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Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers

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ClinicalTrials.gov Identifier: NCT02034110
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : August 21, 2023
Last Update Posted : August 21, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cancer
Interventions Drug: Dabrafenib
Drug: Trametinib
Enrollment 206
Recruitment Details The study was conducted in 41 centers in 14 countries worldwide.
Pre-assignment Details Subjects were enrolled into cohorts based on the type of histology. For each histology, up to 25 patients were planned to be enrolled. A cohort could be closed or stopped early (prior to capping at 25 patients) for futility or efficacy. An uncapped expansion cohort was planned when a particular cohort was stopped early for efficacy.
Arm/Group Title Anaplastic Thyroid Cancer (ATC) Biliary Tract Cancer (BTC) Gastrointestinal Stromal Tumor (GIST) Low Grade (WHO G1/G2) Glioma (LGG) High Grade (WHO G3/G4) Glioma (HGG) Adenocarcinoma of the Small Intestine (ASI) Hairy Cell Leukemia (HCL) Multiple Myeloma (MM)
Hide Arm/Group Description All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Period Title: Overall Study
Started [1] 36 43 1 13 45 3 55 10
Primary Analysis Cohort 15 18 1 13 24 3 24 10
Expansion Cohort 21 25 0 0 21 0 31 0
Completed 24 34 1 4 28 3 8 9
Not Completed 12 9 0 9 17 0 47 1
Reason Not Completed
Physician Decision             0             0             0             0             2             0             1             0
Lost to Follow-up             1             0             0             0             1             0             1             0
Withdrawal by Subject             5             7             0             3             7             0             3             1
Study closed by sponsor             6             2             0             6             7             0             42             0
[1]
All enrolled participants were included in the Intent-to-treat (ITT), All-treated subjects (ATS) and ITT/Evaluable populations
Arm/Group Title Anaplastic Thyroid Cancer (ATC) Biliary Tract Cancer (BTC) Gastrointestinal Stromal Tumor (GIST) Low Grade (WHO G1/G2) Glioma (LGG) High Grade (WHO G3/G4) Glioma (HGG) Adenocarcinoma of the Small Intestine (ASI) Hairy Cell Leukemia (HCL) Multiple Myeloma (MM) Total
Hide Arm/Group Description All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. Total of all reporting groups
Overall Number of Baseline Participants 36 43 1 13 45 3 55 10 206
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 43 participants 1 participants 13 participants 45 participants 3 participants 55 participants 10 participants 206 participants
69.6  (9.53) 57.0  (11.88) 77.0 [1]   (NA) 33.1  (11.51) 41.9  (14.70) 58.3  (3.21) 64.8  (10.77) 66.9  (6.89) 57.1  (16.40)
[1]
Only one participant analyzed
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 43 participants 1 participants 13 participants 45 participants 3 participants 55 participants 10 participants 206 participants
Female
20
  55.6%
24
  55.8%
1
 100.0%
9
  69.2%
22
  48.9%
1
  33.3%
8
  14.5%
5
  50.0%
90
  43.7%
Male
16
  44.4%
19
  44.2%
0
   0.0%
4
  30.8%
23
  51.1%
2
  66.7%
47
  85.5%
5
  50.0%
116
  56.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 36 participants 43 participants 1 participants 13 participants 45 participants 3 participants 55 participants 10 participants 206 participants
African American/African Heritage 0 0 0 0 2 1 0 1 4
American Indian or Alaska Native 0 0 0 0 1 0 0 0 1
Asian - Central/South Asian Heritage 1 0 0 0 0 0 0 0 1
Asian - East Asian Heritage 11 1 0 0 4 0 0 1 17
Asian - Japanese Heritage 2 2 0 2 1 0 0 0 7
Asian - South East Asian Heritage 2 0 0 1 1 0 0 0 4
White - Arabic/North African Heritage 1 1 0 0 2 0 1 0 5
White - White/Caucasian/European heritage 17 39 1 10 32 2 48 8 157
Missing 2 0 0 0 2 0 6 0 10
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 43 participants 1 participants 13 participants 45 participants 3 participants 55 participants 10 participants 206 participants
Grade 0
4
  11.1%
17
  39.5%
1
 100.0%
5
  38.5%
14
  31.1%
3
 100.0%
25
  45.5%
3
  30.0%
72
  35.0%
Grade 1
30
  83.3%
24
  55.8%
0
   0.0%
7
  53.8%
24
  53.3%
0
   0.0%
27
  49.1%
6
  60.0%
118
  57.3%
Grade 2
2
   5.6%
2
   4.7%
0
   0.0%
1
   7.7%
7
  15.6%
0
   0.0%
3
   5.5%
1
  10.0%
16
   7.8%
[1]
