A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT01871805
• Recruitment Status: Completed
• First Posted: June 7, 2013
• Results First Posted: February 12, 2016
• Last Update Posted: August 21, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Intervention: Drug: Alectinib
• Enrollment: 134

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40/150 mg)	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received single dose of 20 or 40 milligrams (mg) alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg twice daily (BID) dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received 150 mg alectinib capsules orally to make a dose of 600 mg BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Period Title: Phase I
Started	7	7	13	7	13	0
Completed	0	0	0	0	0	0
Not Completed	7	7	13	7	13	0
Reason Not Completed
Death	7	4	6	2	9	0
Alive in Survival Follow-up	0	2	4	5	4	0
Lost to Follow-up	0	1	3	0	0	0
Period Title: Phase II
Started	0	0	0	0	0	87
Completed	0	0	0	0	0	0
Not Completed	0	0	0	0	0	87
Reason Not Completed
Death	0	0	0	0	0	45
Alive in Survival Follow-up	0	0	0	0	0	29
Lost to Follow-up	0	0	0	0	0	13

Baseline Characteristics

Arm/Group Title		Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40/150 mg)	Alectinib 600 mg (Fed): Phase II	Total
Arm/Group Description		Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Total of all reporting groups
Overall Number of Baseline Participants		7	7	13	7	13	87	134
Baseline Analysis Population Description		Safety population included all participants who received any dose of alectinib.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	13 participants	7 participants	13 participants	87 participants	134 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	7 100.0%	6 85.7%	12 92.3%	7 100.0%	10 76.9%	71 81.6%	113 84.3%
	>=65 years	0 0.0%	1 14.3%	1 7.7%	0 0.0%	3 23.1%	16 18.4%	21 15.7%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	13 participants	7 participants	13 participants	87 participants	134 participants
	Female	2 28.6%	4 57.1%	3 23.1%	2 28.6%	9 69.2%	48 55.2%	68 50.7%
	Male	5 71.4%	3 42.9%	10 76.9%	5 71.4%	4 30.8%	39 44.8%	66 49.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs): Phase I
Description	The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of >=7 days which the Investigator could not rule out as been related to alectinib.
Time Frame	Throughout Cycle 1 of Phase I (21 days)

Outcome Measure Data

Analysis Population Description

Phase I safety population

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40/150 mg)
Arm/Group Description:	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	7	7	13	7	13
Measure Type: Number; Unit of Measure: participants
	0	0	0	0	2

2. Primary Outcome

Title	Recommended Phase II Dose (RP2D): Phase I
Description	RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.
Time Frame	Throughout Cycle 1 of Phase I (21 days)

Outcome Measure Data

Analysis Population Description

Phase I safety population

Arm/Group Title	Alectinib: Phase I
Arm/Group Description:	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 240, 300, 460, 600, 760, or 900 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	47
Measure Type: Number; Unit of Measure: mg
	600

3. Primary Outcome

Title	Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II
Description	Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).
Time Frame	Cycle 1 Day 1 up to 194 weeks (assessed at every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II Response evaluable (RE) population comprised all Phase II participants with measurable disease at baseline who had a baseline tumor assessment and received at least one dose of alectinib.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	67
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	52.2; (39.67 to 64.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib 600 mg (Fed): Phase II
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0056
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I
Description	Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I RE population comprised all Phase I participants with measurable disease at baseline who had a baseline tumor assessment and received at least one dose of alectinib.

Arm/Group Title	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib Other Than 600 mg (Fasted/Fed): Phase I
Arm/Group Description:	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 240, 300, 460, 760, or 900 mg on Cycle 1 Day -3 and then received 300, 460, 760, or 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	13	34
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	69.2; (38.57 to 90.91)	55.9; (37.89 to 72.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0251
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib Other Than 600 mg (Fasted/Fed): Phase I
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0203
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments	[Not Specified]

5. Secondary Outcome

Title	Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I
Description	DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I RE population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib Other Than 600 mg (Fasted/Fed): Phase I
Arm/Group Description:	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 240, 300, 460, 760, or 900 mg on Cycle 1 Day -3 and then received 300, 460, 760, or 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	9	19
Median (95% Confidence Interval); Unit of Measure: months
	12.2; (4.9 to 20.9)	11.0; (6.3 to 14.8)

6. Secondary Outcome

Title	Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II
Description	Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	52.9; (41.87 to 63.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib 600 mg (Fed): Phase II
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0010
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments	[Not Specified]

7. Secondary Outcome

Title	Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II
Description	Disease control rate assessed according to RECIST v1.1 was defined as the percentage of participants with a best overall response of CR, PR, or stable disease (SD) lasting for at least 12 weeks, after the first dose of alectinib. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. 95% CI for rate was constructed using Clopper-Pearson method.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	66.7; (55.75 to 76.42)

8. Secondary Outcome

Title	Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II
Description	Percentage of participants with disease progression according to RECIST v1.1 by IRC is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Measure Type: Number; Unit of Measure: percentage of participants
	66.7

9. Secondary Outcome

Title	Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II
Description	PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Median (95% Confidence Interval); Unit of Measure: months
	8.2; (6.3 to 12.6)

10. Secondary Outcome

Title	Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II
Description	Percentage of participants with disease progression according to RECIST v1.1 by investigator is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Measure Type: Number; Unit of Measure: percentage of participants
	70.1

11. Secondary Outcome

Title	PFS According to RECIST v1.1 by Investigator: Phase II
Description	PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Median (95% Confidence Interval); Unit of Measure: months
	8.4; (5.5 to 12.7)

12. Secondary Outcome

Title	Percentage of Participants Who Died Due to Any Cause: Phase II
Description	[Not Specified]
Time Frame	Baseline up to death (any cause) (maximum follow up 284 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Measure Type: Number; Unit of Measure: percentage of participants
	51.7

13. Secondary Outcome

Title	Overall Survival (OS) Time: Phase II
Description	OS was defined as the time between date of first dose and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants without any follow-up information were censored at the date of first dose. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Baseline up to death (any cause) (maximum follow up 284 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	87
Median (95% Confidence Interval); Unit of Measure: months
	27.9 [1]; (17.2 to NA)

[1]

Upper limit of 95% CI was not estimable due to low number of events and longer observation time.

14. Secondary Outcome

Title	DOR According to RECIST v1.1 by IRC: Phase II
Description	DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	35
Median (95% Confidence Interval); Unit of Measure: months
	14.9 [1]; (6.9 to NA)

[1]

Upper limit of 95% CI was not estimable due to low number of events and longer observation time.

15. Secondary Outcome

Title	DOR According to RECIST v1.1 by Investigator: Phase II
Description	DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	46
Median (95% Confidence Interval); Unit of Measure: months
	13.3; (8.8 to 18.2)

16. Secondary Outcome

Title	Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II
Description	COR rate (CORR) was defined as the percentage of participants who had a CR or PR of the baseline central nervous system (CNS) lesions, based on RECIST v.1.1. CNS responses according to RECIST v1.1 did not have to be confirmed. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). 95% CI was computed using the Clopper-Pearson method.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants with measurable CNS lesions at baseline based on RECIST v1.1 according to IRC.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	16
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	75.0; (47.62 to 92.73)

17. Secondary Outcome

Title	Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II
Description	CORR was defined as the percentage of participants who had a CR or PR according to RANO criteria of the baseline CNS lesions. As per RANO criteria, CR was defined as disappearance of all enhancing measurable and non-measurable disease, and no new lesions along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and stable or improved non enhancing T2/FLAIR lesions; PR was defined as 50% or more decrease in sum of the products of the diameters (SPD) of measurable enhancing measurable lesions, no new lesion along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and no progression of non-measurable disease (enhancing and non-enhancing T2/FLAIR lesions. Clopper-Pearson method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants with measurable CNS lesions at baseline according to RANO criteria by IRC.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	11
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	54.5; (23.38 to 83.25)

18. Secondary Outcome

Title	CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II
Description	CDOR was defined for CNS responders as the time from the first observation of a CNS response of CR or PR until first observation of CNS progression or death from any cause. An analysis by IRC using RECIST v1.1 was performed. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	12
Median (95% Confidence Interval); Unit of Measure: months
	11.1 [1]; (5.8 to NA)

[1]

Upper limit of 95% CI was not estimable due to low number of events and longer observation time.

19. Secondary Outcome

Title	CDOR According to RANO Criteria by IRC: Phase II
Description	CDOR was defined as the time from the first observation of a CNS response of CR or PR according to RANO criteria until first observation of CNS progression or death from any cause. An analysis by RANO criteria was performed. Definitions of CR or PR as per RANO was included in description of Outcome Measure 17. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease) and clear worsening of neurological status with respect to the previous timepoint. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	6
Median (95% Confidence Interval); Unit of Measure: months
	12.1 [1]; (11.1 to NA)

[1]

Upper limit of 95% CI was not estimable due to low number of events and longer observation time.

20. Secondary Outcome

Title	Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II
Description	CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RECIST v1.1. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	16
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0.00 to 20.59)

21. Secondary Outcome

Title	Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II
Description	CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RANO criteria. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Data were not estimable due to low number of responders and longer observation time.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description:	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

22. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I
Description	[Not Specified]
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I pharmacokinetic (PK) evaluable population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 240 mg Once and 300 mg BID (Fasted): Phase I	Alectinib 240 mg Once and 300 mg BID (Fed): Phase I	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description:	Participants (in fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants (in non-fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	3	1	3	7	6	6	7	7	6
Mean (Standard Deviation); Unit of Measure: nanograms per milliliter (ng/mL)
	73.5 (12.4)	87.7	45.3 (9.24)	142.00 (71.4)	158.0 (67.2)	186.0 (43.1)	257.0 (83.1)	186.0 (120.0)	295.0 (131.0)

23. Secondary Outcome

Title	Cmax After Multiple Dose of Alectinib: Phase I
Description	[Not Specified]
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description:	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	6	7	5	6	5	7	4
Mean (Standard Deviation); Unit of Measure: ng/mL
	259 (79.0)	618 (165)	765 (176)	670 (360)	733 (98.0)	1140 (448)	1200 (311)

24. Secondary Outcome

Title	Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I
Description	AUCinf = AUC from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0- t) plus AUC (t-inf).
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 240 mg Once and 300 mg BID (Fasted): Phase I	Alectinib 240 mg Once and 300 mg BID (Fed): Phase I	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description:	Participants (in fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants (in non-fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	3	1	3	7	6	6	7	7	6
Mean (Standard Deviation); Unit of Measure: hour*ng/mL
	1360 (436)	858	1030 (481)	3280 (2240)	3310 (1110)	3190 (1510)	4090 (1680)	3730 (2310)	7790 (6210)

25. Secondary Outcome

Title	AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I
Description	[Not Specified]
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description:	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed	6	7	5	6	5	7	4
Mean (Standard Deviation); Unit of Measure: hour*ng/mL
	1800 (562)	4510 (1700)	5970 (1140)	5300 (3180)	5780 (1020)	9800 (4660)	9500 (2670)

26. Secondary Outcome

Title	Ctrough After Multiple Dose of Alectinib: Phase II
Description	[Not Specified]
Time Frame	Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specified timepoint.

Arm/Group Title		Alectinib 600 mg (Fed): Phase II
Arm/Group Description:		Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed		61
Mean (Standard Deviation); Unit of Measure: ng/mL
Cycle 2 Day 1	Number Analyzed	61 participants
		473 (277)
Cycle 3 Day 1	Number Analyzed	51 participants
		521 (272)
Cycle 4 Day 1	Number Analyzed	52 participants
		538 (279)
Cycle 5 Day 1	Number Analyzed	45 participants
		538 (226)

27. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II
Description	EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to lie between 0-100 scale; for each of the symptom scales, higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below (e.g. Global health status/QoL [quality of life]) represents absolute data at baseline. QoL=quality of life
Time Frame	Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specified timepoint.

