 274 participants
0
   0.0%
0
   0.0%
1
   0.4%
Magnesium (hyper) Number Analyzed 257 participants 84 participants 274 participants
3
   1.2%
0
   0.0%
0
   0.0%
Phosphate (hypo) Number Analyzed 257 participants 84 participants 274 participants
26
  10.1%
8
   9.5%
33
  12.0%
Potassium (hypo) Number Analyzed 257 participants 84 participants 276 participants
2
   0.8%
0
   0.0%
1
   0.4%
Potassium (hyper) Number Analyzed 257 participants 84 participants 276 participants
8
   3.1%
3
   3.6%
7
   2.5%
Sodium (hypo) Number Analyzed 257 participants 84 participants 276 participants
4
   1.6%
2
   2.4%
3
   1.1%
Sodium (hyper) Number Analyzed 257 participants 84 participants 276 participants
2
   0.8%
0
   0.0%
0
   0.0%
14.Secondary Outcome
Title Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Hide Description Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg, Low/high diastolic blood pressure (DBP) [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg, Low/high pulse rate [bpm]: <=50 bpm with decrease from baseline of >=15 bpm/>=120 bpm with increase from baseline of >=15 bpm, Low/high weight (kg): >=20 % decrease from baseline/>= 10% increase from baseline Low/high Body temperature degree C): <= 36°C/>= 37.5 degree C.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable at specified rows. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 256 80 265
Measure Type: Count of Participants
Unit of Measure: Participants
Sitting Pulse Rate (bpm): High Number Analyzed 252 participants 78 participants 262 participants
7
   2.8%
3
   3.8%
10
   3.8%
Sitting Pulse Rate (bpm): Low Number Analyzed 254 participants 77 participants 258 participants
11
   4.3%
1
   1.3%
9
   3.5%
Sitting Systolic Blood Pressure (mmHg): High Number Analyzed 243 participants 76 participants 253 participants
40
  16.5%
3
   3.9%
17
   6.7%
Sitting Systolic Blood Pressure (mmHg): Low Number Analyzed 255 participants 78 participants 262 participants
10
   3.9%
4
   5.1%
8
   3.1%
Sitting Diastolic Blood Pressure (mmHg): High Number Analyzed 253 participants 78 participants 261 participants
41
  16.2%
2
   2.6%
7
   2.7%
Sitting Diastolic Blood Pressure (mmHg): Low Number Analyzed 255 participants 77 participants 262 participants
7
   2.7%
2
   2.6%
9
   3.4%
Weight (kg): High Number Analyzed 256 participants 80 participants 264 participants
46
  18.0%
1
   1.3%
11
   4.2%
Weight (kg): Low Number Analyzed 256 participants 80 participants 264 participants
0
   0.0%
1
   1.3%
9
   3.4%
Body temperature (°C): High Number Analyzed 252 participants 77 participants 253 participants
14
   5.6%
5
   6.5%
16
   6.3%
Body temperature (°C): Low Number Analyzed 201 participants 55 participants 189 participants
120
  59.7%
22
  40.0%
96
  50.8%
15.Secondary Outcome
Title Part 2: Number of Participants With Newly Occurring Notable ECG Values
Hide Description Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New >450, New >480, New >500, increase from baseline >30, Increase from baseline >60. Heart rate: New < 60, New >100 was considered as newly occurring notable value.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable at specified rows. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 251 79 259
Measure Type: Count of Participants
Unit of Measure: Participants
QT (ms): Increase from baseline > 30 Number Analyzed 251 participants 79 participants 259 participants
132
  52.6%
27
  34.2%
95
  36.7%
QT (ms): Increase from baseline > 60 Number Analyzed 251 participants 79 participants 259 participants
34
  13.5%
6
   7.6%
25
   9.7%
QT (ms): New > 450 Number Analyzed 239 participants 76 participants 245 participants
34
  14.2%
5
   6.6%
20
   8.2%
QT (ms): New > 480 Number Analyzed 249 participants 79 participants 255 participants
9
   3.6%
2
   2.5%
6
   2.4%
QT (ms): New > 500 Number Analyzed 251 participants 79 participants 257 participants
4
   1.6%
0
   0.0%
2
   0.8%
QTcF (ms): Increase from baseline > 30 Number Analyzed 250 participants 78 participants 257 participants
59
  23.6%
20
  25.6%
76
  29.6%
QTcF (ms): Increase from baseline > 60 Number Analyzed 250 participants 78 participants 257 participants
13
   5.2%
7
   9.0%
14
   5.4%
QTcF (ms): New > 450 Number Analyzed 240 participants 70 participants 241 participants
36
  15.0%
11
  15.7%
50
  20.7%
QTcF (ms): New > 480 Number Analyzed 249 participants 78 participants 255 participants
11
   4.4%
5
   6.4%
12
   4.7%
QTcF (ms): New > 500 Number Analyzed 250 participants 78 participants 256 participants
2
   0.8%
1
   1.3%
6
   2.3%
QTcB (ms): New > 450 Number Analyzed 216 participants 67 participants 225 participants
70
  32.4%
28
  41.8%
104
  46.2%
QTcB (ms): New > 480 Number Analyzed 247 participants 77 participants 251 participants
23
   9.3%
6
   7.8%
29
  11.6%
QTcB (ms): New > 500 Number Analyzed 250 participants 79 participants 258 participants
10
   4.0%
1
   1.3%
11
   4.3%
QTcB (ms): Increase from baseline > 30 Number Analyzed 250 participants 79 participants 258 participants
69
  27.6%
24
  30.4%
98
  38.0%
QTcB (ms): Increase from baseline > 60 Number Analyzed 250 participants 79 participants 258 participants
22
   8.8%
8
  10.1%
23
   8.9%
Heart rate (bpm): New < 60 Number Analyzed 213 participants 67 participants 226 participants
82
  38.5%
5
   7.5%
42
  18.6%
Heart rate (bpm): New > 100 Number Analyzed 241 participants 74 participants 249 participants
8
   3.3%
10
  13.5%
33
  13.3%
16.Secondary Outcome
Title Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
Hide Description Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%;Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 257 84 276
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 0
181
  70.4%
74
  88.1%
235
  85.1%
Grade 2
71
  27.6%
5
   6.0%
22
   8.0%
Grade 3
3
   1.2%
0
   0.0%
4
   1.4%
Grade 4
0
   0.0%
0
   0.0%
0
   0.0%
Missing
2
   0.8%
5
   6.0%
15
   5.4%
17.Secondary Outcome
Title Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
Hide Description AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported are reported in this outcome measure.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set includes all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 257 84 276
Measure Type: Count of Participants
Unit of Measure: Participants
Rash
2
   0.8%
3
   3.6%
13
   4.7%
Skin infection
7
   2.7%
0
   0.0%
1
   0.4%
PPE syndrome
1
   0.4%
4
   4.8%
30
  10.9%
Photosensitivity
0
   0.0%
0
   0.0%
0
   0.0%
Nail disorders
0
   0.0%
0
   0.0%
0
   0.0%
Severe cutaneous adverse reactions
0
   0.0%
0
   0.0%
1
   0.4%
18.Secondary Outcome
Title Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
Hide Description AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
Time Frame Baseline up to 30 days after last dose of study drug (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set includes all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 257 84 276
Measure Type: Count of Participants
Unit of Measure: Participants
Retinopathy excluding RVO
4
   1.6%
0
   0.0%
0
   0.0%
RVO
0
   0.0%
0
   0.0%
1
   0.4%
Uveitis-type events
4
   1.6%
0
   0.0%
0
   0.0%
19.Secondary Outcome
Title Part 2: Overall Survival (OS)
Hide Description [Not Specified]
Time Frame From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Part 1 and Part 2: Objective Response Rate (ORR)
Hide Description ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response.
Time Frame From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 194 191 258 86 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.0
(55.8 to 69.9)
50.5
(43.3 to 57.8)
40.3
(33.3 to 47.6)
65.9
(59.8 to 71.7)
50.0
(39.0 to 61.0)
50.4
(44.3 to 56.4)
21.Secondary Outcome
Title Part 1 and Part 2: Time to Objective Response (TTR)
Hide Description TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit [FPFV] to last patient last visit [LPLV] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review.
Time Frame From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 194 191 258 86 280
Median (95% Confidence Interval)
Unit of Measure: months
1.9
(1.9 to 1.9)
2.0
(1.9 to 3.6)
2.1
(1.9 to 3.7)
1.9
(1.9 to 2.0)
1.9
(1.9 to 2.3)
1.9
(1.9 to 3.2)
22.Secondary Outcome
Title Part 1 and Part 2: Disease Control Rate (DCR)
Hide Description DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review.
Time Frame From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 194 191 258 86 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92.2
(87.4 to 95.6)
84.0
(78.1 to 88.9)
81.7
(75.4 to 86.9)
90.7
(86.5 to 93.9)
79.1
(69.0 to 87.1)
82.5
(77.5 to 86.8)
23.Secondary Outcome
Title Part 1 and Part 2: Duration of Response (DOR)
Hide Description DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response.
Time Frame From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all the participants who achieved at least once confirmed CR or PR. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 121 98 77 170 43 141
Median (95% Confidence Interval)
Unit of Measure: months
16.6
(12.2 to 20.4)
15.2 [1] 
(11.1 to NA)
12.3
(6.9 to 16.9)
12.7
(9.3 to 15.1)
7.5
(5.6 to 14.0)
12.9
(8.9 to 15.5)
[1]
Upper limit of 95% CI was not estimable due to low number of participants with events.
24.Secondary Outcome
Title Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
Hide Description FACT-M:melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items,not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.
Time Frame Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 194 191 258 86 280
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(22.1 to NA)
30.5
(18.4 to 30.5)
22.1 [2] 
(15.2 to NA)
NA [3] 
(NA to NA)
NA [1] 
(9.4 to NA)
20.5
(16.6 to 30.5)
[1]
Median and upper limit of 95% CI were not estimable due to low number of participants with events.
[2]
Upper limit of 95% CI was not estimable due to low number of participants with events.
[3]
Median and 95% CI were not estimable due to low number of participants with events.
25.Secondary Outcome
Title Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Hide Description EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score represented better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.
Time Frame Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 194 191 258 86 280
Median (95% Confidence Interval)
Unit of Measure: months
23.9 [1] 
(20.4 to NA)
14.7
(8.1 to 24.0)
16.6 [1] 
(11.9 to NA)
18.4
(16.8 to 19.1)
9.5 [1] 
(5.6 to NA)
11.1
(7.7 to 20.2)
[1]
Upper limit of 95% CI was not estimable due to low number of participants with events.
26.Secondary Outcome
Title Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Hide Description FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life.