Measure Description: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classifies participants according to their functional impairment, with scores ranging from 0 (fully active) to 5 (dead). ECOG PS: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours
1.Primary Outcome
Title Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Anaplastic Thyroid Cancer (ATC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ up to 78 months
56
(38.1 to 72.1)
Investigator assessment @ up to 92 months
56
(38.1 to 72.1)
Independent radiology review @ up to 78 months
53
(35.5 to 69.6)
Independent radiology review @ up to 92 months
53
(35.5 to 69.6)
2.Primary Outcome
Title Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Biliary Tract Cancer (BTC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ up to 78 months
53
(37.7 to 68.8)
Investigator assessment @ up to 92 months
53
(37.7 to 68.8)
Independent radiology review @ up to 78 months
47
(31.2 to 62.3)
Independent radiology review @ up to 92 months
47
(31.2 to 62.3)
3.Primary Outcome
Title Overall Response Rate (ORR) in the Gastrointestinal Stromal Tumor (GIST) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Gastrointestinal Stromal Tumor (GIST)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ 78 months
0 [1] 
(NA to NA)
Investigator assessment @ 92 months
0 [1] 
(NA to NA)
[1]
95% Confidence Interval not determined as there are an insufficient number of participants with events.
4.Primary Outcome
Title Overall Response Rate (ORR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Adenocarcinoma of the Small Intestine (ASI)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 3
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ up to 78 months
67
(9.4 to 99.2)
Investigator assessment @ up to 92 months
67
(9.4 to 99.2)
5.Primary Outcome
Title Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (response assessment criteria (CR, PR, and minor response [MR]) WHO Grade 1 and 2 Glioma) by investigator assessment as defined by response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort
Arm/Group Title Low Grade (WHO G1/G2) Glioma (LGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment/Response rate @ up to 78 months
69
(38.6 to 90.9)
Investigator assessment/Response rate @ up to 92 months
69
(38.6 to 90.9)
Independent radiology review/Response rate @ up to 78 months
69
(38.6 to 90.9)
Independent radiology review/Response rate @ up to 92 months
62
(31.6 to 86.1)
6.Primary Outcome
Title Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (updated response assessment criteria (CR, PR) WHO Grade 3 and 4 Glioma) by investigator assessment as defined by modified response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title High Grade (WHO G3/G4) Glioma (HGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ up to 78 months
33
(20.0 to 49.0)
Investigator assessment @ up to 92 months
33
(20.0 to 49.0)
Independent radiology review @ up to 78 months
31
(18.2 to 46.6)
Independent radiology review @ up to 92 months
31
(18.2 to 46.6)
7.Primary Outcome
Title Overall Response Rate (ORR) in the Hairy Cell Leukemia (HCL) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with CR +/- minimal residual disease [MRD], PR by investigator assessment as defined by the Consensus Resolution Criteria adapted from the National Comprehensive Cancer Network (NCCN) guidelines. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Hairy Cell Leukemia (HCL)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 55
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ up to 78 months
89
(77.8 to 95.9)
Investigator assessment @ up to 92 months
89
(77.8 to 95.9)
8.Primary Outcome
Title Overall Response Rate (ORR) in the Multiple Myeloma (MM) Cohort
Hide Description Overall Response Rate (ORR) was defined as the percentage of participants with stringent complete response (sCR), CR, PR, very good partial response (VGPR) by investigator assessment as defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time Frame From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort
Arm/Group Title Multiple Myeloma (MM)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Investigator assessment @ up to 78 months
50
(18.7 to 81.3)
Investigator assessment @ up to 92 months
50
(18.7 to 81.3)
9.Secondary Outcome
Title Duration of Response (DoR) in the Anaplastic Thyroid Cancer (ATC) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
Arm/Group Title Anaplastic Thyroid Cancer (ATC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
62.4 [1] 
(32.1 to NA)
Independent radiology review
59.1
(16.6 to 171.4)
[1]
Not estimable due to insufficient events observed.