Arm/Group Title		Alectinib 600 mg (Fed): Phase II
Arm/Group Description:		Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed		79
Mean (Standard Deviation); Unit of Measure: units on a scale
Global health status/QoL: Baseline	Number Analyzed	79 participants
		53.59 (24.27)
Global health status/QoL: Week 6	Number Analyzed	64 participants
		15.89 (25.66)
Global health status/QoL: Week 9	Number Analyzed	1 participants
		0.00
Global health status/QoL: Week 12	Number Analyzed	54 participants
		18.83 (23.41)
Global health status/QoL: Week 15	Number Analyzed	1 participants
		0.00
Global health status/QoL: Week 18	Number Analyzed	49 participants
		15.65 (23.73)
Global health status/QoL: Week 21	Number Analyzed	1 participants
		0.00
Global health status/QoL: Week 24	Number Analyzed	41 participants
		15.65 (20.77)
Global health status/QoL: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Global health status/QoL: Week 30	Number Analyzed	39 participants
		13.03 (19.57)
Global health status/QoL: Week 33	Number Analyzed	3 participants
		-5.56 (9.62)
Global health status/QoL: Week 36	Number Analyzed	38 participants
		12.28 (20.57)
Global health status/QoL: Week 39	Number Analyzed	2 participants
		4.17 (5.89)
Global health status/QoL: Week 42	Number Analyzed	36 participants
		10.19 (19.33)
Global health status/QoL: Week 45	Number Analyzed	4 participants
		-10.42 (12.50)
Global health status/QoL: Week 48	Number Analyzed	33 participants
		11.11 (19.06)
Global health status/QoL: Week 51	Number Analyzed	2 participants
		12.50 (17.68)
Global health status/QoL: Week 54	Number Analyzed	31 participants
		9.95 (16.86)
Global health status/QoL: Week 57	Number Analyzed	5 participants
		-3.33 (21.73)
Global health status/QoL: Week 60	Number Analyzed	30 participants
		10.28 (19.54)
Global health status/QoL: Week 63	Number Analyzed	3 participants
		11.11 (19.25)
Global health status/QoL: Week 66	Number Analyzed	26 participants
		15.06 (17.80)
Global health status/QoL: Week 69	Number Analyzed	4 participants
		12.50 (15.96)
Global health status/QoL: Week 72	Number Analyzed	23 participants
		8.33 (18.12)
Global health status/QoL: Week 75	Number Analyzed	2 participants
		16.67 (23.57)
Global health status/QoL: Week 78	Number Analyzed	21 participants
		10.32 (16.44)
Global health status/QoL: Week 81	Number Analyzed	2 participants
		16.67 (23.57)
Global health status/QoL: Week 84	Number Analyzed	13 participants
		10.90 (14.98)
Global health status/QoL: Week 87	Number Analyzed	3 participants
		11.11 (19.25)
Global health status/QoL: Week 90	Number Analyzed	8 participants
		4.17 (11.79)
Global health status/QoL: Week 93	Number Analyzed	2 participants
		-29.17 (41.25)
Global health status/QoL: Week 96	Number Analyzed	3 participants
		0.00 (22.05)
Global health status/QoL: Week 99	Number Analyzed	1 participants
		-16.67
Global health status/QoL: Week 105	Number Analyzed	1 participants
		-16.67
Global health status/QoL: Week 111	Number Analyzed	1 participants
		0.00
Global health status/QoL: Week 117	Number Analyzed	1 participants
		0.00
Global health status/QoL: Last visit	Number Analyzed	73 participants
		7.99 (21.27)
Physical functioning: Baseline	Number Analyzed	79 participants
		69.96 (24.43)
Physical functioning: Week 6	Number Analyzed	64 participants
		4.69 (17.44)
Physical functioning: Week 9	Number Analyzed	1 participants
		0.00
Physical functioning: Week 12	Number Analyzed	54 participants
		4.20 (22.37)
Physical functioning: Week 15	Number Analyzed	1 participants
		0.00
Physical functioning: Week 18	Number Analyzed	51 participants
		7.58 (18.23)
Physical functioning: Week 21	Number Analyzed	1 participants
		0.00
Physical functioning: Week 24	Number Analyzed	42 participants
		4.13 (16.33)
Physical functioning: Week 27	Number Analyzed	2 participants
		3.33 (4.71)
Physical functioning: Week 30	Number Analyzed	39 participants
		2.22 (17.39)
Physical functioning: Week 33	Number Analyzed	3 participants
		0.00 (13.33)
Physical functioning: Week 36	Number Analyzed	38 participants
		4.21 (18.10)
Physical functioning: Week 39	Number Analyzed	2 participants
		3.33 (14.14)
Physical functioning: Week 42	Number Analyzed	36 participants
		6.85 (18.89)
Physical functioning: Week 45	Number Analyzed	4 participants
		-3.33 (22.11)
Physical functioning: Week 48	Number Analyzed	33 participants
		5.25 (16.81)
Physical functioning: Week 51	Number Analyzed	2 participants
		0.00 (18.86)
Physical functioning: Week 54	Number Analyzed	32 participants
		6.67 (18.32)
Physical functioning: Week 57	Number Analyzed	5 participants
		0.00 (20.55)
Physical functioning: Week 60	Number Analyzed	30 participants
		7.56 (22.67)
Physical functioning: Week 63	Number Analyzed	3 participants
		-6.67 (11.55)
Physical functioning: Week 66	Number Analyzed	26 participants
		8.97 (19.13)
Physical functioning: Week 69	Number Analyzed	4 participants
		8.33 (16.67)
Physical functioning: Week 72	Number Analyzed	23 participants
		4.20 (22.70)
Physical functioning: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Physical functioning: Week 78	Number Analyzed	21 participants
		6.98 (19.83)
Physical functioning: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Physical functioning: Week 84	Number Analyzed	13 participants
		3.08 (21.71)
Physical functioning: Week 87	Number Analyzed	3 participants
		-6.67 (11.55)
Physical functioning: Week 90	Number Analyzed	8 participants
		7.50 (18.32)
Physical functioning: Week 93	Number Analyzed	2 participants
		-26.67 (28.28)
Physical functioning: Week 96	Number Analyzed	3 participants
		33.33 (11.55)
Physical functioning: Week 99	Number Analyzed	1 participants
		-6.67
Physical functioning: Week 105	Number Analyzed	1 participants
		0.00
Physical functioning: Week 111	Number Analyzed	1 participants
		0.00
Physical functioning: Week 117	Number Analyzed	1 participants
		0.00
Physical functioning: Last visit	Number Analyzed	73 participants
		2.28 (21.64)
Role functioning: Baseline	Number Analyzed	79 participants
		58.86 (34.06)
Role functioning: Week 6	Number Analyzed	64 participants
		14.84 (32.00)
Role functioning: Week 9	Number Analyzed	1 participants
		0.00
Role functioning: Week 12	Number Analyzed	54 participants
		12.65 (32.69)
Role functioning: Week 15	Number Analyzed	1 participants
		0.00
Role functioning: Week 18	Number Analyzed	51 participants
		12.42 (31.94)
Role functioning: Week 21	Number Analyzed	1 participants
		0.00
Role functioning: Week 24	Number Analyzed	42 participants
		8.73 (27.85)
Role functioning: Week 27	Number Analyzed	2 participants
		-8.33 (11.79)
Role functioning: Week 30	Number Analyzed	39 participants
		9.83 (24.70)
Role functioning: Week 33	Number Analyzed	3 participants
		-33.33 (33.33)
Role functioning: Week 36	Number Analyzed	38 participants
		9.65 (24.70)
Role functioning: Week 39	Number Analyzed	2 participants
		-33.33 (0.00)
Role functioning: Week 42	Number Analyzed	36 participants
		6.48 (28.81)
Role functioning Week 45	Number Analyzed	4 participants
		-20.83 (15.96)
Role functioning: Week 48	Number Analyzed	32 participants
		10.94 (24.54)
Role functioning: Week 51	Number Analyzed	2 participants
		-16.67 (23.57)
Role functioning: Week 54	Number Analyzed	32 participants
		7.29 (24.30)
Role functioning: Week 57	Number Analyzed	5 participants
		-13.33 (18.26)
Role functioning: Week 60	Number Analyzed	30 participants
		8.89 (27.24)
Role functioning: Week 63	Number Analyzed	3 participants
		-5.56 (9.62)
Role functioning: Week 66	Number Analyzed	26 participants
		8.97 (29.90)
Role functioning: Week 69	Number Analyzed	4 participants
		-16.67 (33.33)
Role functioning: Week 72	Number Analyzed	23 participants
		7.97 (27.46)
Role functioning: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Role functioning: Week 78	Number Analyzed	21 participants
		9.52 (28.66)
Role functioning: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Role functioning: Week 84	Number Analyzed	13 participants
		5.13 (31.46)
Role functioning: Week 87	Number Analyzed	3 participants
		-11.11 (19.25)
Role functioning: Week 90	Number Analyzed	8 participants
		-4.17 (19.42)
Role functioning: Week 93	Number Analyzed	2 participants
		-41.67 (35.36)
Role functioning: Week 96	Number Analyzed	3 participants
		11.11 (19.25)
Role functioning: Week 99	Number Analyzed	1 participants
		-16.67
Role functioning: Week 105	Number Analyzed	1 participants
		0.00
Role functioning: Week 111	Number Analyzed	1 participants
		0.00
Role functioning: Week 117	Number Analyzed	1 participants
		0.00
Role functioning: Last visit	Number Analyzed	73 participants
		9.36 (34.47)
Emotional functioning: Baseline	Number Analyzed	79 participants
		73.49 (21.40)
Emotional functioning: Week 6	Number Analyzed	64 participants
		7.99 (18.75)
Emotional functioning: Week 9	Number Analyzed	1 participants
		0.00
Emotional functioning: Week 12	Number Analyzed	54 participants
		11.01 (17.04)
Emotional functioning: Week 15	Number Analyzed	1 participants
		0.00
Emotional functioning: Week 18	Number Analyzed	49 participants
		13.44 (21.17)
Emotional functioning: Week 21	Number Analyzed	1 participants
		0.00
Emotional functioning: Week 24	Number Analyzed	41 participants
		10.37 (16.75)
Emotional functioning: Week 27	Number Analyzed	2 participants
		-4.17 (5.89)
Emotional functioning: Week 30	Number Analyzed	39 participants
		9.40 (20.34)
Emotional functioning: Week 33	Number Analyzed	3 participants
		-30.56 (26.79)
Emotional functioning: Week 36	Number Analyzed	38 participants
		7.89 (19.85)
Emotional functioning: Week 39	Number Analyzed	2 participants
		-4.17 (5.89)
Emotional functioning: Week 42	Number Analyzed	36 participants
		7.41 (18.12)
Emotional functioning Week 45	Number Analyzed	4 participants
		-6.25 (7.98)
Emotional functioning: Week 48	Number Analyzed	33 participants
		6.73 (15.23)