Time Frame Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 165 177 159 234 83 260
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 165 participants 177 participants 159 participants 234 participants 83 participants 260 participants
52.39  (9.053) 52.76  (8.206) 52.01  (8.650) 52.08  (8.493) 51.13  (9.567) 52.24  (8.679)
Change at Cycle 3 Day 1 Number Analyzed 141 participants 148 participants 128 participants 212 participants 67 participants 215 participants
0.92  (9.539) -3.58  (8.133) -1.55  (9.023) 2.79  (7.296) -2.16  (9.700) -3.14  (8.654)
Change at Cycle 5 Day 1 Number Analyzed 128 participants 132 participants 106 participants 200 participants 60 participants 192 participants
-0.01  (9.157) -3.77  (7.576) -1.90  (7.572) 2.58  (7.244) -0.60  (7.948) -2.78  (7.814)
Change at Cycle 7 Day 1 Number Analyzed 120 participants 109 participants 84 participants 177 participants 52 participants 161 participants
1.35  (9.595) -3.05  (6.633) -2.19  (8.651) 2.64  (7.766) -3.14  (9.559) -3.08  (7.670)
Change at Cycle 9 Day 1 Number Analyzed 103 participants 79 participants 63 participants 161 participants 41 participants 120 participants
0.52  (9.096) -2.69  (6.513) -1.90  (7.491) 3.23  (7.720) -1.83  (7.323) -2.39  (6.782)
Change at Cycle 11 Day 1 Number Analyzed 87 participants 72 participants 46 participants 143 participants 31 participants 103 participants
0.18  (7.768) -3.67  (6.418) -0.51  (7.436) 2.54  (7.796) -2.41  (7.653) -3.29  (6.800)
Change at Cycle 13 Day 1 Number Analyzed 77 participants 65 participants 39 participants 126 participants 26 participants 91 participants
-0.33  (8.855) -2.71  (7.187) -0.97  (8.818) 1.97  (8.127) -3.31  (7.902) -2.88  (7.359)
Change at Cycle 15 Day 1 Number Analyzed 68 participants 56 participants 29 participants 95 participants 18 participants 74 participants
0.40  (7.943) -2.48  (6.829) -1.72  (9.906) 2.08  (9.196) -4.14  (5.662) -2.88  (6.566)
Change at Cycle 17 Day 1 Number Analyzed 58 participants 50 participants 23 participants 64 participants 14 participants 64 participants
0.27  (7.775) -1.66  (6.681) 0.70  (6.071) 2.45  (9.012) -2.64  (9.724) -1.88  (7.375)
Change at Cycle 19 Day 1 Number Analyzed 47 participants 51 participants 20 participants 26 participants 9 participants 60 participants
-0.59  (7.257) -2.80  (6.172) 0.23  (9.094) 1.23  (10.618) 0.00  (11.467) -2.38  (7.150)
Change at Cycle 21 Day 1 Number Analyzed 33 participants 39 participants 15 participants 12 participants 1 participants 40 participants
-0.69  (6.947) -2.59  (6.528) -3.33  (6.399) 2.58  (8.218) -2.00 -2.58  (6.445)
Change at Cycle 23 Day 1 Number Analyzed 22 participants 34 participants 12 participants 0 participants 0 participants 34 participants
-1.67  (7.003) -1.38  (6.818) -0.17  (4.687) -1.38  (6.818)
Change at Cycle 25 Day 1 Number Analyzed 18 participants 25 participants 7 participants 0 participants 0 participants 25 participants
-1.83  (6.205) -1.00  (6.880) -0.14  (5.305) -1.00  (6.880)
Change at End of treatment visit Number Analyzed 2 participants 8 participants 7 participants 6 participants 5 participants 13 participants
18.50  (23.335) -5.18  (11.458) -2.31  (4.715) 6.58  (7.197) -1.61  (9.115) -3.81  (10.370)
27.Secondary Outcome
Title Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Hide Description EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Time Frame Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 167 181 161 235 83 264
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 167 participants 181 participants 161 participants 235 participants 83 participants 264 participants
0.74  (0.210) 0.76  (0.181) 0.73  (0.222) 0.75  (0.219) 0.73  (0.244) 0.75  (0.203)
Change at Cycle 3 Day 1 Number Analyzed 153 participants 157 participants 143 participants 224 participants 67 participants 224 participants
0.05  (0.194) -0.10  (0.199) 0.00  (0.196) 0.06  (0.204) -0.06  (0.246) -0.09  (0.214)
Change at Cycle 5 Day 1 Number Analyzed 136 participants 139 participants 116 participants 206 participants 59 participants 198 participants
0.04  (0.196) -0.15  (0.220) -0.04  (0.196) 0.07  (0.218) -0.06  (0.231) -0.13  (0.227)
Change at Cycle 7 Day 1 Number Analyzed 125 participants 116 participants 88 participants 187 participants 53 participants 169 participants
0.05  (0.201) -0.13  (0.189) -0.03  (0.215) 0.06  (0.237) -0.16  (0.220) -0.14  (0.199)
Change at Cycle 9 Day 1 Number Analyzed 114 participants 87 participants 68 participants 163 participants 43 participants 130 participants
0.03  (0.237) -0.15  (0.197) -0.04  (0.237) 0.07  (0.192) -0.11  (0.202) -0.14  (0.199)
Change at Cycle 11 Day 1 Number Analyzed 95 participants 72 participants 50 participants 144 participants 33 participants 105 participants
0.04  (0.197) -0.18  (0.206) -0.01  (0.238) 0.06  (0.195) -0.16  (0.230) -0.17  (0.213)
Change at Cycle 13 Day 1 Number Analyzed 79 participants 63 participants 40 participants 130 participants 27 participants 90 participants
0.05  (0.225) -0.17  (0.206) -0.02  (0.263) 0.05  (0.254) -0.20  (0.216) -0.18  (0.208)
Change at Cycle 15 Day 1 Number Analyzed 69 participants 61 participants 29 participants 101 participants 17 participants 78 participants
0.05  (0.208) -0.18  (0.203) -0.07  (0.280) 0.05  (0.259) -0.26  (0.262) -0.20  (0.218)
Change at Cycle 17 Day 1 Number Analyzed 60 participants 56 participants 25 participants 66 participants 12 participants 68 participants
0.07  (0.193) -0.14  (0.165) -0.02  (0.173) 0.06  (0.188) -0.20  (0.332) -0.15  (0.203)
Change at Cycle 19 Day 1 Number Analyzed 49 participants 51 participants 22 participants 28 participants 9 participants 60 participants
0.03  (0.239) -0.18  (0.235) -0.02  (0.214) 0.05  (0.231) -0.11  (0.328) -0.17  (0.249)
Change at Cycle 21 Day 1 Number Analyzed 35 participants 42 participants 16 participants 12 participants 1 participants 43 participants
0.07  (0.132) -0.14  (0.198) -0.04  (0.159) 0.12  (0.174) -0.11 -0.14  (0.196)
Change at Cycle 23 Day 1 Number Analyzed 24 participants 33 participants 11 participants 0 participants 0 participants 33 participants
0.04  (0.139) -0.11  (0.147) -0.05  (0.171) -0.11  (0.147)
Change at Cycle 25 Day 1 Number Analyzed 16 participants 26 participants 5 participants 0 participants 0 participants 26 participants
0.07  (0.135) -0.11  (0.207) -0.17  (0.221) -0.11  (0.207)
Change at End of treatment visit Number Analyzed 3 participants 5 participants 3 participants 5 participants 4 participants 9 participants
0.03  (0.081) -0.09  (0.347) -0.14  (0.103) -0.27  (0.481) -0.06  (0.061) -0.08  (0.249)
28.Secondary Outcome
Title Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Hide Description EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms.
Time Frame Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 166 181 160 231 81 262
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 166 participants 181 participants 160 participants 231 participants 81 participants 262 participants
66.72  (21.585) 66.07  (21.890) 64.74  (23.611) 65.95  (23.028) 67.39  (22.095) 66.48  (21.920)
Change at Cycle 3 Day 1 Number Analyzed 152 participants 156 participants 135 participants 220 participants 69 participants 225 participants
3.56  (22.463) -7.64  (21.564) -3.46  (25.235) 4.47  (23.031) -4.95  (20.378) -6.81  (21.199)
Change at Cycle 5 Day 1 Number Analyzed 134 participants 138 participants 111 participants 205 participants 60 participants 198 participants
1.55  (23.441) -9.24  (21.611) -4.05  (23.700) 5.61  (19.396) -4.72  (22.776) -7.87  (22.011)
Change at Cycle 7 Day 1 Number Analyzed 125 participants 114 participants 85 participants 188 participants 53 participants 167 participants
1.53  (23.220) -9.21  (23.528) -3.04  (28.197) 5.01  (24.000) -7.08  (20.955) -8.53  (22.701)
Change at Cycle 9 Day 1 Number Analyzed 107 participants 88 participants 66 participants 157 participants 42 participants 130 participants
-0.55  (25.500) -12.03  (19.771) -6.94  (21.512) 4.94  (20.258) -8.73  (18.945) -10.96  (19.496)
Change at Cycle 11 Day 1 Number Analyzed 93 participants 71 participants 46 participants 147 participants 31 participants 102 participants
0.81  (21.670) -11.27  (20.611) -3.80  (22.202) 4.76  (21.212) -7.53  (19.288) -10.13  (20.197)
Change at Cycle 13 Day 1 Number Analyzed 79 participants 64 participants 37 participants 126 participants 26 participants 90 participants
0.42  (22.642) -8.59  (22.516) -2.93  (20.621) 5.89  (23.642) -9.29  (24.645) -8.80  (23.013)
Change at Cycle 15 Day 1 Number Analyzed 68 participants 58 participants 29 participants 101 participants 17 participants 75 participants
5.02  (19.108) -9.91  (23.490) -10.34  (29.852) 6.11  (21.695) -12.75  (21.270) -10.56  (22.897)
Change at Cycle 17 Day 1 Number Analyzed 61 participants 55 participants 24 participants 64 participants 14 participants 69 participants
0.41  (21.807) -8.03  (17.784) -6.94  (20.214) 5.86  (21.806) -7.14  (20.111) -7.85  (18.127)
Change at Cycle 19 Day 1 Number Analyzed 49 participants 50 participants 22 participants 27 participants 9 participants 59 participants
-0.51  (17.547) -9.33  (19.169) -1.89  (20.401) 1.23  (18.155) -0.93  (12.805) -8.05  (18.503)
Change at Cycle 21 Day 1 Number Analyzed 34 participants 43 participants 16 participants 11 participants 1 participants 44 participants
0.74  (16.838) -11.05  (21.725) -8.85  (11.968) 3.03  (19.816) 0.00 -10.80  (21.535)
Change at Cycle 23 Day 1 Number Analyzed 24 participants 34 participants 12 participants 0 participants 0 participants 34 participants
-1.39  (13.157) -5.64  (19.754) -3.47  (18.278) -5.64  (19.754)
Change at Cycle 25 Day 1 Number Analyzed 17 participants 26 participants 7 participants 0 participants 0 participants 26 participants
1.96  (13.349) -7.05  (18.057) -2.38  (19.670) -7.05  (18.057)
Change at End of treatment visit Number Analyzed 2 participants 7 participants 4 participants 4 participants 2 participants 9 participants
0.00  (11.785) 4.76  (28.810) -4.17  (10.758) -6.25  (18.478) 4.17  (29.463) 4.63  (27.039)
29.Secondary Outcome
Title Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Hide Description EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Time Frame Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 166 181 160 231 83 264