10.Secondary Outcome
Title Duration of Response (DoR) in the Biliary Tract Cancer (BTC) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
Arm/Group Title Biliary Tract Cancer (BTC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 23
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
38.9
(24.3 to 59.4)
Independent radiology review
45.4
(20.1 to 64.9)
11.Secondary Outcome
Title Duration of Response (DoR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort. Only responders were included in the analysis.
Arm/Group Title Adenocarcinoma of the Small Intestine (ASI)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 2
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
33.4 [1] 
(NA to NA)
Independent radiology review
32.8 [1] 
(32.1 to NA)
[1]
Not estimable due to insufficient events observed.
12.Secondary Outcome
Title Duration of Response (DoR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort. Only responders were included in the analysis.
Arm/Group Title Low Grade (WHO G1/G2) Glioma (LGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 9
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
NA [1] 
(24.1 to NA)
Independent radiology review
84.3 [1] 
(16.4 to NA)
[1]
Not estimable due to insufficient events observed
13.Secondary Outcome
Title Duration of Response (DoR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
Arm/Group Title High Grade (WHO G3/G4) Glioma (HGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
135.7
(32.0 to 192.0)
Independent radiology review
59.3
(20.1 to 116.0)
14.Secondary Outcome
Title Duration of Response (DoR) in the Hairy Cell Leukemia (HCL) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
Arm/Group Title Hairy Cell Leukemia (HCL)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 49
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(NA to NA)
[1]
Not estimable due to insufficient events observed
15.Secondary Outcome
Title Duration of Response (DoR) in the Multiple Myeloma (MM) Cohort
Hide Description For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time Frame From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort. Only responders were included in the analysis.
Arm/Group Title Multiple Myeloma (MM)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 5
Median (95% Confidence Interval)
Unit of Measure: Weeks
48.1 [1] 
(24.3 to NA)
[1]
Not estimable due to insufficient events observed
16.Secondary Outcome
Title Progression Free Survival (PFS) in the Anaplastic Thyroid Cancer (ATC) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Anaplastic Thyroid Cancer (ATC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
29.1
(20.3 to 59.9)
Independent radiology review
24.1
(16.1 to 56.0)
17.Secondary Outcome
Title Progression Free Survival (PFS) in the Biliary Tract Cancer (BTC) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Biliary Tract Cancer (BTC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 43
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
39.0
(24.1 to 41.0)
Independent radiology review
32.6
(23.6 to 56.0)
18.Secondary Outcome
Title Progression Free Survival (PFS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort.
Arm/Group Title Adenocarcinoma of the Small Intestine (ASI)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 3
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
41.3 [1] 
(NA to NA)
Independent radiology review
40.1 [1] 
(4.1 to NA)
[1]
Not estimable due to insufficient events observed
19.Secondary Outcome
Title Progression Free Survival (PFS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort.
Arm/Group Title Low Grade (WHO G1/G2) Glioma (LGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
NA [1] 
(32.1 to NA)
Independent radiology review
40.1
(20.3 to 143.7)
[1]
Not estimable due to insufficient events observed
20.Secondary Outcome
Title Progression Free Survival (PFS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title High Grade (WHO G3/G4) Glioma (HGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 45
Median (95% Confidence Interval)
Unit of Measure: Weeks
Investigator assessment
24.0
(8.0 to 59.4)
Independent radiology review
19.7
(8.0 to 32.1)
21.Secondary Outcome
Title Progression Free Survival (PFS) in the Hairy Cell Leukemia (HCL) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Hairy Cell Leukemia (HCL)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 55
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(NA to NA)
[1]
Not estimable due to insufficient events observed
22.Secondary Outcome
Title Progression Free Survival (PFS) in the Multiple Myeloma (MM) Cohort
Hide Description Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time Frame From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - primary analysis cohort
Arm/Group Title Multiple Myeloma (MM)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: Weeks
27.5
(10.0 to 55.9)
23.Secondary Outcome
Title Overall Survival (OS) in the Anaplastic Thyroid Cancer (ATC) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Anaplastic Thyroid Cancer (ATC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 36
Median (95% Confidence Interval)
Unit of Measure: Weeks
62.9
(29.6 to 100.9)
24.Secondary Outcome
Title Overall Survival (OS) in the Biliary Tract Cancer (BTC) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Biliary Tract Cancer (BTC)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 43
Median (95% Confidence Interval)
Unit of Measure: Weeks
58.9
(45.4 to 76.6)
25.Secondary Outcome
Title Overall Survival (OS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort
Arm/Group Title Adenocarcinoma of the Small Intestine (ASI)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 3
Median (95% Confidence Interval)
Unit of Measure: Weeks
94.6 [1] 
(14.9 to NA)
[1]
Not estimable due to insufficient events observed
26.Secondary Outcome
Title Overall Survival (OS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort
Arm/Group Title Low Grade (WHO G1/G2) Glioma (LGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(50.4 to NA)
[1]
Not estimable due to insufficient events observed
27.Secondary Outcome
Title Overall Survival (OS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined.