Emotional functioning: Week 51	Number Analyzed	2 participants
		0.00 (0.00)
Emotional functioning: Week 54	Number Analyzed	31 participants
		3.49 (13.40)
Emotional functioning: Week 57	Number Analyzed	5 participants
		-6.67 (18.07)
Emotional functioning: Week 60	Number Analyzed	30 participants
		3.33 (14.12)
Emotional functioning: Week 63	Number Analyzed	3 participants
		-11.11 (34.69)
Emotional functioning: Week 66	Number Analyzed	26 participants
		5.45 (14.52)
Emotional functioning: Week 69	Number Analyzed	4 participants
		-8.33 (26.35)
Emotional functioning: Week 72	Number Analyzed	23 participants
		5.07 (21.43)
Emotional functioning: Week 75	Number Analyzed	2 participants
		8.33 (11.79)
Emotional functioning: Week 78	Number Analyzed	21 participants
		-1.19 (19.77)
Emotional functioning: Week 81	Number Analyzed	2 participants
		4.17 (5.89)
Emotional functioning: Week 84	Number Analyzed	13 participants
		1.28 (19.79)
Emotional functioning: Week 87	Number Analyzed	3 participants
		-11.11 (34.69)
Emotional functioning: Week 90	Number Analyzed	8 participants
		1.04 (8.26)
Emotional functioning: Week 93	Number Analyzed	2 participants
		-12.50 (17.68)
Emotional functioning: Week 96	Number Analyzed	3 participants
		11.11 (19.25)
Emotional functioning: Week 99	Number Analyzed	1 participants
		0.00
Emotional functioning: Week 105	Number Analyzed	1 participants
		0.00
Emotional functioning: Week 111	Number Analyzed	1 participants
		0.00
Emotional functioning: Week 117	Number Analyzed	1 participants
		0.00
Emotional functioning: Last visit	Number Analyzed	73 participants
		4.76 (19.86)
Cognitive functioning: Baseline	Number Analyzed	79 participants
		77.85 (24.13)
Cognitive functioning: Week 6	Number Analyzed	64 participants
		2.34 (20.76)
Cognitive functioning: Week 9	Number Analyzed	1 participants
		0.00
Cognitive functioning: Week 12	Number Analyzed	54 participants
		2.78 (15.44)
Cognitive functioning: Week 15	Number Analyzed	1 participants
		0.00
Cognitive functioning: Week 18	Number Analyzed	49 participants
		2.04 (15.82)
Cognitive functioning: Week 21	Number Analyzed	1 participants
		0.00
Cognitive functioning: Week 24	Number Analyzed	41 participants
		-3.25 (16.34)
Cognitive functioning: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Cognitive functioning: Week 30	Number Analyzed	39 participants
		-1.28 (17.68)
Cognitive functioning: Week 33	Number Analyzed	3 participants
		-27.78 (25.46)
Cognitive functioning: Week 36	Number Analyzed	38 participants
		-2.63 (13.16)
Cognitive functioning: Week 39	Number Analyzed	2 participants
		-25.00 (35.36)
Cognitive functioning: Week 42	Number Analyzed	36 participants
		-0.46 (14.08)
Cognitive functioning Week 45	Number Analyzed	4 participants
		-4.17 (51.59)
Cognitive functioning: Week 48	Number Analyzed	33 participants
		-6.06 (21.58)
Cognitive functioning: Week 51	Number Analyzed	2 participants
		-33.33 (0.00)
Cognitive functioning: Week 54	Number Analyzed	31 participants
		-7.53 (22.29)
Cognitive functioning: Week 57	Number Analyzed	5 participants
		0.00 (31.18)
Cognitive functioning: Week 60	Number Analyzed	30 participants
		-6.11 (21.66)
Cognitive functioning: Week 63	Number Analyzed	3 participants
		11.11 (19.25)
Cognitive functioning: Week 66	Number Analyzed	26 participants
		-8.97 (22.23)
Cognitive functioning: Week 69	Number Analyzed	4 participants
		4.17 (8.33)
Cognitive functioning: Week 72	Number Analyzed	23 participants
		-7.97 (20.64)
Cognitive functioning: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Cognitive functioning: Week 78	Number Analyzed	21 participants
		-9.52 (25.59)
Cognitive functioning: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Cognitive functioning: Week 84	Number Analyzed	13 participants
		-3.85 (20.59)
Cognitive functioning: Week 87	Number Analyzed	3 participants
		-11.11 (19.25)
Cognitive functioning: Week 90	Number Analyzed	8 participants
		-8.33 (15.43)
Cognitive functioning: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Cognitive functioning: Week 96	Number Analyzed	3 participants
		-22.22 (19.25)
Cognitive functioning: Week 99	Number Analyzed	1 participants
		0.00
Cognitive functioning: Week 105	Number Analyzed	1 participants
		0.00
Cognitive functioning: Week 111	Number Analyzed	1 participants
		0.00
Cognitive functioning: Week 117	Number Analyzed	1 participants
		0.00
Cognitive functioning: Last visit	Number Analyzed	73 participants
		-4.79 (24.45)
Social functioning: Baseline	Number Analyzed	79 participants
		60.55 (35.32)
Social functioning: Week 6	Number Analyzed	64 participants
		11.20 (23.20)
Social functioning: Week 9	Number Analyzed	1 participants
		0.00
Social functioning: Week 12	Number Analyzed	54 participants
		10.19 (27.93)
Social functioning: Week 15	Number Analyzed	1 participants
		0.00
Social functioning: Week 18	Number Analyzed	49 participants
		13.27 (25.45)
Social functioning: Week 21	Number Analyzed	1 participants
		0.00
Social functioning: Week 24	Number Analyzed	41 participants
		8.54 (26.38)
Social functioning: Week 27	Number Analyzed	2 participants
		16.67 (23.57)
Social functioning: Week 30	Number Analyzed	39 participants
		14.53 (31.11)
Social functioning: Week 33	Number Analyzed	3 participants
		5.56 (25.46)
Social functioning: Week 36	Number Analyzed	38 participants
		9.21 (32.35)
Social functioning: Week 39	Number Analyzed	2 participants
		-8.33 (11.79)
Social functioning: Week 42	Number Analyzed	36 participants
		8.80 (30.47)
Social functioning: Week 45	Number Analyzed	4 participants
		4.17 (20.97)
Social functioning: Week 48	Number Analyzed	33 participants
		16.16 (29.31)
Social functioning: Week 51	Number Analyzed	2 participants
		-8.33 (11.79)
Social functioning: Week 54	Number Analyzed	31 participants
		12.37 (28.53)
Social functioning: Week 57	Number Analyzed	5 participants
		3.33 (18.26)
Social functioning: Week 60	Number Analyzed	30 participants
		8.33 (25.43)
Social functioning: Week 63	Number Analyzed	3 participants
		0.00 (33.33)
Social functioning: Week 66	Number Analyzed	26 participants
		5.77 (31.95)
Social functioning: Week 69	Number Analyzed	4 participants
		20.83 (25.00)
Social functioning: Week 72	Number Analyzed	23 participants
		11.59 (23.80)
Social functioning: Week 75	Number Analyzed	2 participants
		16.67 (23.57)
Social functioning: Week 78	Number Analyzed	21 participants
		12.70 (23.51)
Social functioning: Week 81	Number Analyzed	2 participants
		16.67 (23.57)
Social functioning: Week 84	Number Analyzed	13 participants
		8.97 (29.36)
Social functioning: Week 87	Number Analyzed	3 participants
		27.78 (25.46)
Social functioning: Week 90	Number Analyzed	8 participants
		14.58 (16.52)
Social functioning: Week 93	Number Analyzed	2 participants
		-8.33 (82.50)
Social functioning: Week 96	Number Analyzed	3 participants
		16.67 (16.67)
Social functioning: Week 99	Number Analyzed	1 participants
		0.00
Social functioning: Week 105	Number Analyzed	1 participants
		0.00
Social functioning: Week 111	Number Analyzed	1 participants
		0.00
Social functioning: Week 117	Number Analyzed	1 participants
		0.00
Social functioning: Last visit	Number Analyzed	73 participants
		3.20 (30.39)
Fatigue: Baseline	Number Analyzed	79 participants
		45.57 (27.02)
Fatigue: Week 6	Number Analyzed	64 participants
		-10.94 (25.70)
Fatigue: Week 9	Number Analyzed	1 participants
		-11.11
Fatigue: Week 12	Number Analyzed	54 participants
		-11.11 (27.73)
Fatigue: Week 15	Number Analyzed	1 participants
		0.00
Fatigue: Week 18	Number Analyzed	51 participants
		-12.85 (24.88)
Fatigue: Week 21	Number Analyzed	1 participants
		0.00
Fatigue: Week 24	Number Analyzed	42 participants
		-10.05 (22.06)
Fatigue: Week 27	Number Analyzed	2 participants
		5.56 (7.86)
Fatigue: Week 30	Number Analyzed	39 participants
		-9.97 (23.47)
Fatigue: Week 33	Number Analyzed	3 participants
		14.81 (6.42)
Fatigue: Week 36	Number Analyzed	38 participants
		-10.23 (25.75)
Fatigue: Week 39	Number Analyzed	2 participants
		5.56 (7.86)
Fatigue: Week 42	Number Analyzed	36 participants
		-9.26 (21.50)
Fatigue: Week 45	Number Analyzed	4 participants
		0.00 (24.00)
Fatigue: Week 48	Number Analyzed	32 participants
		-11.11 (22.93)
Fatigue: Week 51	Number Analyzed	2 participants
		0.00 (47.14)
Fatigue: Week 54	Number Analyzed	32 participants
		-7.64 (18.39)
Fatigue: Week 57	Number Analyzed	5 participants
		4.44 (16.85)
Fatigue: Week 60	Number Analyzed	30 participants
		-7.78 (21.27)
Fatigue: Week 63	Number Analyzed	3 participants
		7.41 (23.13)
Fatigue: Week 66	Number Analyzed	26 participants
		-7.69 (20.07)
Fatigue: Week 69	Number Analyzed	4 participants
		-8.33 (10.64)
Fatigue: Week 72	Number Analyzed	23 participants
		-8.21 (22.28)
Fatigue: Week 75	Number Analyzed	2 participants
		-5.56 (7.86)
Fatigue: Week 78	Number Analyzed	21 participants
		-6.35 (23.19)
Fatigue: Week 81	Number Analyzed	2 participants
		-5.56 (7.86)
Fatigue: Week 84	Number Analyzed	13 participants
		-9.40 (18.62)
Fatigue: Week 87	Number Analyzed	3 participants
		0.00 (11.11)
Fatigue: Week 90	Number Analyzed	8 participants
		-8.33 (17.57)
Fatigue: Week 93	Number Analyzed	2 participants
		33.33 (31.43)
Fatigue: Week 96	Number Analyzed	3 participants
		-18.52 (6.42)
Fatigue: Week 99	Number Analyzed	1 participants
		0.00
Fatigue: Week 105	Number Analyzed	1 participants
		0.00
Fatigue: Week 111	Number Analyzed	1 participants
		0.00
Fatigue: Week 117	Number Analyzed	1 participants
		0.00
Fatigue: Last visit	Number Analyzed	73 participants
		-6.85 (21.65)
Nausea and vomiting: Baseline	Number Analyzed	79 participants
		15.61 (20.73)
Nausea and vomiting: Week 6	Number Analyzed	64 participants
		-6.77 (19.63)
Nausea and vomiting: Week 9	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Week 12	Number Analyzed	54 participants
		-8.02 (21.66)