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 166 participants 181 participants 160 participants 231 participants 83 participants 264 participants
74.68  (21.233) 74.46  (22.367) 72.31  (24.695) 73.04  (24.450) 74.20  (21.488) 74.38  (22.054)
Change at Cycle 3 Day 1 Number Analyzed 152 participants 156 participants 136 participants 220 participants 70 participants 226 participants
3.23  (20.588) -0.34  (22.138) 1.88  (20.610) 7.29  (20.011) 1.79  (19.958) 0.32  (21.465)
Change at Cycle 5 Day 1 Number Analyzed 134 participants 139 participants 111 participants 205 participants 62 participants 201 participants
5.37  (19.243) 1.54  (22.418) 2.03  (20.662) 6.15  (21.401) 2.96  (20.473) 1.98  (21.796)
Change at Cycle 7 Day 1 Number Analyzed 125 participants 115 participants 85 participants 188 participants 53 participants 168 participants
5.42  (20.027) 0.34  (23.104) 2.71  (20.875) 9.37  (21.088) -3.62  (19.441) -0.91  (22.033)
Change at Cycle 9 Day 1 Number Analyzed 107 participants 88 participants 67 participants 157 participants 42 participants 130 participants
4.47  (24.341) 2.15  (19.735) -0.17  (24.283) 9.22  (21.940) -0.60  (16.296) 1.26  (18.674)
Change at Cycle 11 Day 1 Number Analyzed 93 participants 71 participants 46 participants 147 participants 31 participants 102 participants
4.81  (22.102) 0.12  (22.205) 4.53  (18.148) 10.56  (20.850) -2.69  (17.793) -0.74  (20.915)
Change at Cycle 13 Day 1 Number Analyzed 79 participants 64 participants 37 participants 126 participants 26 participants 90 participants
3.52  (23.715) 3.78  (19.694) -2.25  (22.192) 8.66  (21.894) -6.41  (17.998) 0.83  (19.675)
Change at Cycle 15 Day 1 Number Analyzed 68 participants 58 participants 29 participants 101 participants 17 participants 75 participants
7.35  (21.813) 2.30  (20.755) -5.46  (26.190) 10.59  (19.609) -2.12  (13.232) 1.30  (19.317)
Change at Cycle 17 Day 1 Number Analyzed 61 participants 55 participants 24 participants 64 participants 14 participants 69 participants
5.33  (20.584) 3.64  (21.502) -1.39  (15.862) 10.33  (20.415) 1.79  (15.736) 3.26  (20.373)
Change at Cycle 19 Day 1 Number Analyzed 49 participants 50 participants 22 participants 27 participants 9 participants 59 participants
4.25  (19.552) 1.00  (24.493) 0.38  (16.158) 8.33  (22.997) 2.78  (16.667) 1.27  (23.357)
Change at Cycle 21 Day 1 Number Analyzed 34 participants 43 participants 16 participants 11 participants 1 participants 44 participants
4.17  (19.811) -1.16  (23.751) -3.13  (16.908) 13.13  (15.619) 16.67 -0.76  (23.626)
Change at Cycle 23 Day 1 Number Analyzed 24 participants 34 participants 12 participants 0 participants 0 participants 34 participants
-1.74  (21.420) 2.94  (22.556) -0.69  (23.693) 2.94  (22.556)
Change at Cycle 25 Day 1 Number Analyzed 17 participants 26 participants 7 participants 0 participants 0 participants 26 participants
3.92  (11.456) -0.32  (24.093) -1.19  (34.503) -0.32  (24.093)
Change at End of treatment visit Number Analyzed 2 participants 7 participants 4 participants 4 participants 3 participants 10 participants
41.67  (11.785) -3.57  (25.394) 12.50  (28.464) -4.17  (14.434) 5.56  (4.811) -0.83  (21.318)
30.Secondary Outcome
Title Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Hide Description EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Time Frame Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 167 180 159 235 83 263
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 167 participants 180 participants 159 participants 235 participants 83 participants 263 participants
82.10  (19.593) 83.18  (20.266) 80.71  (22.182) 80.67  (21.889) 81.45  (21.890) 82.63  (20.766)
Change at Cycle 3 Day 1 Number Analyzed 153 participants 157 participants 135 participants 222 participants 70 participants 227 participants
0.20  (18.033) -13.79  (20.396) -2.90  (20.319) 2.94  (16.831) -13.63  (22.428) -13.74  (20.994)
Change at Cycle 5 Day 1 Number Analyzed 135 participants 138 participants 111 participants 208 participants 62 participants 200 participants
0.15  (18.388) -17.14  (22.276) -7.45  (17.792) 2.73  (17.748) -12.63  (21.570) -15.74  (22.104)
Change at Cycle 7 Day 1 Number Analyzed 127 participants 115 participants 84 participants 191 participants 53 participants 168 participants
-1.93  (18.071) -16.26  (21.719) -6.98  (19.605) 1.22  (17.469) -17.01  (20.200) -16.49  (21.194)
Change at Cycle 9 Day 1 Number Analyzed 110 participants 88 participants 66 participants 160 participants 42 participants 130 participants
-0.45  (20.511) -19.43  (20.755) -6.82  (21.881) 3.03  (16.525) -15.83  (16.269) -18.27  (19.429)
Change at Cycle 11 Day 1 Number Analyzed 94 participants 71 participants 45 participants 148 participants 31 participants 102 participants
-0.85  (18.767) -22.65  (20.867) -4.11  (18.680) 0.50  (17.734) -13.49  (13.665) -19.87  (19.369)
Change at Cycle 13 Day 1 Number Analyzed 80 participants 64 participants 36 participants 127 participants 26 participants 90 participants
-1.25  (19.705) -20.00  (20.874) -6.30  (22.534) 0.47  (18.290) -13.85  (17.781) -18.22  (20.127)
Change at Cycle 15 Day 1 Number Analyzed 69 participants 58 participants 30 participants 101 participants 17 participants 75 participants
0.29  (17.356) -20.26  (21.030) -6.22  (21.580) -0.40  (22.466) -24.31  (22.845) -21.18  (21.364)
Change at Cycle 17 Day 1 Number Analyzed 63 participants 55 participants 25 participants 66 participants 14 participants 69 participants
-0.03  (17.862) -18.88  (20.072) -3.27  (19.817) -0.88  (16.432) -19.05  (23.367) -18.91  (20.599)
Change at Cycle 19 Day 1 Number Analyzed 49 participants 49 participants 21 participants 28 participants 9 participants 58 participants
-1.22  (16.140) -20.07  (21.417) -1.90  (20.237) -5.71  (16.301) -14.07  (14.699) -19.14  (20.527)
Change at Cycle 21 Day 1 Number Analyzed 35 participants 43 participants 16 participants 11 participants 1 participants 44 participants
-0.95  (13.150) -16.86  (19.694) -4.90  (19.355) -8.48  (23.303) -13.33 -16.78  (19.471)
Change at Cycle 23 Day 1 Number Analyzed 24 participants 34 participants 12 participants 0 participants 0 participants 34 participants
-5.00  (13.656) -14.46  (18.298) -2.22  (19.557) -14.46  (18.298)
Change at Cycle 25 Day 1 Number Analyzed 17 participants 25 participants 7 participants 0 participants 0 participants 25 participants
-5.49  (14.575) -15.93  (17.092) -4.76  (23.637) -15.93  (17.092)
Change at End of treatment visit Number Analyzed 2 participants 7 participants 4 participants 4 participants 3 participants 10 participants
33.33  (47.140) -0.95  (22.910) -15.00  (19.149) -5.00  (10.000) -4.44  (3.849) -2.00  (18.869)
31.Secondary Outcome
Title Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Hide Description EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Time Frame Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 164 179 160 229 83 262
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 164 participants 179 participants 160 participants 229 participants 83 participants 262 participants
80.69  (24.696) 80.91  (23.841) 78.54  (26.854) 81.37  (25.262) 78.31  (28.600) 80.09  (25.418)
Change at Cycle 3 Day 1 Number Analyzed 152 participants 155 participants 136 participants 218 participants 70 participants 225 participants
-0.66  (27.854) -10.86  (28.967) -4.90  (30.097) 4.05  (22.461) -10.00  (26.829) -10.59  (28.262)
Change at Cycle 5 Day 1 Number Analyzed 133 participants 137 participants 111 participants 203 participants 62 participants 199 participants
3.26  (27.559) -11.92  (32.145) -7.21  (27.026) 3.37  (20.604) -5.11  (28.244) -9.80  (31.073)
Change at Cycle 7 Day 1 Number Analyzed 124 participants 114 participants 85 participants 186 participants 54 participants 168 participants
2.82  (28.807) -9.80  (28.979) -2.75  (31.586) 3.05  (22.185) -13.89  (27.992) -11.11  (28.646)
Change at Cycle 9 Day 1 Number Analyzed 106 participants 87 participants 67 participants 155 participants 42 participants 129 participants
1.57  (31.834) -15.71  (26.579) -1.99  (30.084) 3.66  (21.002) -9.52  (14.790) -13.70  (23.520)
Change at Cycle 11 Day 1 Number Analyzed 92 participants 70 participants 46 participants 145 participants 31 participants 101 participants
-2.72  (29.160) -12.62  (27.428) -0.36  (28.865) 1.95  (23.032) -12.37  (23.161) -12.54  (26.077)
Change at Cycle 13 Day 1 Number Analyzed 78 participants 63 participants 37 participants 124 participants 26 participants 89 participants
-4.27  (28.228) -11.38  (28.053) -0.45  (27.635) 1.75  (24.585) -5.77  (18.822) -9.74  (25.723)
Change at Cycle 15 Day 1 Number Analyzed 67 participants 58 participants 29 participants 99 participants 17 participants 75 participants
3.73  (25.921) -10.63  (27.695) -6.32  (34.622) 2.86  (22.340) -15.69  (16.106) -11.78  (25.524)
Change at Cycle 17 Day 1 Number Analyzed 60 participants 54 participants 24 participants 63 participants 14 participants 68 participants
1.11  (27.251) -11.42  (25.865) 1.39  (25.020) 1.59  (22.543) -7.14  (28.280) -10.54  (26.219)
Change at Cycle 19 Day 1 Number Analyzed 48 participants 50 participants 22 participants 27 participants 9 participants 59 participants
-1.04  (30.248) -12.33  (30.826) 3.79  (26.192) 1.23  (22.133) -12.96  (34.134) -12.43  (31.041)
Change at Cycle 21 Day 1 Number Analyzed 33 participants 43 participants 16 participants 11 participants 1 participants 44 participants
-1.52  (32.103) -14.73  (30.257) -3.13  (22.948) 4.55  (18.395) -33.33 -15.15  (30.034)
Change at Cycle 23 Day 1 Number Analyzed 23 participants 34 participants 12 participants 0 participants 0 participants 34 participants
-12.32  (28.077) -6.37  (20.521) 1.39  (15.006) -6.37  (20.521)
Change at Cycle 25 Day 1 Number Analyzed 16 participants 26 participants 7 participants 0 participants 0 participants 26 participants
-5.21  (23.348) -7.05  (24.117) 4.76  (20.893) -7.05  (24.117)
Change at End of treatment visit Number Analyzed 2 participants 7 participants 4 participants 4 participants 3 participants 10 participants
25.00  (35.355) -19.05  (26.227) -8.33  (9.623) -16.67  (30.429) 0.00  (33.333) -13.33  (28.109)
32.Secondary Outcome
Title Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Hide Description ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead.