Arm/Group Title High Grade (WHO G3/G4) Glioma (HGG)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 45
Median (95% Confidence Interval)
Unit of Measure: Weeks
76.4
(41.1 to 139.9)
28.Secondary Outcome
Title Overall Survival (OS) in the Hairy Cell Leukemia (HCL) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary and expansion cohort combined
Arm/Group Title Hairy Cell Leukemia (HCL)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 55
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(NA to NA)
[1]
Not estimable due to insufficient events observed
29.Secondary Outcome
Title Overall Survival (OS) in the Multiple Myeloma (MM) Cohort
Hide Description Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time Frame From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT/Evaluable population - Primary analysis cohort
Arm/Group Title Multiple Myeloma (MM)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: Weeks
147.3
(12.4 to 194.0)
30.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) through the monitoring of relevant clinical and laboratory safety parameters.
Time Frame From study treatment start date till 30 days safety follow-up, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Subjects (ATS) population - Primary and expansion cohort combined
Arm/Group Title Anaplastic Thyroid Cancer (ATC) Biliary Tract Cancer (BTC) Gastrointestinal Stromal Tumor (GIST) Low Grade (WHO G1/G2) Glioma (LGG) High Grade (WHO G3/G4) Glioma (HGG) Adenocarcinoma of the Small Intestine (ASI) Hairy Cell Leukemia (HCL) Multiple Myeloma (MM)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 36 43 1 13 45 3 55 10
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
36
 100.0%
43
 100.0%
1
 100.0%
12
  92.3%
42
  93.3%
3
 100.0%
55
 100.0%
9
  90.0%
AEs related to study treatment
27
  75.0%
42
  97.7%
1
 100.0%
12
  92.3%
37
  82.2%
3
 100.0%
52
  94.5%
7
  70.0%
AEs leading to permanent discontinuation of any study treatment
6
  16.7%
1
   2.3%
0
   0.0%
2
  15.4%
4
   8.9%
1
  33.3%
13
  23.6%
1
  10.0%
AEs leading to dose reduction
17
  47.2%
15
  34.9%
1
 100.0%
4
  30.8%
18
  40.0%
2
  66.7%
29
  52.7%
5
  50.0%
AEs leading to dose interruption/delay
19
  52.8%
24
  55.8%
1
 100.0%
6
  46.2%
18
  40.0%
2
  66.7%
40
  72.7%
6
  60.0%
Any SAE
20
  55.6%
17
  39.5%
1
 100.0%
3
  23.1%
16
  35.6%
0
   0.0%
32
  58.2%
4
  40.0%
SAEs related to study treatment
7
  19.4%
9
  20.9%
0
   0.0%
1
   7.7%
7
  15.6%
0
   0.0%
19
  34.5%
3
  30.0%
Fatal SAEs
3
   8.3%
2
   4.7%
0
   0.0%
0
   0.0%
1
   2.2%
0
   0.0%
3
   5.5%
0
   0.0%
31.Post-Hoc Outcome
Title All Collected Deaths
Hide Description On-treatment deaths were collected from first dose of study medication to 30 days after study drug discontinuation, for a maximum duration of 85 months. Post-treatment survival follow-up deaths were collected from day 31 after last dose of first dose of study medication, up to 92 months. All deaths refer to the sum of on-treatment deaths and post-treatment survival follow-up deaths.
Time Frame On-treatment deaths: Up to 85 months. Post-treatment survival follow-up deaths: Up to 92 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All-treated Subjects (ATS) population - Primary and expansion cohort combined
Arm/Group Title Anaplastic Thyroid Cancer (ATC) Biliary Tract Cancer (BTC) Gastrointestinal Stromal Tumor (GIST) Low Grade (WHO G1/G2) Glioma (LGG) High Grade (WHO G3/G4) Glioma (HGG) Adenocarcinoma of the Small Intestine (ASI) Hairy Cell Leukemia (HCL) Multiple Myeloma (MM)
Hide Arm/Group Description:
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death.