Nausea and vomiting: Week 15	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Week 18	Number Analyzed	51 participants
		-9.15 (19.81)
Nausea and vomiting: Week 21	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Week 24	Number Analyzed	42 participants
		-9.13 (18.48)
Nausea and vomiting: Week 27	Number Analyzed	2 participants
		-8.33 (11.79)
Nausea and vomiting: Week 30	Number Analyzed	39 participants
		-5.98 (17.31)
Nausea and vomiting: Week 33	Number Analyzed	3 participants
		11.11 (25.46)
Nausea and vomiting: Week 36	Number Analyzed	38 participants
		-7.46 (17.63)
Nausea and vomiting: Week 39	Number Analyzed	2 participants
		16.67 (23.57)
Nausea and vomiting: Week 42	Number Analyzed	36 participants
		-8.80 (18.47)
Nausea and vomiting: Week 45	Number Analyzed	4 participants
		4.17 (8.33)
Nausea and vomiting: Week 48	Number Analyzed	32 participants
		-9.38 (19.37)
Nausea and vomiting: Week 51	Number Analyzed	2 participants
		8.33 (11.79)
Nausea and vomiting: Week 54	Number Analyzed	32 participants
		-8.85 (19.85)
Nausea and vomiting: Week 57	Number Analyzed	5 participants
		6.67 (14.91)
Nausea and vomiting: Week 60	Number Analyzed	30 participants
		-6.67 (17.29)
Nausea and vomiting: Week 63	Number Analyzed	3 participants
		11.11 (19.25)
Nausea and vomiting: Week 66	Number Analyzed	26 participants
		-7.05 (20.10)
Nausea and vomiting: Week 69	Number Analyzed	4 participants
		0.00 (0.00)
Nausea and vomiting: Week 72	Number Analyzed	23 participants
		-5.80 (19.85)
Nausea and vomiting: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Nausea and vomiting: Week 78	Number Analyzed	21 participants
		-5.56 (13.26)
Nausea and vomiting: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Nausea and vomiting: Week 84	Number Analyzed	13 participants
		-6.41 (12.80)
Nausea and vomiting: Week 87	Number Analyzed	3 participants
		5.56 (9.62)
Nausea and vomiting: Week 90	Number Analyzed	8 participants
		2.08 (13.91)
Nausea and vomiting: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Nausea and vomiting: Week 96	Number Analyzed	3 participants
		0.00 (16.67)
Nausea and vomiting: Week 99	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Week 105	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Week 111	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Week 117	Number Analyzed	1 participants
		0.00
Nausea and vomiting: Last visit	Number Analyzed	73 participants
		-6.85 (20.38)
Pain: Baseline	Number Analyzed	79 participants
		36.29 (33.63)
Pain: Week 6	Number Analyzed	64 participants
		-12.50 (33.47)
Pain: Week 9	Number Analyzed	1 participants
		0.00
Pain: Week 12	Number Analyzed	54 participants
		-14.81 (32.48)
Pain: Week 15	Number Analyzed	1 participants
		0.00
Pain: Week 18	Number Analyzed	51 participants
		-13.07 (33.55)
Pain: Week 21	Number Analyzed	1 participants
		0.00
Pain: Week 24	Number Analyzed	42 participants
		-6.35 (31.44)
Pain: Week 27	Number Analyzed	2 participants
		8.33 (11.79)
Pain: Week 30	Number Analyzed	39 participants
		-5.13 (33.37)
Pain: Week 33	Number Analyzed	3 participants
		5.56 (9.62)
Pain: Week 36	Number Analyzed	38 participants
		-6.14 (34.31)
Pain: Week 39	Number Analyzed	2 participants
		-8.33 (11.79)
Pain: Week 42	Number Analyzed	36 participants
		-5.09 (23.17)
Pain: Week 45	Number Analyzed	4 participants
		8.33 (21.52)
Pain: Week 48	Number Analyzed	33 participants
		-4.55 (17.81)
Pain: Week 51	Number Analyzed	2 participants
		-25.00 (11.79)
Pain: Week 54	Number Analyzed	32 participants
		-0.52 (24.86)
Pain: Week 57	Number Analyzed	5 participants
		0.00 (39.09)
Pain: Week 60	Number Analyzed	30 participants
		0.56 (14.17)
Pain: Week 63	Number Analyzed	3 participants
		-5.56 (9.62)
Pain: Week 66	Number Analyzed	26 participants
		-5.13 (23.46)
Pain: Week 69	Number Analyzed	4 participants
		-4.17 (15.96)
Pain: Week 72	Number Analyzed	23 participants
		-5.07 (28.62)
Pain: Week 75	Number Analyzed	2 participants
		-8.33 (11.79)
Pain: Week 78	Number Analyzed	21 participants
		1.59 (15.73)
Pain: Week 81	Number Analyzed	2 participants
		-8.33 (11.79)
Pain: Week 84	Number Analyzed	13 participants
		-5.13 (19.70)
Pain: Week 87	Number Analyzed	3 participants
		-5.56 (9.62)
Pain: Week 90	Number Analyzed	8 participants
		-8.33 (25.20)
Pain: Week 93	Number Analyzed	2 participants
		25.00 (35.36)
Pain: Week 96	Number Analyzed	3 participants
		-11.11 (53.58)
Pain: Week 99	Number Analyzed	1 participants
		0.00
Pain: Week 105	Number Analyzed	1 participants
		0.00
Pain: Week 111	Number Analyzed	1 participants
		0.00
Pain: Week 117	Number Analyzed	1 participants
		0.00
Pain: Last visit	Number Analyzed	73 participants
		-9.36 (29.92)
Dyspnoea: Baseline	Number Analyzed	78 participants
		33.33 (30.86)
Dyspnoea: Week 6	Number Analyzed	63 participants
		-12.17 (32.96)
Dyspnoea : Week 9	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 12	Number Analyzed	53 participants
		-10.69 (32.54)
Dyspnoea: Week 15	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 18	Number Analyzed	50 participants
		-12.67 (30.78)
Dyspnoea: Week 21	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 24	Number Analyzed	40 participants
		-7.50 (25.58)
Dyspnoea: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Dyspnoea: Week 30	Number Analyzed	38 participants
		-7.89 (26.21)
Dyspnoea: Week 33	Number Analyzed	3 participants
		0.00 (33.33)
Dyspnoea: Week 36	Number Analyzed	37 participants
		-7.21 (27.37)
Dyspnoea: Week 39	Number Analyzed	2 participants
		-16.67 (23.57)
Dyspnoea: Week 42	Number Analyzed	35 participants
		-5.71 (27.40)
Dyspnoea: Week 45	Number Analyzed	4 participants
		0.00 (27.22)
Dyspnoea: Week 48	Number Analyzed	32 participants
		-6.25 (28.63)
Dyspnoea: Week 51	Number Analyzed	2 participants
		0.00 (0.00)
Dyspnoea: Week 54	Number Analyzed	32 participants
		-7.29 (23.55)
Dyspnoea: Week 57	Number Analyzed	5 participants
		-6.67 (14.91)
Dyspnoea: Week 60	Number Analyzed	30 participants
		-1.11 (22.29)
Dyspnoea: Week 63	Number Analyzed	3 participants
		-11.11 (19.25)
Dyspnoea: Week 66	Number Analyzed	26 participants
		-8.97 (24.14)
Dyspnoea: Week 69	Number Analyzed	4 participants
		-8.33 (16.67)
Dyspnoea: Week 72	Number Analyzed	23 participants
		-1.45 (32.53)
Dyspnoea: Week 75	Number Analyzed	2 participants
		-16.67 (23.57)
Dyspnoea: Week 78	Number Analyzed	21 participants
		-4.76 (21.82)
Dyspnoea: Week 81	Number Analyzed	2 participants
		-16.67 (23.57)
Dyspnoea: Week 84	Number Analyzed	13 participants
		0.00 (23.57)
Dyspnoea: Week 87	Number Analyzed	3 participants
		-11.11 (19.25)
Dyspnoea: Week 90	Number Analyzed	8 participants
		8.33 (29.55)
Dyspnoea: Week 93	Number Analyzed	2 participants
		16.67 (23.57)
Dyspnoea: Week 96	Number Analyzed	3 participants
		-11.11 (38.49)
Dyspnoea: Week 99	Number Analyzed	1 participants
		33.33
Dyspnoea: Week 105	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 111	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 117	Number Analyzed	1 participants
		0.00
Dyspnoea: Last visit	Number Analyzed	72 participants
		-4.63 (33.71)
Insomnia: Baseline	Number Analyzed	79 participants
		31.22 (30.82)
Insomnia: Week 6	Number Analyzed	64 participants
		-9.38 (29.38)
Insomnia: Week 9	Number Analyzed	1 participants
		0.00
Insomnia: Week 12	Number Analyzed	54 participants
		-9.26 (34.52)
Insomnia: Week 15	Number Analyzed	1 participants
		0.00
Insomnia: Week 18	Number Analyzed	51 participants
		-3.27 (37.86)
Insomnia: Week 21	Number Analyzed	1 participants
		0.00
Insomnia: Week 24	Number Analyzed	42 participants
		-3.17 (36.67)
Insomnia: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Insomnia: Week 30	Number Analyzed	39 participants
		-9.40 (33.29)
Insomnia: Week 33	Number Analyzed	3 participants
		44.44 (50.92)
Insomnia: Week 36	Number Analyzed	38 participants
		-8.77 (40.03)
Insomnia: Week 39	Number Analyzed	2 participants
		83.33 (23.57)
Insomnia: Week 42	Number Analyzed	36 participants
		-5.56 (25.82)
Insomnia: Week 45	Number Analyzed	4 participants
		41.67 (31.91)
Insomnia: Week 48	Number Analyzed	32 participants
		-3.13 (29.77)
Insomnia: Week 51	Number Analyzed	2 participants
		50.00 (23.57)
Insomnia: Week 54	Number Analyzed	32 participants
		-2.08 (28.00)
Insomnia: Week 57	Number Analyzed	5 participants
		40.00 (43.46)
Insomnia: Week 60	Number Analyzed	30 participants
		-1.11 (28.34)
Insomnia: Week 63	Number Analyzed	3 participants
		0.00 (33.33)
Insomnia: Week 66	Number Analyzed	25 participants
		-5.33 (32.89)
Insomnia: Week 69	Number Analyzed	4 participants
		0.00 (27.22)
Insomnia: Week 72	Number Analyzed	23 participants
		0.00 (26.59)
Insomnia: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Insomnia: Week 78	Number Analyzed	21 participants
		1.59 (22.30)
Insomnia: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Insomnia: Week 84	Number Analyzed	13 participants
		0.00 (36.00)
Insomnia: Week 87	Number Analyzed	3 participants
		11.11 (19.25)
Insomnia: Week 90	Number Analyzed	8 participants
		0.00 (30.86)
Insomnia: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Insomnia: Week 96	Number Analyzed	3 participants
		22.22 (38.49)
Insomnia: Week 99	Number Analyzed	1 participants
		0.00
Insomnia: Week 105	Number Analyzed	1 participants
		0.00
Insomnia: Week 111	Number Analyzed	1 participants
		0.00
Insomnia: Week 117	Number Analyzed	1 participants
		0.00
Insomnia: Last visit	Number Analyzed	73 participants
		-1.83 (35.09)
Appetite loss: Baseline	Number Analyzed	79 participants
		29.96 (33.16)
Appetite loss: Week 6	Number Analyzed	64 participants
		-16.67 (30.28)
Appetite loss: Week 9	Number Analyzed	1 participants
		0.00
Appetite loss: Week 12	Number Analyzed	54 participants
		-18.52 (36.44)
Appetite loss: Week 15	Number Analyzed	1 participants
		0.00
Appetite loss: Week 18	Number Analyzed	51 participants
		-20.26 (33.39)
Appetite loss: Week 21	Number Analyzed	1 participants
		0.00