Time Frame Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, "Number analyzed" signifies participants evaluable for each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm. Data is reported only for categories with non-zero values.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 192 186 257 84 276
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline: ECOG score 0 Number Analyzed 192 participants 192 participants 186 participants 257 participants 84 participants 276 participants
136
  70.8%
139
  72.4%
135
  72.6%
189
  73.5%
60
  71.4%
199
  72.1%
Baseline: ECOG score 1 Number Analyzed 192 participants 192 participants 186 participants 257 participants 84 participants 276 participants
56
  29.2%
53
  27.6%
51
  27.4%
68
  26.5%
24
  28.6%
77
  27.9%
Cycle 2 Day 1: ECOG score 0 Number Analyzed 188 participants 182 participants 181 participants 256 participants 80 participants 262 participants
142
  75.5%
98
  53.8%
113
  62.4%
193
  75.4%
44
  55.0%
142
  54.2%
Cycle 2 Day 1: ECOG score 1 Number Analyzed 188 participants 182 participants 181 participants 256 participants 80 participants 262 participants
44
  23.4%
79
  43.4%
64
  35.4%
62
  24.2%
32
  40.0%
111
  42.4%
Cycle 2 Day 1: ECOG score 2 Number Analyzed 188 participants 182 participants 181 participants 256 participants 80 participants 262 participants
1
   0.5%
3
   1.6%
4
   2.2%
1
   0.4%
4
   5.0%
7
   2.7%
Cycle 2 Day 1: ECOG score 3 Number Analyzed 188 participants 182 participants 181 participants 256 participants 80 participants 262 participants
0
   0.0%
2
   1.1%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.8%
Cycle 2 Day 1: ECOG score 4 Number Analyzed 188 participants 182 participants 181 participants 256 participants 80 participants 262 participants
1
   0.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 3 Day 1: ECOG score 0 Number Analyzed 185 participants 175 participants 176 participants 253 participants 74 participants 249 participants
131
  70.8%
90
  51.4%
107
  60.8%
197
  77.9%
40
  54.1%
130
  52.2%
Cycle 3 Day 1: ECOG score 1 Number Analyzed 185 participants 175 participants 176 participants 253 participants 74 participants 249 participants
53
  28.6%
81
  46.3%
64
  36.4%
55
  21.7%
32
  43.2%
113
  45.4%
Cycle 3 Day 1: ECOG score 2 Number Analyzed 185 participants 175 participants 176 participants 253 participants 74 participants 249 participants
1
   0.5%
4
   2.3%
4
   2.3%
1
   0.4%
2
   2.7%
6
   2.4%
Cycle 4 Day 1: ECOG score 0 Number Analyzed 179 participants 164 participants 158 participants 250 participants 68 participants 232 participants
128
  71.5%
93
  56.7%
98
  62.0%
189
  75.6%
35
  51.5%
128
  55.2%
Cycle 4 Day 1: ECOG score 1 Number Analyzed 179 participants 164 participants 158 participants 250 participants 68 participants 232 participants
50
  27.9%
66
  40.2%
52
  32.9%
56
  22.4%
30
  44.1%
96
  41.4%
Cycle 4 Day 1: ECOG score 2 Number Analyzed 179 participants 164 participants 158 participants 250 participants 68 participants 232 participants
1
   0.6%
4
   2.4%
4
   2.5%
4
   1.6%
3
   4.4%
7
   3.0%
Cycle 4 Day 1: ECOG score 3 Number Analyzed 179 participants 164 participants 158 participants 250 participants 68 participants 232 participants
0
   0.0%
1
   0.6%
4
   2.5%
1
   0.4%
0
   0.0%
1
   0.4%
Cycle 5 Day 1: ECOG score 0 Number Analyzed 174 participants 158 participants 143 participants 239 participants 66 participants 224 participants
128
  73.6%
85
  53.8%
82
  57.3%
181
  75.7%
33
  50.0%
118
  52.7%
Cycle 5 Day 1: ECOG score 1 Number Analyzed 174 participants 158 participants 143 participants 239 participants 66 participants 224 participants
42
  24.1%
69
  43.7%
52
  36.4%
55
  23.0%
31
  47.0%
100
  44.6%
Cycle 5 Day 1: ECOG score 2 Number Analyzed 174 participants 158 participants 143 participants 239 participants 66 participants 224 participants
3
   1.7%
4
   2.5%
7
   4.9%
2
   0.8%
2
   3.0%
6
   2.7%
Cycle 5 Day 1: ECOG score 3 Number Analyzed 174 participants 158 participants 143 participants 239 participants 66 participants 224 participants
1
   0.6%
0
   0.0%
1
   0.7%
1
   0.4%
0
   0.0%
0
   0.0%
Cycle 5 Day 1: ECOG score 4 Number Analyzed 174 participants 158 participants 143 participants 239 participants 66 participants 224 participants
0
   0.0%
0
   0.0%
1
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 6 Day 1: ECOG score 0 Number Analyzed 169 participants 137 participants 126 participants 231 participants 58 participants 195 participants
124
  73.4%
68
  49.6%
78
  61.9%
168
  72.7%
29
  50.0%
97
  49.7%
Cycle 6 Day 1: ECOG score 1 Number Analyzed 169 participants 137 participants 126 participants 231 participants 58 participants 195 participants
45
  26.6%
65
  47.4%
46
  36.5%
58
  25.1%
25
  43.1%
90
  46.2%
Cycle 6 Day 1: ECOG score 2 Number Analyzed 169 participants 137 participants 126 participants 231 participants 58 participants 195 participants
0
   0.0%
3
   2.2%
1
   0.8%
3
   1.3%
3
   5.2%
6
   3.1%
Cycle 6 Day 1: ECOG score 3 Number Analyzed 169 participants 137 participants 126 participants 231 participants 58 participants 195 participants
0
   0.0%
0
   0.0%
1
   0.8%
1
   0.4%
1
   1.7%
1
   0.5%
Cycle 6 Day 1: ECOG score 4 Number Analyzed 169 participants 137 participants 126 participants 231 participants 58 participants 195 participants
0
   0.0%
1
   0.7%
0
   0.0%
1
   0.4%
0
   0.0%
1
   0.5%
Cycle 7 Day 1: ECOG score 0 Number Analyzed 158 participants 129 participants 111 participants 218 participants 55 participants 184 participants
111
  70.3%
68
  52.7%
74
  66.7%
158
  72.5%
27
  49.1%
95
  51.6%
Cycle 7 Day 1: ECOG score 1 Number Analyzed 158 participants 129 participants 111 participants 218 participants 55 participants 184 participants
46
  29.1%
60
  46.5%
35
  31.5%
58
  26.6%
27
  49.1%
87
  47.3%
Cycle 7 Day 1: ECOG score 2 Number Analyzed 158 participants 129 participants 111 participants 218 participants 55 participants 184 participants
1
   0.6%
1
   0.8%
2
   1.8%
2
   0.9%
1
   1.8%
2
   1.1%
Cycle 8 Day 1: ECOG score 0 Number Analyzed 148 participants 108 participants 95 participants 200 participants 46 participants 154 participants
112
  75.7%
55
  50.9%
58
  61.1%
140
  70.0%
22
  47.8%
77
  50.0%
Cycle 8 Day 1: ECOG score 1 Number Analyzed 148 participants 108 participants 95 participants 200 participants 46 participants 154 participants
33
  22.3%
49
  45.4%
33
  34.7%
58
  29.0%
21
  45.7%
70
  45.5%
Cycle 8 Day 1: ECOG score 2 Number Analyzed 148 participants 108 participants 95 participants 200 participants 46 participants 154 participants
2
   1.4%
3
   2.8%
4
   4.2%
1
   0.5%
3
   6.5%
6
   3.9%
Cycle 8 Day 1: ECOG score 3 Number Analyzed 148 participants 108 participants 95 participants 200 participants 46 participants 154 participants
1
   0.7%
1
   0.9%
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.6%
Cycle 9 Day 1: ECOG score 0 Number Analyzed 144 participants 98 participants 90 participants 188 participants 43 participants 141 participants
102
  70.8%
50
  51.0%
55
  61.1%
135
  71.8%
22
  51.2%
72
  51.1%
Cycle 9 Day 1: ECOG score 1 Number Analyzed 144 participants 98 participants 90 participants 188 participants 43 participants 141 participants
36
  25.0%
47
  48.0%
30
  33.3%
52
  27.7%
20
  46.5%
67
  47.5%
Cycle 9 Day 1: ECOG score 2 Number Analyzed 144 participants 98 participants 90 participants 188 participants 43 participants 141 participants
4
   2.8%
1
   1.0%
4
   4.4%
0
   0.0%
0
   0.0%
1
   0.7%
Cycle 9 Day 1: ECOG score 3 Number Analyzed 144 participants 98 participants 90 participants 188 participants 43 participants 141 participants
0
   0.0%
0
   0.0%
1
   1.1%
0
   0.0%
1
   2.3%
1
   0.7%
Cycle 9 Day 1: ECOG score 4 Number Analyzed 144 participants 98 participants 90 participants 188 participants 43 participants 141 participants
1
   0.7%
0
   0.0%
0
   0.0%
1
   0.5%
0
   0.0%
0
   0.0%
Cycle 9 Day 1: ECOG score 5 Number Analyzed 144 participants 98 participants 90 participants 188 participants 43 participants 141 participants
1
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 10 Day 1: ECOG score 0 Number Analyzed 129 participants 88 participants 72 participants 171 participants 37 participants 125 participants
94
  72.9%
52
  59.1%
43
  59.7%
121
  70.8%
18
  48.6%
70
  56.0%
Cycle 10 Day 1: ECOG score 1 Number Analyzed 129 participants 88 participants 72 participants 171 participants 37 participants 125 participants
32
  24.8%
35
  39.8%
26
  36.1%
46
  26.9%
18
  48.6%
53
  42.4%
Cycle 10 Day 1: ECOG score 2 Number Analyzed 129 participants 88 participants 72 participants 171 participants 37 participants 125 participants
3
   2.3%
1
   1.1%
2
   2.8%
3
   1.8%
1
   2.7%
2
   1.6%
Cycle 10 Day 1: ECOG score 3 Number Analyzed 129 participants 88 participants 72 participants 171 participants 37 participants 125 participants
0
   0.0%
0
   0.0%
1
   1.4%
1
   0.6%
0
   0.0%
0
   0.0%
Cycle 11 Day 1: ECOG score 0 Number Analyzed 120 participants 85 participants 62 participants 158 participants 36 participants 121 participants
88
  73.3%
44
  51.8%
39
  62.9%
116
  73.4%
17
  47.2%
61
  50.4%
Cycle 11 Day 1: ECOG score 1 Number Analyzed 120 participants 85 participants 62 participants 158 participants 36 participants 121 participants
30
  25.0%
40
  47.1%
20
  32.3%
42
  26.6%
16
  44.4%
56
  46.3%
Cycle 11 Day 1: ECOG score 2 Number Analyzed 120 participants 85 participants 62 participants 158 participants 36 participants 121 participants
2
   1.7%
1
   1.2%
2
   3.2%
0
   0.0%
3
   8.3%
4
   3.3%
Cycle 11 Day 1: ECOG score 3 Number Analyzed 120 participants 85 participants 62 participants 158 participants 36 participants 121 participants
0
   0.0%
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 12 Day 1: ECOG score 0 Number Analyzed 110 participants 77 participants 51 participants 152 participants 30 participants 107 participants
84
  76.4%
44
  57.1%
32
  62.7%
113
  74.3%
11
  36.7%
55
  51.4%
Cycle 12 Day 1: ECOG score 1 Number Analyzed 110 participants 77 participants 51 participants 152 participants 30 participants 107 participants
25
  22.7%
31
  40.3%
16
  31.4%
38
  25.0%
18
  60.0%
49
  45.8%
Cycle 12 Day 1: ECOG score 2 Number Analyzed 110 participants 77 participants 51 participants 152 participants 30 participants 107 participants
1
   0.9%
1
   1.3%
2
   3.9%
0
   0.0%
1
   3.3%
2
   1.9%
Cycle 12 Day 1: ECOG score 3 Number Analyzed 110 participants 77 participants 51 participants 152 participants 30 participants 107 participants
0
   0.0%
1
   1.3%
1
   2.0%
0
   0.0%
0
   0.0%
1
   0.9%
Cycle 12 Day 1: ECOG score 4 Number Analyzed 110 participants 77 participants 51 participants 152 participants 30 participants 107 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.7%
0
   0.0%
0
   0.0%
Cycle 13 Day 1: ECOG score 0 Number Analyzed 100 participants 73 participants 47 participants 143 participants 31 participants 104 participants
77
  77.0%
41
  56.2%
27
  57.4%
102
  71.3%
14
  45.2%
55
  52.9%
Cycle 13 Day 1: ECOG score 1 Number Analyzed 100 participants 73 participants 47 participants 143 participants 31 participants 104 participants
22
  22.0%
31
  42.5%
18
  38.3%
39
  27.3%
15
  48.4%
46
  44.2%
Cycle 13 Day 1: ECOG score 2 Number Analyzed 100 participants 73 participants 47 participants 143 participants 31 participants 104 participants
1
   1.0%
1
   1.4%
2
   4.3%
1
   0.7%
2
   6.5%
3
   2.9%
Cycle 13 Day 1: ECOG score 4 Number Analyzed 100 participants 73 participants 47 participants 143 participants 31 participants 104 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.7%
0
   0.0%
0
   0.0%
Cycle 14 Day 1: ECOG score 0 Number Analyzed 97 participants 75 participants 46 participants 136 participants 27 participants 102 participants
74
  76.3%
47
  62.7%
25
  54.3%
100
  73.5%
15
  55.6%
62
  60.8%
Cycle 14 Day 1: ECOG score 1 Number Analyzed 97 participants 75 participants 46 participants 136 participants 27 participants 102 participants
23
  23.7%
27
  36.0%