Overall Number of Participants Analyzed 36 43 1 13 45 3 55 10
Measure Type: Number
Unit of Measure: Participants
On-treatment deaths Number Analyzed 36 participants 43 participants 1 participants 13 participants 45 participants 3 participants 55 participants 10 participants
6 6 0 1 2 0 4 1
Post-treatment survival follow-up deaths Number Analyzed 30 participants 37 participants 1 participants 12 participants 43 participants 3 participants 51 participants 9 participants
18 28 1 3 26 3 4 8
All deaths Number Analyzed 36 participants 43 participants 1 participants 13 participants 45 participants 3 participants 55 participants 10 participants
24 34 1 4 28 3 8 9
Time Frame Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to a maximum duration of approximately 85 months. Deaths were collected in the post treatment survival follow up period from 31 days after last dose of study medication until the end of the study, up to approximately 92 months. These are not considered Adverse Events.
Adverse Event Reporting Description

Any sign or symptom that occurred during the conduct of the trial and safety follow-up.

Deaths in the post treatment survival follow-up period are not considered Adverse Events. The total number at risk in the post treatment survival follow-up period includes patients that entered the post treatment survival follow-up period.
 
Arm/Group Title Anaplastic Thyroid Cancer (ATC) (On-Treatment) Biliary Tract Cancer (BTC) (On-Treatment) Gastrointestinal Stromal Tumor (GIST) (On-Treatment) Low Grade (WHO G1/G2) Glioma (LGG) (On-Treatment) High Grade (WHO G3/G4) Glioma (HGG) (On-Treatment) Adenocarcinoma of the Small Intestine (ASI) (On-Treatment) Hairy Cell Leukemia (HCL) (On-Treatment) Multiple Myeloma (MM) (On-Treatment) Anaplastic Thyroid Cancer (ATC) (Post-treatment Survival Follow-up) Biliary Tract Cancer (BTC) (Post-treatment Survival Follow-up) Gastrointestinal Stromal Tumor (GIST) (Post-treatment Survival Follow-up) Low Grade (WHO G1/G2) Glioma (LGG) (Post-treatment Survival Follow-up) High Grade (WHO G3/G4) Glioma (HGG) (Post-treatment Survival Follow-up) Adenocarcinoma of the Small Intestine (ASI) (Post-treatment Survival Follow-up) Hairy Cell Leukemia (HCL) (Post-treatment Survival Follow-up) Multiple Myeloma (MM) (Post-treatment Survival Follow-up)
Hide Arm/Group Description All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period. Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period.
All-Cause Mortality
Anaplastic Thyroid Cancer (ATC) (On-Treatment) Biliary Tract Cancer (BTC) (On-Treatment) Gastrointestinal Stromal Tumor (GIST) (On-Treatment) Low Grade (WHO G1/G2) Glioma (LGG) (On-Treatment) High Grade (WHO G3/G4) Glioma (HGG) (On-Treatment) Adenocarcinoma of the Small Intestine (ASI) (On-Treatment) Hairy Cell Leukemia (HCL) (On-Treatment) Multiple Myeloma (MM) (On-Treatment) Anaplastic Thyroid Cancer (ATC) (Post-treatment Survival Follow-up) Biliary Tract Cancer (BTC) (Post-treatment Survival Follow-up) Gastrointestinal Stromal Tumor (GIST) (Post-treatment Survival Follow-up) Low Grade (WHO G1/G2) Glioma (LGG) (Post-treatment Survival Follow-up) High Grade (WHO G3/G4) Glioma (HGG) (Post-treatment Survival Follow-up) Adenocarcinoma of the Small Intestine (ASI) (Post-treatment Survival Follow-up) Hairy Cell Leukemia (HCL) (Post-treatment Survival Follow-up) Multiple Myeloma (MM) (Post-treatment Survival Follow-up)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/36 (16.67%)   6/43 (13.95%)   0/1 (0.00%)   1/13 (7.69%)   2/45 (4.44%)   0/3 (0.00%)   4/55 (7.27%)   1/10 (10.00%)   18/30 (60.00%)   28/37 (75.68%)   1/1 (100.00%)   3/12 (25.00%)   26/43 (60.47%)   3/3 (100.00%)   4/51 (7.84%)   8/9 (88.89%) 
Hide Serious Adverse Events
Anaplastic Thyroid Cancer (ATC) (On-Treatment) Biliary Tract Cancer (BTC) (On-Treatment) Gastrointestinal Stromal Tumor (GIST) (On-Treatment) Low Grade (WHO G1/G2) Glioma (LGG) (On-Treatment) High Grade (WHO G3/G4) Glioma (HGG) (On-Treatment) Adenocarcinoma of the Small Intestine (ASI) (On-Treatment) Hairy Cell Leukemia (HCL) (On-Treatment) Multiple Myeloma (MM) (On-Treatment) Anaplastic Thyroid Cancer (ATC) (Post-treatment Survival Follow-up) Biliary Tract Cancer (BTC) (Post-treatment Survival Follow-up) Gastrointestinal Stromal Tumor (GIST) (Post-treatment Survival Follow-up) Low Grade (WHO G1/G2) Glioma (LGG) (Post-treatment Survival Follow-up) High Grade (WHO G3/G4) Glioma (HGG) (Post-treatment Survival Follow-up) Adenocarcinoma of the Small Intestine (ASI) (Post-treatment Survival Follow-up) Hairy Cell Leukemia (HCL) (Post-treatment Survival Follow-up) Multiple Myeloma (MM) (Post-treatment Survival Follow-up)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/36 (55.56%)   17/43 (39.53%)   1/1 (100.00%)   3/13 (23.08%)   16/45 (35.56%)   0/3 (0.00%)   32/55 (58.18%)   4/10 (40.00%)   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0 
Blood and lymphatic system disorders                                 
Anaemia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Autoimmune haemolytic anaemia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Febrile neutropenia † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haemolytic uraemic syndrome † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Leukopenia † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neutropenia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac disorders                                 
Atrial fibrillation † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Atrioventricular block † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac ventricular thrombosis † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Conduction disorder † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Myocardial infarction † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Myocardial ischaemia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Myocarditis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Stress cardiomyopathy † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Ear and labyrinth disorders                                 