Appetite loss: Week 24	Number Analyzed	42 participants
		-19.84 (29.50)
Appetite loss: Week 27	Number Analyzed	2 participants
		-16.67 (23.57)
Appetite loss: Week 30	Number Analyzed	39 participants
		-13.68 (23.84)
Appetite loss: Week 33	Number Analyzed	3 participants
		-44.44 (19.25)
Appetite loss: Week 36	Number Analyzed	38 participants
		-14.91 (27.62)
Appetite loss: Week 39	Number Analyzed	2 participants
		-50.00 (23.57)
Appetite loss: Week 42	Number Analyzed	36 participants
		-16.67 (32.37)
Appetite loss: Week 45	Number Analyzed	4 participants
		-8.33 (41.94)
Appetite loss: Week 48	Number Analyzed	32 participants
		-20.83 (34.65)
Appetite loss: Week 51	Number Analyzed	2 participants
		-33.33 (47.14)
Appetite loss: Week 54	Number Analyzed	32 participants
		-18.75 (32.72)
Appetite loss: Week 57	Number Analyzed	5 participants
		-20.00 (29.81)
Appetite loss: Week 60	Number Analyzed	30 participants
		-20.00 (31.07)
Appetite loss: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Appetite loss: Week 66	Number Analyzed	26 participants
		-23.08 (33.69)
Appetite loss: Week 69	Number Analyzed	4 participants
		-16.67 (33.33)
Appetite loss: Week 72	Number Analyzed	23 participants
		-23.19 (30.87)
Appetite loss: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Appetite loss: Week 78	Number Analyzed	21 participants
		-20.63 (30.69)
Appetite loss: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Appetite loss: Week 84	Number Analyzed	13 participants
		-25.64 (36.40)
Appetite loss: Week 87	Number Analyzed	3 participants
		11.11 (19.25)
Appetite loss: Week 90	Number Analyzed	8 participants
		-20.83 (39.59)
Appetite loss: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Appetite loss: Week 96	Number Analyzed	3 participants
		-55.56 (50.92)
Appetite loss: Week 99	Number Analyzed	1 participants
		0.00
Appetite loss: Week 105	Number Analyzed	1 participants
		0.00
Appetite loss: Week 111	Number Analyzed	1 participants
		0.00
Appetite loss: Week 117	Number Analyzed	1 participants
		0.00
Appetite loss: Last visit	Number Analyzed	73 participants
		-13.70 (33.72)
Constipation: Baseline	Number Analyzed	79 participants
		20.25 (26.38)
Constipation: Week 6	Number Analyzed	64 participants
		9.90 (30.68)
Constipation: Week 9	Number Analyzed	1 participants
		0.00
Constipation: Week 12	Number Analyzed	54 participants
		1.85 (31.33)
Constipation: Week 15	Number Analyzed	1 participants
		33.33
Constipation: Week 18	Number Analyzed	51 participants
		4.58 (25.84)
Constipation: Week 21	Number Analyzed	1 participants
		0.00
Constipation: Week 24	Number Analyzed	42 participants
		2.38 (29.81)
Constipation: Week 27	Number Analyzed	2 participants
		33.33 (47.14)
Constipation: Week 30	Number Analyzed	39 participants
		5.13 (27.08)
Constipation: Week 33	Number Analyzed	3 participants
		11.11 (50.92)
Constipation: Week 36	Number Analyzed	38 participants
		5.26 (21.26)
Constipation: Week 39	Number Analyzed	2 participants
		16.67 (23.57)
Constipation: Week 42	Number Analyzed	36 participants
		9.26 (24.70)
Constipation: Week 45	Number Analyzed	4 participants
		50.00 (19.25)
Constipation: Week 48	Number Analyzed	32 participants
		1.04 (26.07)
Constipation: Week 51	Number Analyzed	2 participants
		-16.67 (23.57)
Constipation: Week 54	Number Analyzed	31 participants
		6.45 (23.44)
Constipation: Week 57	Number Analyzed	5 participants
		26.67 (43.46)
Constipation: Week 60	Number Analyzed	30 participants
		6.67 (22.15)
Constipation: Week 63	Number Analyzed	3 participants
		44.44 (38.49)
Constipation: Week 66	Number Analyzed	26 participants
		12.82 (26.79)
Constipation: Week 69	Number Analyzed	4 participants
		-8.33 (16.67)
Constipation: Week 72	Number Analyzed	23 participants
		4.35 (25.23)
Constipation: Week 75	Number Analyzed	2 participants
		33.33 (47.14)
Constipation: Week 78	Number Analyzed	21 participants
		7.94 (17.97)
Constipation: Week 81	Number Analyzed	2 participants
		33.33 (47.14)
Constipation: Week 84	Number Analyzed	13 participants
		7.69 (19.97)
Constipation: Week 87	Number Analyzed	3 participants
		22.22 (38.49)
Constipation: Week 90	Number Analyzed	8 participants
		8.33 (15.43)
Constipation: Week 93	Number Analyzed	2 participants
		33.33 (47.14)
Constipation: Week 96	Number Analyzed	3 participants
		-11.11 (50.92)
Constipation: Week 99	Number Analyzed	1 participants
		33.33
Constipation: Week 105	Number Analyzed	1 participants
		0.00
Constipation: Week 111	Number Analyzed	1 participants
		0.00
Constipation: Week 117	Number Analyzed	1 participants
		0.00
Constipation: Last visit	Number Analyzed	73 participants
		8.68 (31.93)
Diarrhoea: Baseline	Number Analyzed	78 participants
		13.25 (23.01)
Diarrhoea: Week 6	Number Analyzed	63 participants
		-7.41 (25.00)
Diarrhoea: Week 9	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 12	Number Analyzed	53 participants
		-6.29 (23.62)
Diarrhoea: Week 15	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 18	Number Analyzed	48 participants
		-5.56 (25.11)
Diarrhoea: Week 21	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 24	Number Analyzed	40 participants
		-4.17 (28.43)
Diarrhoea: Week 27	Number Analyzed	2 participants
		-16.67 (23.57)
Diarrhoea: Week 30	Number Analyzed	39 participants
		-8.55 (23.84)
Diarrhoea: Week 33	Number Analyzed	2 participants
		-16.67 (23.57)
Diarrhoea: Week 36	Number Analyzed	38 participants
		-7.89 (23.80)
Diarrhoea: Week 39	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 42	Number Analyzed	36 participants
		-6.48 (26.21)
Diarrhoea: Week 45	Number Analyzed	3 participants
		0.00 (0.00)
Diarrhoea: Week 48	Number Analyzed	33 participants
		-3.03 (28.09)
Diarrhoea: Week 51	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 54	Number Analyzed	32 participants
		-6.25 (26.01)
Diarrhoea: Week 57	Number Analyzed	4 participants
		0.00 (0.00)
Diarrhoea: Week 60	Number Analyzed	30 participants
		-1.11 (32.14)
Diarrhoea: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Diarrhoea: Week 66	Number Analyzed	26 participants
		-7.69 (30.27)
Diarrhoea: Week 69	Number Analyzed	3 participants
		11.11 (19.25)
Diarrhoea: Week 72	Number Analyzed	23 participants
		-7.25 (28.35)
Diarrhoea: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Diarrhoea: Week 78	Number Analyzed	20 participants
		-6.67 (25.59)
Diarrhoea: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Diarrhoea: Week 84	Number Analyzed	12 participants
		2.78 (26.43)
Diarrhoea: Week 87	Number Analyzed	3 participants
		11.11 (19.25)
Diarrhoea: Week 90	Number Analyzed	7 participants
		9.52 (16.27)
Diarrhoea: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Diarrhoea: Week 96	Number Analyzed	2 participants
		33.33 (47.14)
Diarrhoea: Week 99	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 105	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 111	Number Analyzed	1 participants
		0.00
Diarrhoea: Week 117	Number Analyzed	1 participants
		0.00
Diarrhoea: Last visit	Number Analyzed	72 participants
		-2.31 (28.15)
Financial difficulties: Baseline	Number Analyzed	79 participants
		30.80 (33.24)
Financial difficulties: Week 6	Number Analyzed	64 participants
		-2.60 (21.66)
Financial difficulties: Week 9	Number Analyzed	1 participants
		0.00
Financial difficulties: Week 12	Number Analyzed	54 participants
		-4.32 (23.39)
Financial difficulties: Week 15	Number Analyzed	1 participants
		0.00
Financial difficulties: Week 18	Number Analyzed	49 participants
		-4.76 (21.52)
Financial difficulties: Week 21	Number Analyzed	1 participants
		0.00
Financial difficulties: Week 24	Number Analyzed	41 participants
		-2.44 (26.24)
Financial difficulties: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Financial difficulties: Week 30	Number Analyzed	39 participants
		-6.84 (23.17)
Financial difficulties: Week 33	Number Analyzed	3 participants
		11.11 (19.25)
Financial difficulties: Week 36	Number Analyzed	38 participants
		-6.14 (27.79)
Financial difficulties: Week 39	Number Analyzed	2 participants
		16.67 (23.57)
Financial difficulties: Week 42	Number Analyzed	36 participants
		-6.48 (20.81)
Financial difficulties: Week 45	Number Analyzed	4 participants
		8.33 (16.67)
Financial difficulties: Week 48	Number Analyzed	33 participants
		-8.08 (23.61)
Financial difficulties: Week 51	Number Analyzed	2 participants
		16.67 (23.57)
Financial difficulties: Week 54	Number Analyzed	31 participants
		-2.15 (27.13)
Financial difficulties: Week 57	Number Analyzed	5 participants
		6.67 (14.91)
Financial difficulties: Week 60	Number Analyzed	30 participants
		-3.33 (22.06)
Financial difficulties: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Financial difficulties: Week 66	Number Analyzed	26 participants
		-2.56 (28.16)
Financial difficulties: Week 69	Number Analyzed	4 participants
		-8.33 (16.67)
Financial difficulties: Week 72	Number Analyzed	23 participants
		5.80 (25.92)
Financial difficulties: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Financial difficulties: Week 78	Number Analyzed	21 participants
		0.00 (34.96)
Financial difficulties: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Financial difficulties: Week 84	Number Analyzed	13 participants
		12.82 (34.80)
Financial difficulties: Week 87	Number Analyzed	3 participants
		0.00 (0.00)
Financial difficulties: Week 90	Number Analyzed	8 participants
		-4.17 (21.36)
Financial difficulties: Week 93	Number Analyzed	2 participants
		-16.67 (23.57)
Financial difficulties: Week 96	Number Analyzed	3 participants
		22.22 (38.49)
Financial difficulties: Week 99	Number Analyzed	1 participants
		0.00
Financial difficulties: Week 105	Number Analyzed	1 participants
		0.00
Financial difficulties: Week 111	Number Analyzed	1 participants
		0.00
Financial difficulties: Week 117	Number Analyzed	1 participants
		0.00
Financial difficulties: Last visit	Number Analyzed	73 participants
		1.83 (32.82)