19
  41.3%
33
  24.3%
10
  37.0%
37
  36.3%
Cycle 14 Day 1: ECOG score 2 Number Analyzed 97 participants 75 participants 46 participants 136 participants 27 participants 102 participants
0
   0.0%
0
   0.0%
2
   4.3%
2
   1.5%
2
   7.4%
2
   2.0%
Cycle 14 Day 1: ECOG score 3 Number Analyzed 97 participants 75 participants 46 participants 136 participants 27 participants 102 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.7%
0
   0.0%
0
   0.0%
Cycle 14 Day 1: ECOG score 4 Number Analyzed 97 participants 75 participants 46 participants 136 participants 27 participants 102 participants
0
   0.0%
1
   1.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.0%
Cycle 15 Day 1: ECOG score 0 Number Analyzed 94 participants 72 participants 41 participants 111 participants 21 participants 93 participants
72
  76.6%
41
  56.9%
22
  53.7%
82
  73.9%
13
  61.9%
54
  58.1%
Cycle 15 Day 1: ECOG score 1 Number Analyzed 94 participants 72 participants 41 participants 111 participants 21 participants 93 participants
20
  21.3%
30
  41.7%
18
  43.9%
27
  24.3%
7
  33.3%
37
  39.8%
Cycle 15 Day 1: ECOG score 2 Number Analyzed 94 participants 72 participants 41 participants 111 participants 21 participants 93 participants
1
   1.1%
1
   1.4%
1
   2.4%
1
   0.9%
1
   4.8%
2
   2.2%
Cycle 15 Day 1: ECOG score 3 Number Analyzed 94 participants 72 participants 41 participants 111 participants 21 participants 93 participants
1
   1.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 15 Day 1: ECOG score 4 Number Analyzed 94 participants 72 participants 41 participants 111 participants 21 participants 93 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.9%
0
   0.0%
0
   0.0%
Cycle 16 Day 1: ECOG score 0 Number Analyzed 89 participants 67 participants 35 participants 88 participants 19 participants 86 participants
64
  71.9%
41
  61.2%
24
  68.6%
64
  72.7%
11
  57.9%
52
  60.5%
Cycle 16 Day 1: ECOG score 1 Number Analyzed 89 participants 67 participants 35 participants 88 participants 19 participants 86 participants
24
  27.0%
23
  34.3%
10
  28.6%
23
  26.1%
7
  36.8%
30
  34.9%
Cycle 16 Day 1: ECOG score 2 Number Analyzed 89 participants 67 participants 35 participants 88 participants 19 participants 86 participants
1
   1.1%
3
   4.5%
1
   2.9%
0
   0.0%
1
   5.3%
4
   4.7%
Cycle 16 Day 1: ECOG score 3 Number Analyzed 89 participants 67 participants 35 participants 88 participants 19 participants 86 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
0
   0.0%
0
   0.0%
Cycle 17 Day 1: ECOG score 0 Number Analyzed 82 participants 67 participants 33 participants 68 participants 16 participants 83 participants
65
  79.3%
39
  58.2%
21
  63.6%
52
  76.5%
9
  56.3%
48
  57.8%
Cycle 17 Day 1: ECOG score 1 Number Analyzed 82 participants 67 participants 33 participants 68 participants 16 participants 83 participants
16
  19.5%
27
  40.3%
11
  33.3%
15
  22.1%
6
  37.5%
33
  39.8%
Cycle 17 Day 1: ECOG score 2 Number Analyzed 82 participants 67 participants 33 participants 68 participants 16 participants 83 participants
1
   1.2%
1
   1.5%
1
   3.0%
1
   1.5%
1
   6.3%
2
   2.4%
Cycle 18 Day 1: ECOG score 0 Number Analyzed 75 participants 60 participants 31 participants 46 participants 10 participants 70 participants
60
  80.0%
36
  60.0%
18
  58.1%
34
  73.9%
5
  50.0%
41
  58.6%
Cycle 18 Day 1: ECOG score 1 Number Analyzed 75 participants 60 participants 31 participants 46 participants 10 participants 70 participants
14
  18.7%
24
  40.0%
11
  35.5%
11
  23.9%
5
  50.0%
29
  41.4%
Cycle 18 Day 1: ECOG score 2 Number Analyzed 75 participants 60 participants 31 participants 46 participants 10 participants 70 participants
1
   1.3%
0
   0.0%
1
   3.2%
1
   2.2%
0
   0.0%
0
   0.0%
Cycle 18 Day 1: ECOG score 3 Number Analyzed 75 participants 60 participants 31 participants 46 participants 10 participants 70 participants
0
   0.0%
0
   0.0%
1
   3.2%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 19 Day 1: ECOG score 0 Number Analyzed 65 participants 59 participants 30 participants 30 participants 8 participants 67 participants
54
  83.1%
38
  64.4%
20
  66.7%
22
  73.3%
2
  25.0%
40
  59.7%
Cycle 19 Day 1: ECOG score 1 Number Analyzed 65 participants 59 participants 30 participants 30 participants 8 participants 67 participants
9
  13.8%
20
  33.9%
9
  30.0%
7
  23.3%
6
  75.0%
26
  38.8%
Cycle 19 Day 1: ECOG score 2 Number Analyzed 65 participants 59 participants 30 participants 30 participants 8 participants 67 participants
2
   3.1%
1
   1.7%
1
   3.3%
1
   3.3%
0
   0.0%
1
   1.5%
Cycle 20 Day 1: ECOG score 0 Number Analyzed 61 participants 52 participants 27 participants 20 participants 6 participants 58 participants
53
  86.9%
31
  59.6%
19
  70.4%
15
  75.0%
3
  50.0%
34
  58.6%
Cycle 20 Day 1: ECOG score 1 Number Analyzed 61 participants 52 participants 27 participants 20 participants 6 participants 58 participants
7
  11.5%
19
  36.5%
8
  29.6%
5
  25.0%
3
  50.0%
22
  37.9%
Cycle 20 Day 1: ECOG score 2 Number Analyzed 61 participants 52 participants 27 participants 20 participants 6 participants 58 participants
0
   0.0%
2
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
2
   3.4%
Cycle 20 Day 1: ECOG score 3 Number Analyzed 61 participants 52 participants 27 participants 20 participants 6 participants 58 participants
1
   1.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Cycle 21 Day 1: ECOG score 0 Number Analyzed 46 participants 49 participants 23 participants 13 participants 3 participants 52 participants
36
  78.3%
29
  59.2%
15
  65.2%
11
  84.6%
2
  66.7%
31
  59.6%
Cycle 21 Day 1: ECOG score 1 Number Analyzed 46 participants 49 participants 23 participants 13 participants 3 participants 52 participants
10
  21.7%
19
  38.8%
8
  34.8%
2
  15.4%
1
  33.3%
20
  38.5%
Cycle 21 Day 1: ECOG score 2 Number Analyzed 46 participants 49 participants 23 participants 13 participants 3 participants 52 participants
9
  19.6%
1
   2.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.9%
Cycle 22 Day 1: ECOG score 0 Number Analyzed 37 participants 45 participants 17 participants 6 participants 0 participants 45 participants
29
  78.4%
27
  60.0%
11
  64.7%
4
  66.7%
 0
27
  60.0%
Cycle 22 Day 1: ECOG score 1 Number Analyzed 37 participants 45 participants 17 participants 6 participants 0 participants 45 participants
8
  21.6%
16
  35.6%
6
  35.3%
2
  33.3%
 0
16
  35.6%
Cycle 22 Day 1: ECOG score 3 Number Analyzed 37 participants 45 participants 17 participants 6 participants 0 participants 45 participants
0
   0.0%
1
   2.2%
0
   0.0%
0
   0.0%
 0
1
   2.2%
Cycle 22 Day 1: ECOG score 4 Number Analyzed 37 participants 45 participants 17 participants 6 participants 0 participants 45 participants
0
   0.0%
1
   2.2%
0
   0.0%
0
   0.0%
 0
1
   2.2%
Cycle 23 Day 1: ECOG score 0 Number Analyzed 30 participants 38 participants 15 participants 0 participants 0 participants 38 participants
24
  80.0%
26
  68.4%
10
  66.7%
 0 0
26
  68.4%
Cycle 23 Day 1: ECOG score 1 Number Analyzed 30 participants 38 participants 15 participants 0 participants 0 participants 38 participants
6
  20.0%
12
  31.6%
5
  33.3%
 0 0
12
  31.6%
Cycle 24 Day 1: ECOG score 0 Number Analyzed 28 participants 33 participants 14 participants 0 participants 0 participants 33 participants
21
  75.0%
23
  69.7%
9
  64.3%
 0 0
23
  69.7%
Cycle 24 Day 1: ECOG score 1 Number Analyzed 28 participants 33 participants 14 participants 0 participants 0 participants 33 participants
7
  25.0%
10
  30.3%
5
  35.7%
 0 0
10
  30.3%
Cycle 25 Day 1: ECOG score 0 Number Analyzed 20 participants 31 participants 11 participants 0 participants 0 participants 31 participants
17
  85.0%
23
  74.2%
9
  81.8%
 0 0
23
  74.2%
Cycle 25 Day 1: ECOG score 1 Number Analyzed 20 participants 31 participants 11 participants 0 participants 0 participants 31 participants
3
  15.0%
8
  25.8%
2
  18.2%
 0 0
8
  25.8%
Cycle 26 Day 1: ECOG score 0 Number Analyzed 18 participants 29 participants 9 participants 0 participants 0 participants 29 participants
14
  77.8%
21
  72.4%
7
  77.8%
 0 0
21
  72.4%
Cycle 26 Day 1: ECOG score 1 Number Analyzed 18 participants 29 participants 9 participants 0 participants 0 participants 29 participants
3
  16.7%
8
  27.6%
2
  22.2%
 0 0
8
  27.6%
Cycle 26 Day 1: ECOG score 2 Number Analyzed 18 participants 29 participants 9 participants 0 participants 0 participants 29 participants
1
   5.6%
0
   0.0%
0
   0.0%
 0 0
0
   0.0%
Cycle 27 Day 1: ECOG score 0 Number Analyzed 8 participants 26 participants 7 participants 0 participants 0 participants 26 participants
5
  62.5%
20
  76.9%
3
  42.9%
 0 0
20
  76.9%
Cycle 27 Day 1: ECOG score 1 Number Analyzed 8 participants 26 participants 7 participants 0 participants 0 participants 26 participants
3
  37.5%
6
  23.1%
4
  57.1%
 0 0
6
  23.1%
Cycle 28 Day 1: ECOG score 0 Number Analyzed 8 participants 24 participants 5 participants 0 participants 0 participants 24 participants
5
  62.5%
18
  75.0%
4
  80.0%
 0 0
18
  75.0%
Cycle 28 Day 1: ECOG score 1 Number Analyzed 8 participants 24 participants 5 participants 0 participants 0 participants 24 participants
3
  37.5%
6
  25.0%
1
  20.0%
 0 0
6
  25.0%
Cycle 29 Day 1: ECOG score 0 Number Analyzed 3 participants 18 participants 5 participants 0 participants 0 participants 18 participants
1
  33.3%
13
  72.2%
5
 100.0%
 0 0
13
  72.2%
Cycle 29 Day 1: ECOG score 1 Number Analyzed 3 participants 18 participants 5 participants 0 participants 0 participants 18 participants
2
  66.7%
5
  27.8%
0
   0.0%
 0 0
5
  27.8%
Cycle 30 Day 1: ECOG score 0 Number Analyzed 0 participants 12 participants 4 participants 0 participants 0 participants 12 participants
0
9
  75.0%
4
 100.0%
 0 0
9
  75.0%
Cycle 30 Day 1: ECOG score 1 Number Analyzed 0 participants 12 participants 4 participants 0 participants 0 participants 12 participants
0
3
  25.0%
0
   0.0%
 0 0
3
  25.0%
Cycle 31 Day 1: ECOG score 0 Number Analyzed 0 participants 10 participants 2 participants 0 participants 0 participants 10 participants
0
7
  70.0%
2
 100.0%
 0 0
7
  70.0%
Cycle 31 Day 1: ECOG score 1 Number Analyzed 0 participants 10 participants 2 participants 0 participants 0 participants 10 participants
0
3
  30.0%
0
   0.0%
 0 0
3
  30.0%
33.Secondary Outcome
Title Part 1: Plasma Concentrations of LGX 818
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified row.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 175 172
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Cycle 1 Day 1: pre-dose Number Analyzed 175 participants 172 participants
18.6  (125) 58.1  (513)
Cycle 1 Day 1: 0.5 hours post dose Number Analyzed 159 participants 145 participants
1640  (2400) 1190  (1790)
Cycle 1 Day 1: 1.5 hours post dose Number Analyzed 122 participants 116 participants
6860  (3680) 4090  (2100)
Cycle 1 Day 1: 4 to 8 hours post dose Number Analyzed 147 participants 142 participants
3400  (2010) 1850  (925)
Cycle 2 Day 1: pre-dose Number Analyzed 119 participants 73 participants
119  (468) 73.6  (405)
Cycle 3 Day 1: pre-dose Number Analyzed 98 participants 74 participants
150  (697) 53.8  (256)
34.Secondary Outcome
Title Part 2: Plasma Concentrations of LGX 818
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, "Overall Number of Participants Analyzed" =number of participants evaluable for this outcome measure and "Number analyzed" =participants evaluable at each specified row. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 242 80 252
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Cycle 1 Day 1: pre-dose Number Analyzed 242 participants 80 participants 252 participants
5.02  (77.8) 0.0145  (0.130) 39.7  (424)
Cycle 1 Day 1: 0.5 hours post dose Number Analyzed 207 participants 68 participants 213 participants
1360  (2000) 1370  (2170) 1250  (1910)
Cycle 1 Day 1: 1.5 hours post dose Number Analyzed 220 participants 73 participants 189 participants
4390  (2380) 4310  (2570) 4170  (2290)
Cycle 1 Day 1: 4 to 8 hours post dose Number Analyzed 185 participants 66 participants 208 participants