28. Secondary Outcome

Title	Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II
Description	EORTC QLQ-LC13 consisted of 13 questions for dyspnea (3 items) and 10 single items (cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm/shoulder, other pain). Questions used 4-point scale (1 'Not at all' to 4 'Very much'). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below represents absolute data at baseline.
Time Frame	Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specified timepoint.

Arm/Group Title		Alectinib 600 mg (Fed): Phase II
Arm/Group Description:		Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Overall Number of Participants Analyzed		79
Mean (Standard Deviation); Unit of Measure: units on a scale
Dyspnoea: Baseline	Number Analyzed	76 participants
		30.85 (27.13)
Dyspnoea: Week 6	Number Analyzed	58 participants
		-8.24 (22.57)
Dyspnoea: Week 9	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 12	Number Analyzed	48 participants
		-7.64 (20.65)
Dyspnoea: Week 15	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 18	Number Analyzed	47 participants
		-11.35 (21.67)
Dyspnoea: Week 21	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 24	Number Analyzed	39 participants
		-7.41 (21.68)
Dyspnoea: Week 27	Number Analyzed	2 participants
		5.56 (7.86)
Dyspnoea: Week 30	Number Analyzed	38 participants
		-4.09 (20.41)
Dyspnoea: Week 33	Number Analyzed	3 participants
		-11.11 (11.11)
Dyspnoea: Week 36	Number Analyzed	37 participants
		-5.41 (21.69)
Dyspnoea: Week 39	Number Analyzed	2 participants
		-5.56 (7.86)
Dyspnoea: Week 42	Number Analyzed	36 participants
		-8.64 (20.25)
Dyspnoea: Week 45	Number Analyzed	4 participants
		-2.78 (27.78)
Dyspnoea: Week 48	Number Analyzed	33 participants
		-7.74 (24.77)
Dyspnoea: Week 51	Number Analyzed	2 participants
		-27.78 (23.57)
Dyspnoea: Week 54	Number Analyzed	31 participants
		-5.02 (19.63)
Dyspnoea: Week 57	Number Analyzed	5 participants
		-2.22 (16.48)
Dyspnoea: Week 60	Number Analyzed	29 participants
		-7.28 (19.54)
Dyspnoea: Week 63	Number Analyzed	3 participants
		3.70 (16.97)
Dyspnoea: Week 66	Number Analyzed	25 participants
		-6.22 (25.27)
Dyspnoea: Week 69	Number Analyzed	4 participants
		-13.89 (29.22)
Dyspnoea: Week 72	Number Analyzed	23 participants
		-6.76 (26.96)
Dyspnoea: Week 75	Number Analyzed	2 participants
		-5.56 (7.86)
Dyspnoea: Week 78	Number Analyzed	19 participants
		-8.19 (22.48)
Dyspnoea: Week 81	Number Analyzed	2 participants
		-5.56 (7.86)
Dyspnoea: Week 84	Number Analyzed	13 participants
		-9.40 (16.26)
Dyspnoea: Week 87	Number Analyzed	3 participants
		7.41 (23.13)
Dyspnoea: Week 90	Number Analyzed	8 participants
		-5.56 (17.82)
Dyspnoea: Week 93	Number Analyzed	2 participants
		22.22 (0.00)
Dyspnoea: Week 96	Number Analyzed	3 participants
		-51.85 (23.13)
Dyspnoea: Week 99	Number Analyzed	1 participants
		11.11
Dyspnoea: Week 105	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 111	Number Analyzed	1 participants
		0.00
Dyspnoea: Week 117	Number Analyzed	1 participants
		0.00
Dyspnoea: Last visit	Number Analyzed	69 participants
		-6.44 (23.45)
Coughing: Baseline	Number Analyzed	79 participants
		33.76 (27.47)
Coughing: Week 6	Number Analyzed	60 participants
		-13.89 (31.47)
Coughing: Week 9	Number Analyzed	1 participants
		0.00
Coughing: Week 12	Number Analyzed	52 participants
		-12.82 (27.34)
Coughing: Week 15	Number Analyzed	1 participants
		0.00
Coughing: Week 18	Number Analyzed	49 participants
		-13.61 (24.46)
Coughing: Week 21	Number Analyzed	1 participants
		0.00
Coughing: Week 24	Number Analyzed	40 participants
		-9.17 (31.11)
Coughing: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Coughing: Week 30	Number Analyzed	38 participants
		-1.75 (24.44)
Coughing: Week 33	Number Analyzed	3 participants
		-22.22 (19.25)
Coughing: Week 36	Number Analyzed	38 participants
		-8.77 (28.67)
Coughing: Week 39	Number Analyzed	2 participants
		-50.00 (23.57)
Coughing: Week 42	Number Analyzed	36 participants
		-0.93 (27.01)
Coughing: Week 45	Number Analyzed	4 participants
		-8.33 (50.00)
Coughing: Week 48	Number Analyzed	33 participants
		-4.04 (35.12)
Coughing: Week 51	Number Analyzed	2 participants
		-33.33 (0.00)
Coughing: Week 54	Number Analyzed	32 participants
		-8.33 (25.40)
Coughing: Week 57	Number Analyzed	5 participants
		-20.00 (29.81)
Coughing: Week 60	Number Analyzed	29 participants
		-2.30 (29.45)
Coughing: Week 63	Number Analyzed	3 participants
		0.00 (33.33)
Coughing: Week 66	Number Analyzed	26 participants
		-5.13 (27.80)
Coughing: Week 69	Number Analyzed	4 participants
		-25.00 (31.91)
Coughing: Week 72	Number Analyzed	23 participants
		-7.25 (28.35)
Coughing: Week 75	Number Analyzed	2 participants
		-16.67 (23.57)
Coughing: Week 78	Number Analyzed	20 participants
		-6.67 (35.21)
Coughing: Week 81	Number Analyzed	2 participants
		-16.67 (23.57)
Coughing: Week 84	Number Analyzed	13 participants
		-15.38 (29.24)
Coughing: Week 87	Number Analyzed	3 participants
		0.00 (33.33)
Coughing: Week 90	Number Analyzed	8 participants
		-8.33 (29.55)
Coughing: Week 93	Number Analyzed	2 participants
		16.67 (23.57)
Coughing: Week 96	Number Analyzed	3 participants
		-44.44 (19.25)
Coughing: Week 99	Number Analyzed	1 participants
		0.00
Coughing: Week 105	Number Analyzed	1 participants
		0.00
Coughing: Week 111	Number Analyzed	1 participants
		0.00
Coughing: Week 117	Number Analyzed	1 participants
		0.00
Coughing: Last visit	Number Analyzed	73 participants
		-5.48 (32.87)
Hemoptysis: Baseline	Number Analyzed	79 participants
		1.27 (6.41)
Hemoptysis: Week 6	Number Analyzed	60 participants
		-1.11 (6.03)
Hemoptysis: Week 9	Number Analyzed	1 participants
		0.00
Hemoptysis: Week 12	Number Analyzed	52 participants
		-1.28 (6.47)
Hemoptysis: Week 15	Number Analyzed	1 participants
		0.00
Hemoptysis: Week 18	Number Analyzed	49 participants
		-1.36 (6.66)
Hemoptysis: Week 21	Number Analyzed	1 participants
		0.00
Hemoptysis: Week 24	Number Analyzed	40 participants
		-1.67 (7.36)
Hemoptysis: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Hemoptysis: Week 30	Number Analyzed	39 participants
		0.00 (13.25)
Hemoptysis: Week 33	Number Analyzed	3 participants
		0.00 (0.00)
Hemoptysis: Week 36	Number Analyzed	38 participants
		-1.75 (7.54)
Hemoptysis: Week 39	Number Analyzed	2 participants
		0.00 (0.00)
Hemoptysis: Week 42	Number Analyzed	36 participants
		0.00 (7.97)
Hemoptysis: Week 45	Number Analyzed	4 participants
		0.00 (0.00)
Hemoptysis: Week 48	Number Analyzed	33 participants
		-1.01 (5.80)
Hemoptysis: Week 51	Number Analyzed	2 participants
		0.00 (0.00)
Hemoptysis: Week 54	Number Analyzed	31 participants
		1.08 (10.48)
Hemoptysis: Week 57	Number Analyzed	5 participants
		0.00 (0.00)
Hemoptysis: Week 60	Number Analyzed	29 participants
		-1.15 (6.19)
Hemoptysis: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Hemoptysis: Week 66	Number Analyzed	26 participants
		-1.28 (6.54)
Hemoptysis: Week 69	Number Analyzed	4 participants
		0.00 (0.00)
Hemoptysis: Week 72	Number Analyzed	23 participants
		2.90 (22.28)
Hemoptysis: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Hemoptysis: Week 78	Number Analyzed	20 participants
		-1.67 (7.45)
Hemoptysis: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Hemoptysis: Week 84	Number Analyzed	13 participants
		-2.56 (9.25)
Hemoptysis: Week 87	Number Analyzed	3 participants
		0.00 (0.00)
Hemoptysis: Week 90	Number Analyzed	8 participants
		0.00 (0.00)
Hemoptysis: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Hemoptysis: Week 96	Number Analyzed	3 participants
		0.00 (0.00)
Hemoptysis: Week 99	Number Analyzed	1 participants
		0.00
Hemoptysis: Week 105	Number Analyzed	1 participants
		0.00
Hemoptysis: Week 111	Number Analyzed	1 participants
		0.00
Hemoptysis: Week 117	Number Analyzed	1 participants
		0.00
Hemoptysis: Last visit	Number Analyzed	73 participants
		-0.91 (7.80)
Sore mouth: Baseline	Number Analyzed	79 participants
		5.06 (16.09)
Sore mouth: Week 6	Number Analyzed	60 participants
		-1.11 (13.68)
Sore mouth: Week 9	Number Analyzed	1 participants
		0.00
Sore mouth: Week 12	Number Analyzed	52 participants
		0.64 (13.99)
Sore mouth: Week 15	Number Analyzed	1 participants
		0.00
Sore mouth: Week 18	Number Analyzed	49 participants
		-2.04 (17.22)
Sore mouth: Week 21	Number Analyzed	1 participants
		0.00
Sore mouth: Week 24	Number Analyzed	39 participants
		-0.85 (17.91)
Sore mouth: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Sore mouth: Week 30	Number Analyzed	39 participants
		2.56 (11.81)
Sore mouth: Week 33	Number Analyzed	3 participants
		22.22 (38.49)
Sore mouth: Week 36	Number Analyzed	38 participants
		1.75 (15.40)
Sore mouth: Week 39	Number Analyzed	2 participants
		16.67 (23.57)
Sore mouth: Week 42	Number Analyzed	36 participants
		-0.93 (9.71)
Sore mouth: Week 45	Number Analyzed	4 participants
		0.00 (0.00)
Sore mouth: Week 48	Number Analyzed	33 participants
		7.07 (26.03)
Sore mouth: Week 51	Number Analyzed	2 participants
		0.00 (0.00)
Sore mouth: Week 54	Number Analyzed	31 participants
		1.08 (13.56)
Sore mouth: Week 57	Number Analyzed	5 participants
		0.00 (23.57)
Sore mouth: Week 60	Number Analyzed	29 participants
		-1.15 (14.04)
Sore mouth: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Sore mouth: Week 66	Number Analyzed	26 participants
		-2.56 (13.07)
Sore mouth: Week 69	Number Analyzed	4 participants
		0.00 (0.00)
Sore mouth: Week 72	Number Analyzed	22 participants
		4.55 (18.67)
Sore mouth: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Sore mouth: Week 78	Number Analyzed	20 participants
		1.67 (7.45)
Sore mouth: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Sore mouth: Week 84	Number Analyzed	13 participants
		0.00 (0.00)
Sore mouth: Week 87	Number Analyzed	3 participants
		0.00 (0.00)
Sore mouth: Week 90	Number Analyzed	8 participants
		4.17 (11.79)
Sore mouth: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Sore mouth: Week 96	Number Analyzed	3 participants
		11.11 (19.25)
Sore mouth: Week 99	Number Analyzed	1 participants
		0.00
Sore mouth: Week 105	Number Analyzed	1 participants
		0.00
Sore mouth: Week 111	Number Analyzed	1 participants
		0.00
Sore mouth: Week 117	Number Analyzed	1 participants
		0.00
Sore mouth: Last visit	Number Analyzed	73 participants
		-0.46 (15.21)
Dysphagia: Baseline	Number Analyzed	79 participants
		4.64 (11.61)
Dysphagia: Week 6	Number Analyzed	60 participants
		-1.67 (11.36)
Dysphagia: Week 9	Number Analyzed	1 participants
		0.00
Dysphagia: Week 12	Number Analyzed	52 participants
		-0.64 (10.42)
Dysphagia: Week 15	Number Analyzed	1 participants
		0.00
Dysphagia: Week 18	Number Analyzed	49 participants
		-1.36 (11.70)
Dysphagia: Week 21	Number Analyzed	1 participants
		0.00
Dysphagia: Week 24	Number Analyzed	40 participants
		0.83 (11.91)
Dysphagia: Week 27	Number Analyzed	2 participants
		16.67 (23.57)
Dysphagia: Week 30	Number Analyzed	39 participants
		3.42 (14.90)
Dysphagia: Week 33	Number Analyzed	3 participants
		0.00 (33.33)
Dysphagia: Week 36	Number Analyzed	38 participants
		-0.88 (5.41)
Dysphagia: Week 39	Number Analyzed	2 participants
		-16.67 (23.57)
Dysphagia: Week 42	Number Analyzed	36 participants
		-0.93 (12.56)
Dysphagia: Week 45	Number Analyzed	4 participants
		0.00 (27.22)
Dysphagia: Week 48	Number Analyzed	33 participants
		2.02 (16.54)
Dysphagia: Week 51	Number Analyzed	2 participants
		-16.67 (23.57)
Dysphagia: Week 54	Number Analyzed	31 participants
		-1.08 (13.56)
Dysphagia: Week 57	Number Analyzed	5 participants
		6.67 (27.89)
Dysphagia: Week 60	Number Analyzed	28 participants
		-3.57 (13.88)
Dysphagia: Week 63	Number Analyzed	3 participants
		11.11 (19.25)
Dysphagia: Week 66	Number Analyzed	26 participants
		-1.28 (14.85)
Dysphagia: Week 69	Number Analyzed	4 participants
		0.00 (0.00)
Dysphagia: Week 72	Number Analyzed	23 participants
		1.45 (15.82)
Dysphagia: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Dysphagia: Week 78	Number Analyzed	20 participants
		0.00 (10.81)
Dysphagia: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Dysphagia: Week 84	Number Analyzed	13 participants
		2.56 (9.25)
Dysphagia: Week 87	Number Analyzed	3 participants
		0.00 (0.00)
Dysphagia: Week 90	Number Analyzed	8 participants
		0.00 (0.00)
Dysphagia: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Dysphagia: Week 96	Number Analyzed	3 participants
		0.00 (0.00)
Dysphagia: Week 99	Number Analyzed	1 participants
		0.00
Dysphagia: Week 105	Number Analyzed	1 participants
		0.00
Dysphagia: Week 111	Number Analyzed	1 participants
		0.00
Dysphagia: Week 117	Number Analyzed	1 participants
		0.00
Dysphagia: Last visit	Number Analyzed	73 participants
		2.74 (17.35)
Peripheral neuropathy: Baseline	Number Analyzed	79 participants
		13.08 (22.28)
Peripheral neuropathy: Week 6	Number Analyzed	60 participants
		6.11 (17.88)
Peripheral neuropathy: Week 9	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Week 12	Number Analyzed	52 participants
		1.28 (20.83)
Peripheral neuropathy: Week 15	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Week 18	Number Analyzed	49 participants
		2.72 (22.40)
Peripheral neuropathy: Week 21	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Week 24	Number Analyzed	40 participants
		4.17 (20.24)
Peripheral neuropathy: Week 27	Number Analyzed	2 participants
		-16.67 (23.57)
Peripheral neuropathy: Week 30	Number Analyzed	39 participants
		4.27 (24.40)
Peripheral neuropathy: Week 33	Number Analyzed	3 participants
		11.11 (19.25)
Peripheral neuropathy: Week 36	Number Analyzed	38 participants
		0.00 (18.98)
Peripheral neuropathy: Week 39	Number Analyzed	2 participants
		0.00 (0.00)
Peripheral neuropathy: Week 42	Number Analyzed	36 participants
		1.85 (21.00)
Peripheral neuropathy: Week 45	Number Analyzed	4 participants
		8.33 (16.67)
Peripheral neuropathy: Week 48	Number Analyzed	33 participants
		2.02 (23.48)
Peripheral neuropathy: Week 51	Number Analyzed	2 participants
		0.00 (0.00)
Peripheral neuropathy: Week 54	Number Analyzed	31 participants
		6.45 (26.41)
Peripheral neuropathy: Week 57	Number Analyzed	5 participants
		6.67 (27.89)
Peripheral neuropathy: Week 60	Number Analyzed	29 participants
		2.30 (23.45)
Peripheral neuropathy: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Peripheral neuropathy: Week 66	Number Analyzed	26 participants
		1.28 (24.00)
Peripheral neuropathy: Week 69	Number Analyzed	4 participants
		0.00 (0.00)
Peripheral neuropathy: Week 72	Number Analyzed	23 participants
		2.90 (28.27)
Peripheral neuropathy: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Peripheral neuropathy: Week 78	Number Analyzed	20 participants
		-3.33 (21.36)
Peripheral neuropathy: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Peripheral neuropathy: Week 84	Number Analyzed	13 participants
		12.82 (37.36)
Peripheral neuropathy: Week 87	Number Analyzed	3 participants
		0.00 (0.00)
Peripheral neuropathy: Week 90	Number Analyzed	8 participants
		16.67 (17.82)
Peripheral neuropathy: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Peripheral neuropathy: Week 96	Number Analyzed	3 participants
		55.56 (38.49)
Peripheral neuropathy: Week 99	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Week 105	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Week 111	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Week 117	Number Analyzed	1 participants
		0.00
Peripheral neuropathy: Last visit	Number Analyzed	73 participants
		1.37 (22.52)
Alopecia: Baseline	Number Analyzed	77 participants
		11.69 (25.80)
Alopecia: Week 6	Number Analyzed	59 participants
		-1.13 (22.29)
Alopecia: Week 9	Number Analyzed	1 participants
		0.00
Alopecia: Week 12	Number Analyzed	51 participants
		1.31 (31.24)
Alopecia: Week 15	Number Analyzed	1 participants
		0.00
Alopecia: Week 18	Number Analyzed	47 participants
		-4.96 (25.04)
Alopecia: Week 21	Number Analyzed	1 participants
		0.00
Alopecia: Week 24	Number Analyzed	39 participants
		-2.56 (27.98)
Alopecia: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Alopecia: Week 30	Number Analyzed	38 participants
		-3.51 (27.72)
Alopecia: Week 33	Number Analyzed	3 participants
		0.00 (0.00)
Alopecia: Week 36	Number Analyzed	37 participants
		0.90 (32.85)
Alopecia: Week 39	Number Analyzed	2 participants
		0.00 (0.00)
Alopecia: Week 42	Number Analyzed	36 participants
		-2.78 (20.12)
Alopecia: Week 45	Number Analyzed	4 participants
		0.00 (0.00)
Alopecia: Week 48	Number Analyzed	32 participants
		-5.21 (22.58)
Alopecia: Week 51	Number Analyzed	2 participants
		0.00 (0.00)
Alopecia: Week 54	Number Analyzed	31 participants
		-6.45 (15.91)
Alopecia: Week 57	Number Analyzed	5 participants
		-6.67 (14.91)
Alopecia: Week 60	Number Analyzed	29 participants
		-4.60 (19.36)
Alopecia: Week 63	Number Analyzed	3 participants
		-11.11 (19.25)
Alopecia: Week 66	Number Analyzed	25 participants
		-2.67 (27.08)
Alopecia: Week 69	Number Analyzed	4 participants
		-8.33 (16.67)
Alopecia: Week 72	Number Analyzed	22 participants
		-3.03 (33.98)
Alopecia: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Alopecia: Week 78	Number Analyzed	20 participants
		-8.33 (26.21)
Alopecia: Week 81	Number Analyzed	2 participants
		-16.67 (23.57)
Alopecia: Week 84	Number Analyzed	13 participants
		-2.56 (25.32)
Alopecia: Week 87	Number Analyzed	3 participants
		-11.11 (19.25)
Alopecia: Week 90	Number Analyzed	8 participants
		4.17 (21.36)
Alopecia: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Alopecia: Week 96	Number Analyzed	3 participants
		0.00 (0.00)
Alopecia: Week 99	Number Analyzed	1 participants
		0.00
Alopecia: Week 105	Number Analyzed	1 participants
		0.00
Alopecia: Week 111	Number Analyzed	1 participants
		0.00
Alopecia: Week 117	Number Analyzed	1 participants
		0.00
Alopecia: Last visit	Number Analyzed	71 participants
		-5.16 (27.97)
Pain in chest: Baseline	Number Analyzed	79 participants
		21.52 (28.26)
Pain in chest: Week 6	Number Analyzed	60 participants
		-16.67 (29.75)
Pain in chest: Week 9	Number Analyzed	1 participants
		0.00
Pain in chest: Week 12	Number Analyzed	52 participants
		-11.54 (23.69)
Pain in chest: Week 15	Number Analyzed	1 participants
		0.00
Pain in chest: Week 18	Number Analyzed	49 participants
		-8.84 (27.87)
Pain in chest: Week 21	Number Analyzed	1 participants
		0.00
Pain in chest: Week 24	Number Analyzed	40 participants
		-8.33 (23.57)
Pain in chest: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Pain in chest: Week 30	Number Analyzed	39 participants
		-3.42 (22.68)
Pain in chest: Week 33	Number Analyzed	3 participants
		-11.11 (19.25)
Pain in chest: Week 36	Number Analyzed	38 participants
		-6.14 (26.68)
Pain in chest: Week 39	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in chest: Week 42	Number Analyzed	36 participants
		-6.48 (19.22)
Pain in chest: Week 45	Number Analyzed	4 participants
		-8.33 (41.94)
Pain in chest: Week 48	Number Analyzed	33 participants
		-6.06 (19.46)
Pain in chest: Week 51	Number Analyzed	2 participants
		-33.33 (0.00)
Pain in chest: Week 54	Number Analyzed	31 participants
		-4.30 (20.62)
Pain in chest: Week 57	Number Analyzed	5 participants
		-13.33 (38.01)
Pain in chest: Week 60	Number Analyzed	29 participants
		-3.45 (16.29)
Pain in chest: Week 63	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in chest: Week 66	Number Analyzed	26 participants
		-2.56 (18.67)
Pain in chest: Week 69	Number Analyzed	4 participants
		-25.00 (31.91)
Pain in chest: Week 72	Number Analyzed	23 participants
		-2.90 (28.27)
Pain in chest: Week 75	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in chest: Week 78	Number Analyzed	20 participants
		0.00 (18.73)
Pain in chest: Week 81	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in chest: Week 84	Number Analyzed	13 participants
		-5.13 (22.96)
Pain in chest: Week 87	Number Analyzed	3 participants
		-11.11 (19.25)
Pain in chest: Week 90	Number Analyzed	8 participants
		-12.50 (24.80)
Pain in chest: Week 93	Number Analyzed	2 participants
		16.67 (23.57)
Pain in chest: Week 96	Number Analyzed	3 participants
		-22.22 (19.25)
Pain in chest: Week 99	Number Analyzed	1 participants
		0.00
Pain in chest: Week 105	Number Analyzed	1 participants
		0.00
Pain in chest: Week 111	Number Analyzed	1 participants
		0.00
Pain in chest: Week 117	Number Analyzed	1 participants
		0.00
Pain in chest: Last visit	Number Analyzed	72 participants
		-8.80 (26.83)
Pain in arm or shoulder: Baseline	Number Analyzed	79 participants
		16.88 (28.18)
Pain in arm or shoulder: Week 6	Number Analyzed	60 participants
		-7.22 (25.37)
Pain in arm or shoulder: Week 9	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Week 12	Number Analyzed	52 participants
		-5.77 (30.05)
Pain in arm or shoulder: Week 15	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Week 18	Number Analyzed	48 participants
		-4.86 (24.78)
Pain in arm or shoulder: Week 21	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Week 24	Number Analyzed	40 participants
		-10.83 (27.62)
Pain in arm or shoulder: Week 27	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in arm or shoulder: Week 30	Number Analyzed	39 participants
		-3.42 (23.93)
Pain in arm or shoulder: Week 33	Number Analyzed	3 participants
		-11.11 (38.49)
Pain in arm or shoulder: Week 36	Number Analyzed	38 participants
		-5.26 (33.36)
Pain in arm or shoulder: Week 39	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in arm or shoulder: Week 42	Number Analyzed	36 participants
		-5.56 (25.82)
Pain in arm or shoulder: Week 45	Number Analyzed	4 participants
		0.00 (0.00)
Pain in arm or shoulder: Week 48	Number Analyzed	33 participants
		-6.06 (21.17)
Pain in arm or shoulder: Week 51	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in arm or shoulder: Week 54	Number Analyzed	31 participants
		-1.08 (25.07)
Pain in arm or shoulder: Week 57	Number Analyzed	5 participants
		0.00 (23.57)
Pain in arm or shoulder: Week 60	Number Analyzed	29 participants
		-2.30 (26.62)
Pain in arm or shoulder: Week 63	Number Analyzed	3 participants
		0.00 (0.00)
Pain in arm or shoulder: Week 66	Number Analyzed	26 participants
		-3.85 (27.21)
Pain in arm or shoulder: Week 69	Number Analyzed	4 participants
		-16.67 (33.33)
Pain in arm or shoulder: Week 72	Number Analyzed	23 participants
		-4.35 (28.96)
Pain in arm or shoulder: Week 75	Number Analyzed	2 participants
		0.00 (0.00)
Pain in arm or shoulder: Week 78	Number Analyzed	19 participants
		-8.77 (24.45)
Pain in arm or shoulder: Week 81	Number Analyzed	2 participants
		0.00 (0.00)
Pain in arm or shoulder: Week 84	Number Analyzed	13 participants
		7.69 (38.86)
Pain in arm or shoulder: Week 87	Number Analyzed	3 participants
		0.00 (0.00)
Pain in arm or shoulder: Week 90	Number Analyzed	8 participants
		4.17 (21.36)
Pain in arm or shoulder: Week 93	Number Analyzed	2 participants
		0.00 (0.00)
Pain in arm or shoulder: Week 96	Number Analyzed	3 participants
		0.00 (33.33)
Pain in arm or shoulder: Week 99	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Week 105	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Week 111	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Week 117	Number Analyzed	1 participants
		0.00
Pain in arm or shoulder: Last visit	Number Analyzed	73 participants
		0.00 (29.92)
Pain in other parts: Baseline	Number Analyzed	75 participants
		44.00 (36.42)
Pain in other parts: Week 6	Number Analyzed	57 participants
		-16.96 (42.78)
Pain in other parts: Week 9	Number Analyzed	1 participants
		0.00
Pain in other parts: Week 12	Number Analyzed	46 participants
		-11.59 (41.70)
Pain in other parts: Week 15	Number Analyzed	1 participants
		0.00
Pain in other parts: Week 18	Number Analyzed	45 participants
		-19.26 (41.74)
Pain in other parts: Week 21	Number Analyzed	1 participants
		0.00
Pain in other parts: Week 24	Number Analyzed	38 participants
		-19.30 (36.87)
Pain in other parts: Week 27	Number Analyzed	2 participants
		0.00 (0.00)
Pain in other parts: Week 30	Number Analyzed	36 participants
		-18.52 (37.75)
Pain in other parts: Week 33	Number Analyzed	3 participants
		0.00 (33.33)
Pain in other parts: Week 36	Number Analyzed	36 participants
		-18.52 (36.90)
Pain in other parts: Week 39	Number Analyzed	2 participants
		0.00 (94.28)
Pain in other parts: Week 42	Number Analyzed	33 participants
		-16.16 (37.38)
Pain in other parts: Week 45	Number Analyzed	4 participants
		-8.33 (56.93)
Pain in other parts: Week 48	Number Analyzed	30 participants
		-12.22 (34.45)
Pain in other parts: Week 51	Number Analyzed	2 participants
		0.00 (47.14)
Pain in other parts: Week 54	Number Analyzed	29 participants
		-14.94 (38.41)
Pain in other parts: Week 57	Number Analyzed	5 participants
		-13.33 (38.01)
Pain in other parts: Week 60	Number Analyzed	26 participants
		-15.38 (34.29)
Pain in other parts: Week 63	Number Analyzed	3 participants
		-44.44 (38.49)
Pain in other parts: Week 66	Number Analyzed	22 participants
		-10.61 (39.02)
Pain in other parts: Week 69	Number Analyzed	4 participants
		-8.33 (41.94)
Pain in other parts: Week 72	Number Analyzed	20 participants
		-15.00 (33.29)
Pain in other parts: Week 75	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in other parts: Week 78	Number Analyzed	19 participants
		-5.26 (27.81)
Pain in other parts: Week 81	Number Analyzed	2 participants
		-16.67 (23.57)
Pain in other parts: Week 84	Number Analyzed	11 participants
		-12.12 (22.47)
Pain in other parts: Week 87	Number Analyzed	3 participants
		-22.22 (38.49)
Pain in other parts: Week 90	Number Analyzed	6 participants
		0.00 (36.51)
Pain in other parts: Week 93	Number Analyzed	2 participants
		33.33 (47.14)
Pain in other parts: Week 96	Number Analyzed	1 participants
		-33.33
Pain in other parts: Week 99	Number Analyzed	1 participants
		0.00
Pain in other parts: Week 105	Number Analyzed	1 participants
		0.00
Pain in other parts: Week 111	Number Analyzed	1 participants
		0.00
Pain in other parts: Week 117	Number Analyzed	1 participants
		0.00
Pain in other parts: Last visit	Number Analyzed	69 participants
		-12.56 (37.96)