2420  (1270) 2250  (1170) 1980  (1020)
Cycle 2 Day 1: pre-dose Number Analyzed 175 participants 32 participants 105 participants
121  (483) 29.5  (99.9) 60.1  (342)
Cycle 3 Day 1: pre-dose Number Analyzed 151 participants 27 participants 101 participants
74.1  (322) 79.5  (291) 60.6  (265)
35.Secondary Outcome
Title Part 1: Plasma Concentrations of MEK162
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified row.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 167
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Cycle 1 Day 1: pre-dose Number Analyzed 167 participants
2.95  (30.7)
Cycle 1 Day 1: 0.5 hours post dose Number Analyzed 151 participants
426  (410)
Cycle 1 Day 1: 1.5 hours post dose Number Analyzed 117 participants
832  (527)
Cycle 1 Day 1: 4 to 8 hours post dose Number Analyzed 138 participants
330  (226)
Cycle 2 Day 1: pre-dose Number Analyzed 77 participants
81.0  (106)
Cycle 3 Day 1: pre-dose Number Analyzed 65 participants
68.1  (101)
36.Secondary Outcome
Title Part 2: Plasma Concentrations of MEK162
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set included all participants who received at least one dose of LGX818 or MEK162 and had at least one evaluable post-baseline LGX818 or MEK162 concentration measurement. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure and "Number analyzed" signifies participants evaluable for each specified category at each specified row.
Arm/Group Title Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)
Hide Arm/Group Description:
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 215
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Cycle 1 Day 1: pre-dose Number Analyzed 215 participants
1.68  (24.3)
Cycle 1 Day 1: 0.5 hours post dose Number Analyzed 191 participants
366  (347)
Cycle 1 Day 1: 1.5 hours post dose Number Analyzed 196 participants
642  (337)
Cycle 1 Day 1: 4 to 8 hours post dose Number Analyzed 169 participants
287  (175)
Cycle 2 Day 1: pre-dose Number Analyzed 98 participants
72.3  (62.6)
Cycle 3 Day 1: pre-dose Number Analyzed 94 participants
73.2  (89.0)
37.Secondary Outcome
Title Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Hide Description ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement.
Time Frame Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set includes all participants who received at least one dose of study medication and have at least one valid post-baseline safety evaluation. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure. It was planned to report combined result data of Part 1 and Part 2 for LGX818 300 mg arm.
Arm/Group Title Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg Part 1 + Part 2: LGX818 300 mg
Hide Arm/Group Description:
Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
Participants of Part 1 and 2 received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, and study discontinuation, lost to follow-up or death.
Overall Number of Participants Analyzed 192 187 185 257 83 270
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(23.0 to NA)
26.7 [2] 
(14.8 to NA)
18.2 [2] 
(11.1 to NA)
NA [3] 
(NA to NA)
10.2 [2] 
(8.1 to NA)
19.2 [2] 
(12.9 to NA)
[1]
Median and upper limit of 95% CI were not estimable due to low number of participants with events.
[2]
Upper limit of 95% CI was not estimable due to low number of participants with events.
[3]
Median and 95% CI were not estimable due to low number of participants with events.
Time Frame Part 1: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)
Adverse Event Reporting Description Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis population evaluated.
 
Arm/Group Title Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg
Hide Arm/Group Description Participants received 450 milligram (mg) of LGX818 orally once daily (QD) along with 45 mg of MEK162 twice daily (BID) for each 28 day treatment cycle until progressive disease (PD) as confirmed by Blinded Independent Review Committee (BIRC), withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 960 mg of LGX818 according to the locally approved prescribing information twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily along with 45 mg of MEK162 twice daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death. Participants received 300 mg of LGX818 orally once daily for each 28 day treatment cycle until PD as confirmed by BIRC, withdrawal of consent, intolerable toxicity, study discontinuation, lost to follow-up or death.
All-Cause Mortality
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/192 (34.38%)   67/192 (34.90%)   69/186 (37.10%)   75/257 (29.18%)   25/84 (29.76%) 
Blood and lymphatic system disorders           
Anaemia * 1  4/192 (2.08%)  2/192 (1.04%)  2/186 (1.08%)  4/257 (1.56%)  0/84 (0.00%) 
Thrombocytopenia * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Lymphopenia * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Cardiac disorders           
Myocardial Infarction * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  3/257 (1.17%)  0/84 (0.00%) 
Atrial Fibrillation * 1  1/192 (0.52%)  1/192 (0.52%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Atrioventricular Block First Degree * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Bundle Branch Block Left * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Acute Coronary Syndrome * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Acute Myocardial Infarction * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Left Ventricular Failure * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Myocardial Ischaemia * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Palpitations * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Pericardial Effusion * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  1/84 (1.19%) 
Tachycardia * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Cardio-Respiratory Arrest * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  2/257 (0.78%)  0/84 (0.00%) 
Pericarditis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Cardiac Failure * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Cardiac Tamponade * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Tachyarrhythmia * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Congenital, familial and genetic disorders           
Hydrocele * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Eye disorders           
Chorioretinopathy * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Retinal Detachment * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Normal Tension Glaucoma * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Retinal Artery Occlusion * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Visual Acuity Reduced * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Uveitis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  3/257 (1.17%)  0/84 (0.00%) 
Glaucoma * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Retinal Vein Occlusion * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Gastrointestinal disorders           
Abdominal Pain * 1  4/192 (2.08%)  2/192 (1.04%)  1/186 (0.54%)  1/257 (0.39%)  2/84 (2.38%) 
Vomiting * 1  3/192 (1.56%)  6/192 (3.13%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Abdominal Pain Upper * 1  2/192 (1.04%)  2/192 (1.04%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Colitis * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Nausea * 1  2/192 (1.04%)  6/192 (3.13%)  0/186 (0.00%)  2/257 (0.78%)  0/84 (0.00%) 
Diarrhoea * 1  1/192 (0.52%)  1/192 (0.52%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Enterocolitis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Gastric Ulcer Haemorrhage * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Gastrointestinal Haemorrhage * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Inguinal Hernia * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Pancreatitis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Pancreatitis Acute * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Rectal Haemorrhage * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Subileus * 1  1/192 (0.52%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Abdominal Distension * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Anal Fistula * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Anal Incontinence * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Ascites * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  2/257 (0.78%)  0/84 (0.00%) 
Diarrhoea Haemorrhagic * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Ileus * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Intestinal Obstruction * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Large Intestine Perforation * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Lower Gastrointestinal Haemorrhage * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Upper Gastrointestinal Haemorrhage * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Constipation * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Oesophagitis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Gastritis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
General disorders           
Pyrexia * 1  6/192 (3.13%)  3/192 (1.56%)  2/186 (1.08%)  2/257 (0.78%)  0/84 (0.00%) 
General Physical Health Deterioration * 1  3/192 (1.56%)  2/192 (1.04%)  6/186 (3.23%)  4/257 (1.56%)  1/84 (1.19%) 
Death * 1  2/192 (1.04%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Non-Cardiac Chest Pain * 1  2/192 (1.04%)  2/192 (1.04%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Asthenia * 1  1/192 (0.52%)  2/192 (1.04%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Fatigue * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Inflammation * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Multiple Organ Dysfunction Syndrome * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Pain * 1  1/192 (0.52%)  4/192 (2.08%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Gait Disturbance * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Malaise * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Oedema Peripheral * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Performance Status Decreased * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Hepatobiliary disorders           
Jaundice * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Cholecystitis * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Hepatotoxicity * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Immune system disorders           
Contrast Media Allergy * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Drug Hypersensitivity * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Hypersensitivity * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Infections and infestations           
Pneumonia * 1  3/192 (1.56%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Cellulitis * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  2/257 (0.78%)  0/84 (0.00%) 
Erysipelas * 1  2/192 (1.04%)  1/192 (0.52%)  0/186 (0.00%)  3/257 (1.17%)  0/84 (0.00%) 
Urinary Tract Infection * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Campylobacter Gastroenteritis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Cellulitis Streptococcal * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Chorioretinitis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Diverticulitis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Encephalitis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Gastroenteritis * 1  1/192 (0.52%)  2/192 (1.04%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Herpes Zoster * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Infection * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Pyelonephritis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Urosepsis * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Escherichia Sepsis * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Infected Seroma * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Intestinal Sepsis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Lung Infection * 1  0/192 (0.00%)  0/192 (0.00%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Peritonsillar Abscess * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Respiratory Tract Infection * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Sepsis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  2/257 (0.78%)  0/84 (0.00%) 