Adverse Events

Time Frame	Baseline to up to 28 days after the last dose of alectinib (up to 284 weeks)
Adverse Event Reporting Description	Safety population
Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
All-Cause Mortality
	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase II
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/7 (100.00%)	4/7 (57.14%)	6/13 (46.15%)	2/7 (28.57%)	9/13 (69.23%)	45/87 (51.72%)
Serious Adverse Events
	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase II
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/7 (14.29%)	2/7 (28.57%)	6/13 (46.15%)	0/7 (0.00%)	1/13 (7.69%)	21/87 (24.14%)
Blood and lymphatic system disorders
Anaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Cardiac disorders
Pericardial effusion * 1	0/7 (0.00%)	0/7 (0.00%)	2/13 (15.38%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Ear and labyrinth disorders
Vertigo * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gastrointestinal disorders
Nausea * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Vomiting * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Intestinal obstruction * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
General disorders
Fatigue * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Non-cardiac chest pain * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Death * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Hepatobiliary disorders
Drug-induced liver injury * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Bile duct obstruction * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Infections and infestations
Bronchitis * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Pneumonia bacterial * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Influenza * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Lung infection * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Staphylococcal sepsis * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Pneumonia * 1	0/7 (0.00%)	0/7 (0.00%)	2/13 (15.38%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Gastroenteritis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Injury, poisoning and procedural complications
Procedural pain * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Overdose * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Radiation necrosis * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Stroke-like migraine attacks after radiation therapy * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Metabolism and nutrition disorders
Hyperammonaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Hyponatraemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Tumour necrosis * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Nervous system disorders
Brain oedema * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Cerebral ventricle dilatation * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Embolic stroke * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Haemorrhage intracranial * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Hemiparesis * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Seizure * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Cerebrovascular accident * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Headache * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Renal and urinary disorders
Renal failure * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Chronic obstructive pulmonary disease * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Hypercapnia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Pneumothorax * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Vascular disorders
Haemorrhage * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/87 (1.15%)
Embolism * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
1 Term from vocabulary, MedDRA Version 20.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase II
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/7 (100.00%)	7/7 (100.00%)	12/13 (92.31%)	7/7 (100.00%)	13/13 (100.00%)	85/87 (97.70%)
Blood and lymphatic system disorders
Anaemia * 1	1/7 (14.29%)	3/7 (42.86%)	0/13 (0.00%)	1/7 (14.29%)	4/13 (30.77%)	17/87 (19.54%)
Leukopenia * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	6/87 (6.90%)
Neutropenia * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Thrombocytopenia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Cardiac disorders
Sinus bradycardia * 1	0/7 (0.00%)	0/7 (0.00%)	4/13 (30.77%)	2/7 (28.57%)	0/13 (0.00%)	6/87 (6.90%)
Atrial fibrillation * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Atrioventricular block * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Bradycardia * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	8/87 (9.20%)
Bundle branch block left * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Cardiomyopathy * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Coronary artery disease * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Diastolic dysfunction * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Ventricular extrasystoles * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Ear and labyrinth disorders
Tinnitus * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Vertigo * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hypoacusis * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Endocrine disorders
Hypothyroidism * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Eye disorders
Visual impairment * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Eye irritation * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Eyelid oedema * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Periorbital oedema * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Vision blurred * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	7/87 (8.05%)
Vitreous floaters * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gastrointestinal disorders
Constipation * 1	0/7 (0.00%)	2/7 (28.57%)	3/13 (23.08%)	3/7 (42.86%)	3/13 (23.08%)	34/87 (39.08%)
Nausea * 1	2/7 (28.57%)	2/7 (28.57%)	3/13 (23.08%)	0/7 (0.00%)	3/13 (23.08%)	22/87 (25.29%)
Diarrhoea * 1	0/7 (0.00%)	2/7 (28.57%)	2/13 (15.38%)	1/7 (14.29%)	3/13 (23.08%)	21/87 (24.14%)
Vomiting * 1	1/7 (14.29%)	1/7 (14.29%)	2/13 (15.38%)	0/7 (0.00%)	0/13 (0.00%)	14/87 (16.09%)
Abdominal discomfort * 1	1/7 (14.29%)	0/7 (0.00%)	2/13 (15.38%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Abdominal pain * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	2/13 (15.38%)	0/87 (0.00%)
Abdominal distension * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Abdominal pain upper * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Dry mouth * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	5/87 (5.75%)
Flatulence * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Abdominal pain lower * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Dental caries * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Haemorrhoids * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Oral disorder * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Stomatitis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Faecaloma * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gastrooesophageal reflux disease * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gingival swelling * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Noninfective gingivitis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Oesophagitis * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
General disorders
Fatigue * 1	4/7 (57.14%)	3/7 (42.86%)	3/13 (23.08%)	5/7 (71.43%)	7/13 (53.85%)	36/87 (41.38%)
Oedema peripheral * 1	1/7 (14.29%)	1/7 (14.29%)	2/13 (15.38%)	2/7 (28.57%)	3/13 (23.08%)	22/87 (25.29%)
Pain * 1	0/7 (0.00%)	0/7 (0.00%)	3/13 (23.08%)	0/7 (0.00%)	1/13 (7.69%)	9/87 (10.34%)
Pyrexia * 1	0/7 (0.00%)	1/7 (14.29%)	2/13 (15.38%)	0/7 (0.00%)	0/13 (0.00%)	5/87 (5.75%)
Asthenia * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Chest discomfort * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Chest pain * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	5/87 (5.75%)
Face oedema * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gait disturbance * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Injection site haemorrhage * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Injection site reaction * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Mucosal inflammation * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Non-cardiac chest pain * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Axillary pain * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Influenza like illness * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Oedema * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Peripheral swelling * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Hepatobiliary disorders
Hyperbilirubinaemia * 1	0/7 (0.00%)	2/7 (28.57%)	2/13 (15.38%)	0/7 (0.00%)	2/13 (15.38%)	7/87 (8.05%)
Infections and infestations
Upper respiratory tract infection * 1	1/7 (14.29%)	2/7 (28.57%)	3/13 (23.08%)	0/7 (0.00%)	1/13 (7.69%)	14/87 (16.09%)
Urinary tract infection * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	2/13 (15.38%)	9/87 (10.34%)
Pneumonia * 1	0/7 (0.00%)	0/7 (0.00%)	3/13 (23.08%)	0/7 (0.00%)	1/13 (7.69%)	6/87 (6.90%)
Oral herpes * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/87 (0.00%)
Tooth infection * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Viral upper respiratory tract infection * 1	0/7 (0.00%)	2/7 (28.57%)	2/13 (15.38%)	3/7 (42.86%)	0/13 (0.00%)	5/87 (5.75%)
Conjunctivitis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Fungal skin infection * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gastroenteritis viral * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Rash pustular * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Rhinitis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Sinusitis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Viral infection * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Babesiosis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Infective exacerbation of chronic obstructive airways disease * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Influenza * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Onychomycosis * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Injury, poisoning and procedural complications
Excoriation * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Fall * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	5/87 (5.75%)
Post lumbar puncture syndrome * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Radiation injury * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Thermal burn * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Upper limb fracture * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Animal bite * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Fractured sacrum * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Investigations
Blood creatine phosphokinase increased * 1	0/7 (0.00%)	4/7 (57.14%)	1/13 (7.69%)	4/7 (57.14%)	1/13 (7.69%)	20/87 (22.99%)
Alanine aminotransferase increased * 1	1/7 (14.29%)	3/7 (42.86%)	3/13 (23.08%)	2/7 (28.57%)	1/13 (7.69%)	16/87 (18.39%)
Aspartate aminotransferase increased * 1	1/7 (14.29%)	3/7 (42.86%)	2/13 (15.38%)	2/7 (28.57%)	1/13 (7.69%)	18/87 (20.69%)
Blood bilirubin increased * 1	0/7 (0.00%)	1/7 (14.29%)	3/13 (23.08%)	1/7 (14.29%)	2/13 (15.38%)	10/87 (11.49%)
Blood creatinine increased * 1	0/7 (0.00%)	1/7 (14.29%)	4/13 (30.77%)	1/7 (14.29%)	0/13 (0.00%)	5/87 (5.75%)
Blood alkaline phosphatase increased * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	1/7 (14.29%)	1/13 (7.69%)	12/87 (13.79%)
Electrocardiogram PR Prolongation * 1	0/7 (0.00%)	0/7 (0.00%)	2/13 (15.38%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Neutrophil count decreased * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/87 (0.00%)
White blood cell count decreased * 1	1/7 (14.29%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Blood lactate dehydrogenase increased * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Blood triglycerides increased * 1	0/7 (0.00%)	2/7 (28.57%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Gamma-glutamyltransferase increased * 1	1/7 (14.29%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Haemoglobin decreased * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Activated partial thromboplastin time prolonged * 1	0/7 (0.00%)	0/7 (0.00%)	2/13 (15.38%)	0/7 (0.00%)	0/13 (0.00%)	8/87 (9.20%)
Blood cholesterol increased * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Blood phosphorus increased * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Ejection fraction decreased * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Heart rate irregular * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
International normalised ratio increased * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Neutrophil count * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Platelet count decreased * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Weight decreased * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	6/87 (6.90%)
Weight increased * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	17/87 (19.54%)
Blood testosterone decreased * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Electrocardiogram abnormal * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Prothrombin time prolonged * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Metabolism and nutrition disorders
Hyperglycaemia * 1	0/7 (0.00%)	2/7 (28.57%)	1/13 (7.69%)	3/7 (42.86%)	0/13 (0.00%)	6/87 (6.90%)
Hypertriglyceridaemia * 1	0/7 (0.00%)	0/7 (0.00%)	2/13 (15.38%)	3/7 (42.86%)	1/13 (7.69%)	13/87 (14.94%)
Hypophosphataemia * 1	0/7 (0.00%)	2/7 (28.57%)	1/13 (7.69%)	1/7 (14.29%)	1/13 (7.69%)	6/87 (6.90%)
Hypokalaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	3/13 (23.08%)	10/87 (11.49%)
Decreased appetite * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	9/87 (10.34%)
Fluid retention * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/87 (0.00%)
Dyslipidaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Hyperkalaemia * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hypoalbuminaemia * 1	0/7 (0.00%)	2/7 (28.57%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	6/87 (6.90%)
Hypocalcaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Hypomagnesaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Hyponatraemia * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hypercalcaemia * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hypercholesterolaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Hyperphosphataemia * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hypoglycaemia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Musculoskeletal and connective tissue disorders
Myalgia * 1	1/7 (14.29%)	4/7 (57.14%)	2/13 (15.38%)	3/7 (42.86%)	2/13 (15.38%)	23/87 (26.44%)
Arthralgia * 1	2/7 (28.57%)	1/7 (14.29%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	12/87 (13.79%)
Back pain * 1	1/7 (14.29%)	1/7 (14.29%)	5/13 (38.46%)	2/7 (28.57%)	1/13 (7.69%)	12/87 (13.79%)
Musculoskeletal chest pain * 1	3/7 (42.86%)	2/7 (28.57%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Pain in extremity * 1	1/7 (14.29%)	2/7 (28.57%)	1/13 (7.69%)	1/7 (14.29%)	1/13 (7.69%)	0/87 (0.00%)
Musculoskeletal pain * 1	1/7 (14.29%)	2/7 (28.57%)	2/13 (15.38%)	3/7 (42.86%)	0/13 (0.00%)	7/87 (8.05%)
Muscle spasms * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	1/7 (14.29%)	1/13 (7.69%)	0/87 (0.00%)
Muscular weakness * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	2/7 (28.57%)	0/13 (0.00%)	5/87 (5.75%)
Groin pain * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Joint swelling * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Muscle fatigue * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Musculoskeletal stiffness * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Myopathy * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Arthritis * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Flank pain * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Joint effusion * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Neck pain * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Nervous system disorders
Headache * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	4/13 (30.77%)	25/87 (28.74%)
Dysgeusia * 1	1/7 (14.29%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	8/87 (9.20%)
Dizziness * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	1/7 (14.29%)	1/13 (7.69%)	12/87 (13.79%)
Burning sensation * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Hypoaesthesia * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	2/13 (15.38%)	0/87 (0.00%)
Neuropathy peripheral * 1	2/7 (28.57%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	8/87 (9.20%)
Peripheral sensory neuropathy * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	5/87 (5.75%)
Amnesia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Aura * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Brain oedema * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Memory impairment * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Narcolepsy * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Paraesthesia * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Sinus headache * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Dizziness postural * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Seizure * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Tremor * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Psychiatric disorders
Insomnia * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	1/7 (14.29%)	1/13 (7.69%)	13/87 (14.94%)
Anxiety * 1	1/7 (14.29%)	1/7 (14.29%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Depression * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Panic attack * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Renal and urinary disorders
Pollakiuria * 1	1/7 (14.29%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Dysuria * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Haematuria * 1	1/7 (14.29%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Micturition urgency * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Renal cyst * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Hypertonic bladder * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	2/7 (28.57%)	4/7 (57.14%)	3/13 (23.08%)	0/7 (0.00%)	3/13 (23.08%)	19/87 (21.84%)
Dyspnoea * 1	1/7 (14.29%)	3/7 (42.86%)	2/13 (15.38%)	2/7 (28.57%)	1/13 (7.69%)	18/87 (20.69%)
Oropharyngeal pain * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Nasal congestion * 1	0/7 (0.00%)	1/7 (14.29%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Dysphonia * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Haemoptysis * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Paranasal sinus discomfort * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Sinus congestion * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	6/87 (6.90%)
Upper respiratory tract congestion * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Upper-airway cough syndrome * 1	0/7 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Wheezing * 1	0/7 (0.00%)	0/7 (0.00%)	2/13 (15.38%)	2/7 (28.57%)	0/13 (0.00%)	6/87 (6.90%)
Dyspnoea exertional * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hypoxia * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Productive cough * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Sinus pain * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Skin and subcutaneous tissue disorders
Rash * 1	2/7 (28.57%)	2/7 (28.57%)	3/13 (23.08%)	0/7 (0.00%)	1/13 (7.69%)	8/87 (9.20%)
Photosensitivity reaction * 1	1/7 (14.29%)	1/7 (14.29%)	2/13 (15.38%)	1/7 (14.29%)	1/13 (7.69%)	10/87 (11.49%)
Pruritus * 1	1/7 (14.29%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Rash macular * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Alopecia * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Dermatitis acneiform * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
Dermatitis allergic * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Dry skin * 1	1/7 (14.29%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Night sweats * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Rash maculo-papular * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	7/87 (8.05%)
Social circumstances
Tanning * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Vascular disorders
Flushing * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	1/7 (14.29%)	0/13 (0.00%)	0/87 (0.00%)
Haematoma * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Hot flush * 1	0/7 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/7 (0.00%)	0/13 (0.00%)	0/87 (0.00%)
Thrombophlebitis * 1	0/7 (0.00%)	0/7 (0.00%)	0/13 (0.00%)	0/7 (0.00%)	1/13 (7.69%)	0/87 (0.00%)
1 Term from vocabulary, MedDRA Version 20.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-LaRoche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gadgeel S, Shaw AT, Barlesi F, Crino L, Yang JC, Dingemans AM, Kim DW, de Marinis F, Schulz M, Liu S, Gupta R, Smoljanovic V, Ou SI. Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies. Lung Cancer (Auckl). 2019 Nov 13;10:125-130. doi: 10.2147/LCTT.S209231. eCollection 2019.

Ou SI, Gadgeel SM, Barlesi F, Yang JC, De Petris L, Kim DW, Govindan R, Dingemans AM, Crino L, Lena H, Popat S, Ahn JS, Dansin E, Mitry E, Muller B, Bordogna W, Balas B, Morcos PN, Shaw AT. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020 Jan;139:22-27. doi: 10.1016/j.lungcan.2019.10.015. Epub 2019 Oct 14.

Morcos PN, Nueesch E, Jaminion F, Guerini E, Hsu JC, Bordogna W, Balas B, Mercier F. Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer. Cancer Chemother Pharmacol. 2018 Jul;82(1):129-138. doi: 10.1007/s00280-018-3597-5. Epub 2018 May 10.

Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, De Petris L, Kim DW, Chiappori A, Moro-Sibilot DL, Duruisseaux M, Crino L, De Pas T, Dansin E, Tessmer A, Yang JC, Han JY, Bordogna W, Golding S, Zeaiter A, Ou SI. Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Dec;34(34):4079-4085. doi: 10.1200/JCO.2016.68.4639. Epub 2016 Oct 31. Erratum In: J Clin Oncol. 2017 May 10;35(14):1631.

Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.

Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SI; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-242. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19. Erratum In: Lancet Oncol. 2017 Mar;18(3):e134.

Gadgeel SM, Gandhi L, Riely GJ, Chiappori AA, West HL, Azada MC, Morcos PN, Lee RM, Garcia L, Yu L, Boisserie F, Di Laurenzio L, Golding S, Sato J, Yokoyama S, Tanaka T, Ou SH. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014 Sep;15(10):1119-28. doi: 10.1016/S1470-2045(14)70362-6. Epub 2014 Aug 18.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01871805
• Obsolete Identifiers: NCT01588028
• Other Study ID Numbers: NP28761
• First Submitted: May 28, 2013
• First Posted: June 7, 2013
• Results First Submitted: January 14, 2016
• Results First Posted: February 12, 2016
• Last Update Posted: August 21, 2018