Staphylococcal Infection * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Streptococcal Sepsis * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Appendicitis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Clostridium Difficile Colitis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Flavivirus Infection * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Liver Abscess * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Myelitis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Skin Infection * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Nasopharyngitis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Peritoneal Abscess * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Injury, poisoning and procedural complications           
Femur Fracture * 1  1/192 (0.52%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Overdose * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Multiple Injuries * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Radiation Necrosis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Acetabulum Fracture * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Fall * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Seroma * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Spinal Fracture * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Compression Fracture * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Spinal Compression Fracture * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Investigations           
Blood Creatinine Increased * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
C-Reactive Protein Increased * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Gamma-Glutamyltransferase Increased * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Hepatic Enzyme Increased * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Intraocular Pressure Increased * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Lipase Increased * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Lymph Node Palpable * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Myocardial Necrosis Marker Increased * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
White Blood Cell Count Increased * 1  0/192 (0.00%)  0/192 (0.00%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Anticoagulation Drug Level Increased * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Troponin Increased * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Metabolism and nutrition disorders           
Dehydration * 1  1/192 (0.52%)  2/192 (1.04%)  1/186 (0.54%)  2/257 (0.78%)  0/84 (0.00%) 
Hyperkalaemia * 1  1/192 (0.52%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Decreased Appetite * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Hypercalcaemia * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Hyperglycaemia * 1  0/192 (0.00%)  3/192 (1.56%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Hyperlipidaemia * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Hypoglycaemia * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Hyponatraemia * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  1/84 (1.19%) 
Musculoskeletal and connective tissue disorders           
Fracture Pain * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Intervertebral Disc Disorder * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Myositis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Pain In Extremity * 1  1/192 (0.52%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  2/84 (2.38%) 
Rhabdomyolysis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Arthralgia * 1  0/192 (0.00%)  1/192 (0.52%)  3/186 (1.61%)  1/257 (0.39%)  3/84 (3.57%) 
Arthritis * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Back Pain * 1  0/192 (0.00%)  4/192 (2.08%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Groin Pain * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Mobility Decreased * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Musculoskeletal Pain * 1  0/192 (0.00%)  3/192 (1.56%)  1/186 (0.54%)  0/257 (0.00%)  1/84 (1.19%) 
Myalgia * 1  0/192 (0.00%)  3/192 (1.56%)  0/186 (0.00%)  1/257 (0.39%)  1/84 (1.19%) 
Spinal Pain * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Muscular Weakness * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  1/84 (1.19%) 
Polymyalgia Rheumatica * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Rheumatoid Arthritis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Spinal Column Stenosis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Neck Pain * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Intracranial Tumour Haemorrhage * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Metastases To Bone * 1  1/192 (0.52%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Metastases To Central Nervous System * 1  1/192 (0.52%)  3/192 (1.56%)  2/186 (1.08%)  3/257 (1.17%)  1/84 (1.19%) 
Metastases To Meninges * 1  1/192 (0.52%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Rectal Adenocarcinoma * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Basal Cell Carcinoma * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Cancer Pain * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Dermatofibrosarcoma Protuberans * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Malignant Melanoma * 1  0/192 (0.00%)  2/192 (1.04%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Malignant Melanoma In Situ * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Metastases To Adrenals * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Metastasis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Metastatic Malignant Melanoma * 1  0/192 (0.00%)  0/192 (0.00%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Neoplasm * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Squamous Cell Carcinoma * 1  0/192 (0.00%)  0/192 (0.00%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Superficial Spreading Melanoma Stage Unspecified * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Transitional Cell Carcinoma * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Tumour Haemorrhage * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Metastases To Bladder * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Metastases To Spine * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Plasma Cell Myeloma * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Tumour Pain * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Tumour Associated Fever * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Nervous system disorders           
Cerebral Haemorrhage * 1  3/192 (1.56%)  2/192 (1.04%)  1/186 (0.54%)  0/257 (0.00%)  1/84 (1.19%) 
Balance Disorder * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Dizziness * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Transient Ischaemic Attack * 1  2/192 (1.04%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Cervicobrachial Syndrome * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Coma * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Dysarthria * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Epilepsy * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  2/257 (0.78%)  1/84 (1.19%) 
Headache * 1  1/192 (0.52%)  1/192 (0.52%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Hemiparesis * 1  1/192 (0.52%)  2/192 (1.04%)  3/186 (1.61%)  1/257 (0.39%)  0/84 (0.00%) 
Somnolence * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Spinal Cord Compression * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Syncope * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  2/257 (0.78%)  0/84 (0.00%) 
Brain Oedema * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Brain Stem Syndrome * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Facial Paralysis * 1  0/192 (0.00%)  3/192 (1.56%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Facial Paresis * 1  0/192 (0.00%)  2/192 (1.04%)  0/186 (0.00%)  0/257 (0.00%)  2/84 (2.38%) 
Glial Scar * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Intercostal Neuralgia * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Intracranial Pressure Increased * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Nervous System Disorder * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Paraesthesia * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Paraparesis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Polyneuropathy * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Restless Legs Syndrome * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Seizure * 1  0/192 (0.00%)  1/192 (0.52%)  1/186 (0.54%)  4/257 (1.56%)  0/84 (0.00%) 
Aphasia * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Cerebellar Ischaemia * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Depressed Level Of Consciousness * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Facial Nerve Disorder * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Guillain-Barre Syndrome * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Hypertensive Encephalopathy * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Ischaemic Stroke * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Paresis Cranial Nerve * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Speech Disorder * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Subarachnoid Haemorrhage * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Tremor * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Vertebral Artery Dissection * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Cerebrovascular Accident * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Diplegia * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Monoplegia * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Motor Dysfunction * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Product Issues           
Device Failure * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Psychiatric disorders           
Completed Suicide * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Depression Suicidal * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Mental Status Changes * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Confusional State * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Agitation * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Post-Traumatic Stress Disorder * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Depression * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Renal and urinary disorders           
Acute Kidney Injury * 1  3/192 (1.56%)  1/192 (0.52%)  1/186 (0.54%)  2/257 (0.78%)  3/84 (3.57%) 
Calculus Urethral * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Renal Failure * 1  1/192 (0.52%)  2/192 (1.04%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Renal Impairment * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  1/257 (0.39%)  0/84 (0.00%) 
Ureterolithiasis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Urinary Tract Disorder * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Ureteric Obstruction * 1  0/192 (0.00%)  0/192 (0.00%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Urinary Incontinence * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Urinary Retention * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Reproductive system and breast disorders           
Breast Pain * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pulmonary Embolism * 1  3/192 (1.56%)  0/192 (0.00%)  2/186 (1.08%)  2/257 (0.78%)  0/84 (0.00%) 
Pleural Effusion * 1  2/192 (1.04%)  1/192 (0.52%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Cough * 1  1/192 (0.52%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Dyspnoea * 1  1/192 (0.52%)  1/192 (0.52%)  3/186 (1.61%)  0/257 (0.00%)  0/84 (0.00%) 
Mediastinal Shift * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Epistaxis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Lung Infiltration * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Pleurisy * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Pulmonary Alveolar Haemorrhage * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Respiratory Arrest * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Respiratory Failure * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Pneumothorax * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  1/84 (1.19%) 
Skin and subcutaneous tissue disorders           
Angioedema * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Rash * 1  1/192 (0.52%)  0/192 (0.00%)  2/186 (1.08%)  0/257 (0.00%)  0/84 (0.00%) 
Cutaneous Vasculitis * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Dermatitis Allergic * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Dermatitis Bullous * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Drug Eruption * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Erythema Nodosum * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Granuloma Annulare * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Rash Erythematous * 1  0/192 (0.00%)  1/192 (0.52%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Rash Generalised * 1  0/192 (0.00%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Urticaria * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Vascular disorders           
Deep Vein Thrombosis * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Embolism * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Thrombophlebitis Superficial * 1  1/192 (0.52%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  0/84 (0.00%) 
Circulatory Collapse * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Hypertension * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
Thrombosis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  1/257 (0.39%)  0/84 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) Part 1: LGX818 300 mg Part 1: Vemurafenib 960 mg BID Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) Part 2: LGX818 300 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   189/192 (98.44%)   190/192 (98.96%)   184/186 (98.92%)   251/257 (97.67%)   81/84 (96.43%) 
Blood and lymphatic system disorders           
Anaemia * 1  29/192 (15.10%)  11/192 (5.73%)  14/186 (7.53%)  23/257 (8.95%)  5/84 (5.95%) 
Eye disorders           
Vision blurred * 1  30/192 (15.63%)  4/192 (2.08%)  4/186 (2.15%)  26/257 (10.12%)  2/84 (2.38%) 
Retinal detachment * 1  15/192 (7.81%)  1/192 (0.52%)  1/186 (0.54%)  19/257 (7.39%)  0/84 (0.00%) 
Cataract * 1  12/192 (6.25%)  2/192 (1.04%)  4/186 (2.15%)  0/257 (0.00%)  0/84 (0.00%) 
Dry eye * 1  11/192 (5.73%)  10/192 (5.21%)  12/186 (6.45%)  0/257 (0.00%)  0/84 (0.00%) 
Macular oedema * 1  11/192 (5.73%)  0/192 (0.00%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Lacrimation increased * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  5/84 (5.95%) 
Gastrointestinal disorders           
Nausea * 1  78/192 (40.63%)  69/192 (35.94%)  63/186 (33.87%)  68/257 (26.46%)  24/84 (28.57%) 
Diarrhoea * 1  69/192 (35.94%)  26/192 (13.54%)  63/186 (33.87%)  73/257 (28.40%)  6/84 (7.14%) 
Vomiting * 1  57/192 (29.69%)  47/192 (24.48%)  27/186 (14.52%)  39/257 (15.18%)  16/84 (19.05%) 
Constipation * 1  42/192 (21.88%)  27/192 (14.06%)  12/186 (6.45%)  43/257 (16.73%)  9/84 (10.71%) 
Abdominal pain * 1  30/192 (15.63%)  11/192 (5.73%)  11/186 (5.91%)  26/257 (10.12%)  5/84 (5.95%) 
Abdominal pain upper * 1  21/192 (10.94%)  16/192 (8.33%)  17/186 (9.14%)  32/257 (12.45%)  4/84 (4.76%) 
Dyspepsia * 1  11/192 (5.73%)  7/192 (3.65%)  8/186 (4.30%)  0/257 (0.00%)  0/84 (0.00%) 
Stomatitis * 1  4/192 (2.08%)  15/192 (7.81%)  11/186 (5.91%)  0/257 (0.00%)  0/84 (0.00%) 
Dysphagia * 1  2/192 (1.04%)  7/192 (3.65%)  10/186 (5.38%)  0/257 (0.00%)  0/84 (0.00%) 
General disorders           
Fatigue * 1  54/192 (28.13%)  48/192 (25.00%)  56/186 (30.11%)  57/257 (22.18%)  25/84 (29.76%) 
Asthenia * 1  35/192 (18.23%)  36/192 (18.75%)  34/186 (18.28%)  38/257 (14.79%)  13/84 (15.48%) 
Pyrexia * 1  31/192 (16.15%)  27/192 (14.06%)  51/186 (27.42%)  43/257 (16.73%)  11/84 (13.10%) 
Oedema peripheral * 1  20/192 (10.42%)  15/192 (7.81%)  20/186 (10.75%)  28/257 (10.89%)  3/84 (3.57%) 
Chills * 1  9/192 (4.69%)  11/192 (5.73%)  10/186 (5.38%)  0/257 (0.00%)  0/84 (0.00%) 
Influenza like illness * 1  9/192 (4.69%)  10/192 (5.21%)  3/186 (1.61%)  0/257 (0.00%)  0/84 (0.00%) 
Xerosis * 1  4/192 (2.08%)  16/192 (8.33%)  8/186 (4.30%)  0/257 (0.00%)  0/84 (0.00%) 
Pain * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  5/257 (1.95%)  7/84 (8.33%) 
Infections and infestations           
Nasopharyngitis * 1  20/192 (10.42%)  11/192 (5.73%)  18/186 (9.68%)  23/257 (8.95%)  5/84 (5.95%) 
Upper respiratory tract infection * 1  14/192 (7.29%)  5/192 (2.60%)  5/186 (2.69%)  0/257 (0.00%)  0/84 (0.00%) 
Influenza * 1  10/192 (5.21%)  6/192 (3.13%)  8/186 (4.30%)  0/257 (0.00%)  0/84 (0.00%) 
Folliculitis * 1  5/192 (2.60%)  8/192 (4.17%)  10/186 (5.38%)  0/257 (0.00%)  0/84 (0.00%) 
Conjunctivitis * 1  4/192 (2.08%)  8/192 (4.17%)  14/186 (7.53%)  0/257 (0.00%)  0/84 (0.00%) 
Urinary tract infection * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  13/257 (5.06%)  3/84 (3.57%) 
Oral candidiasis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  5/257 (1.95%)  5/84 (5.95%) 
Injury, poisoning and procedural complications           
Sunburn * 1  0/192 (0.00%)  1/192 (0.52%)  19/186 (10.22%)  0/257 (0.00%)  0/84 (0.00%) 
Investigations           
Blood creatine phosphokinase increased * 1  44/192 (22.92%)  2/192 (1.04%)  4/186 (2.15%)  51/257 (19.84%)  0/84 (0.00%) 
Gamma-glutamyltransferase increased * 1  29/192 (15.10%)  20/192 (10.42%)  20/186 (10.75%)  36/257 (14.01%)  7/84 (8.33%) 
Alanine aminotransferase increased * 1  21/192 (10.94%)  10/192 (5.21%)  14/186 (7.53%)  29/257 (11.28%)  1/84 (1.19%) 
Aspartate aminotransferase increased * 1  16/192 (8.33%)  8/192 (4.17%)  15/186 (8.06%)  21/257 (8.17%)  1/84 (1.19%) 
Blood alkaline phosphatase increased * 1  16/192 (8.33%)  6/192 (3.13%)  9/186 (4.84%)  0/257 (0.00%)  0/84 (0.00%) 
Blood creatinine increased * 1  11/192 (5.73%)  3/192 (1.56%)  11/186 (5.91%)  0/257 (0.00%)  0/84 (0.00%) 
Ejection fraction decreased * 1  11/192 (5.73%)  4/192 (2.08%)  1/186 (0.54%)  0/257 (0.00%)  0/84 (0.00%) 
Weight decreased * 1  6/192 (3.13%)  29/192 (15.10%)  20/186 (10.75%)  10/257 (3.89%)  8/84 (9.52%) 
Blood bilirubin increased * 1  2/192 (1.04%)  0/192 (0.00%)  14/186 (7.53%)  0/257 (0.00%)  0/84 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite * 1  16/192 (8.33%)  40/192 (20.83%)  36/186 (19.35%)  23/257 (8.95%)  11/84 (13.10%) 
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  49/192 (25.52%)  84/192 (43.75%)  81/186 (43.55%)  57/257 (22.18%)  35/84 (41.67%) 
Myalgia * 1  26/192 (13.54%)  53/192 (27.60%)  34/186 (18.28%)  35/257 (13.62%)  19/84 (22.62%) 
Pain in extremity * 1  20/192 (10.42%)  41/192 (21.35%)  24/186 (12.90%)  27/257 (10.51%)  11/84 (13.10%) 
Back pain * 1  18/192 (9.38%)  26/192 (13.54%)  10/186 (5.38%)  36/257 (14.01%)  7/84 (8.33%) 
Muscle spasms * 1  17/192 (8.85%)  6/192 (3.13%)  4/186 (2.15%)  18/257 (7.00%)  1/84 (1.19%) 
Musculoskeletal pain * 1  11/192 (5.73%)  30/192 (15.63%)  10/186 (5.38%)  9/257 (3.50%)  10/84 (11.90%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Skin papilloma * 1  12/192 (6.25%)  18/192 (9.38%)  31/186 (16.67%)  16/257 (6.23%)  13/84 (15.48%) 
Seborrhoeic keratosis * 1  11/192 (5.73%)  12/192 (6.25%)  10/186 (5.38%)  6/257 (2.33%)  5/84 (5.95%) 
Keratoacanthoma * 1  4/192 (2.08%)  12/192 (6.25%)  21/186 (11.29%)  4/257 (1.56%)  10/84 (11.90%) 
Melanocytic naevus * 1  3/192 (1.56%)  18/192 (9.38%)  7/186 (3.76%)  4/257 (1.56%)  5/84 (5.95%) 
Squamous cell carcinoma * 1  1/192 (0.52%)  3/192 (1.56%)  10/186 (5.38%)  0/257 (0.00%)  0/84 (0.00%) 
Nervous system disorders           
Headache * 1  41/192 (21.35%)  51/192 (26.56%)  35/186 (18.82%)  30/257 (11.67%)  19/84 (22.62%) 
Dizziness * 1  23/192 (11.98%)  9/192 (4.69%)  5/186 (2.69%)  21/257 (8.17%)  1/84 (1.19%) 
Visual field defect * 1  14/192 (7.29%)  2/192 (1.04%)  3/186 (1.61%)  0/257 (0.00%)  0/84 (0.00%) 
Paraesthesia * 1  11/192 (5.73%)  14/192 (7.29%)  10/186 (5.38%)  7/257 (2.72%)  7/84 (8.33%) 
Dysgeusia * 1  10/192 (5.21%)  22/192 (11.46%)  16/186 (8.60%)  9/257 (3.50%)  5/84 (5.95%) 
Facial paralysis * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  0/257 (0.00%)  5/84 (5.95%) 
Psychiatric disorders           
Insomnia * 1  18/192 (9.38%)  35/192 (18.23%)  15/186 (8.06%)  17/257 (6.61%)  12/84 (14.29%) 
Anxiety * 1  12/192 (6.25%)  7/192 (3.65%)  4/186 (2.15%)  5/257 (1.95%)  7/84 (8.33%) 
Respiratory, thoracic and mediastinal disorders           
Cough * 1  15/192 (7.81%)  17/192 (8.85%)  12/186 (6.45%)  15/257 (5.84%)  4/84 (4.76%) 
Dyspnoea * 1  13/192 (6.77%)  8/192 (4.17%)  14/186 (7.53%)  10/257 (3.89%)  5/84 (5.95%) 
Oropharyngeal pain * 1  4/192 (2.08%)  9/192 (4.69%)  12/186 (6.45%)  0/257 (0.00%)  0/84 (0.00%) 
Skin and subcutaneous tissue disorders           
Dry skin * 1  27/192 (14.06%)  58/192 (30.21%)  42/186 (22.58%)  21/257 (8.17%)  19/84 (22.62%) 
Hyperkeratosis * 1  27/192 (14.06%)  72/192 (37.50%)  54/186 (29.03%)  25/257 (9.73%)  35/84 (41.67%) 
Rash * 1  27/192 (14.06%)  41/192 (21.35%)  54/186 (29.03%)  18/257 (7.00%)  23/84 (27.38%) 
Alopecia * 1  26/192 (13.54%)  107/192 (55.73%)  68/186 (36.56%)  33/257 (12.84%)  28/84 (33.33%) 
Pruritus * 1  21/192 (10.94%)  42/192 (21.88%)  20/186 (10.75%)  19/257 (7.39%)  10/84 (11.90%) 
Palmoplantar keratoderma * 1  17/192 (8.85%)  49/192 (25.52%)  29/186 (15.59%)  17/257 (6.61%)  16/84 (19.05%) 
Erythema * 1  13/192 (6.77%)  24/192 (12.50%)  31/186 (16.67%)  14/257 (5.45%)  11/84 (13.10%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  13/192 (6.77%)  98/192 (51.04%)  26/186 (13.98%)  10/257 (3.89%)  31/84 (36.90%) 
Keratosis pilaris * 1  9/192 (4.69%)  33/192 (17.19%)  43/186 (23.12%)  5/257 (1.95%)  10/84 (11.90%) 
Photosensitivity reaction * 1  8/192 (4.17%)  7/192 (3.65%)  45/186 (24.19%)  0/257 (0.00%)  0/84 (0.00%) 
Actinic keratosis * 1  5/192 (2.60%)  4/192 (2.08%)  10/186 (5.38%)  0/257 (0.00%)  0/84 (0.00%) 
Pruritus generalised * 1  4/192 (2.08%)  18/192 (9.38%)  19/186 (10.22%)  6/257 (2.33%)  9/84 (10.71%) 
Rash generalised * 1  4/192 (2.08%)  12/192 (6.25%)  16/186 (8.60%)  0/257 (0.00%)  0/84 (0.00%) 
Rash maculo-papular * 1  3/192 (1.56%)  18/192 (9.38%)  27/186 (14.52%)  0/257 (0.00%)  0/84 (0.00%) 
Skin hyperpigmentation * 1  3/192 (1.56%)  15/192 (7.81%)  3/186 (1.61%)  0/257 (0.00%)  0/84 (0.00%) 
Rash papular * 1  2/192 (1.04%)  10/192 (5.21%)  6/186 (3.23%)  0/257 (0.00%)  0/84 (0.00%) 
Skin lesion * 1  2/192 (1.04%)  9/192 (4.69%)  12/186 (6.45%)  0/257 (0.00%)  0/84 (0.00%) 
Skin exfoliation * 1  1/192 (0.52%)  11/192 (5.73%)  4/186 (2.15%)  0/257 (0.00%)  0/84 (0.00%) 
Solar dermatitis * 1  1/192 (0.52%)  1/192 (0.52%)  15/186 (8.06%)  0/257 (0.00%)  0/84 (0.00%) 
Vitiligo * 1  0/192 (0.00%)  0/192 (0.00%)  0/186 (0.00%)  9/257 (3.50%)  5/84 (5.95%) 
Vascular disorders           
Hypertension * 1  21/192 (10.94%)  11/192 (5.73%)  21/186 (11.29%)  20/257 (7.78%)  4/84 (4.76%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 19.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01909453    
Other Study ID Numbers: CMEK162B2301
C4221004 ( Other Identifier: Alias Study Number )
2013-001176-38 ( EudraCT Number )
First Submitted: July 24, 2013
First Posted: July 26, 2013
Results First Submitted: May 5, 2021
Results First Posted: July 12, 2021
Last Update Posted: April 26, 2024