Vertigo † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Endocrine disorders                                 
Adrenocortical insufficiency acute † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Eye disorders                                 
Amaurosis fugax † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Diplopia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Retinal detachment † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrointestinal disorders                                 
Abdominal pain † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Constipation † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Diarrhoea † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphagia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haematochezia † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Intestinal obstruction † 1  0/36 (0.00%)  0/43 (0.00%)  1/1 (100.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Large intestinal haemorrhage † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nausea † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  3/45 (6.67%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oesophageal stenosis † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rectal haemorrhage † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Small intestinal obstruction † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vomiting † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  3/45 (6.67%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
General disorders                                 
Chills † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fat necrosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fatigue † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
General physical health deterioration † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pyrexia † 1  1/36 (2.78%)  9/43 (20.93%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  10/55 (18.18%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatobiliary disorders                                 
Cholangitis † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatic cytolysis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatotoxicity † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Immune system disorders                                 
Haemophagocytic lymphohistiocytosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Infections and infestations                                 
Bacteraemia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bacterial diarrhoea † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cellulitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cervicitis human papilloma virus † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Clostridium difficile infection † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Device related infection † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Diverticulitis † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Enterobacter infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gastroenteritis pseudomonas † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Influenza † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lymph node tuberculosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Otitis media acute † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Parotitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pelvic infection † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia † 1  8/36 (22.22%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia aspiration † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia necrotising † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary sepsis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pyelonephritis acute † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory tract infection † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Sepsis † 1  1/36 (2.78%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Staphylococcal infection † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Upper respiratory tract infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary tract infection † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary tract infection bacterial † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Viral infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Wound infection † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Injury, poisoning and procedural complications                                 
Clavicle fracture † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Contusion † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fall † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Femoral neck fracture † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Post procedural discomfort † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rib fracture † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Investigations                                 
Ejection fraction decreased † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neutrophil count decreased † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Transaminases increased † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
White blood cell count decreased † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Metabolism and nutrition disorders                                 
Dehydration † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperglycaemia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperglycaemic hyperosmolar nonketotic syndrome † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyponatraemia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal and connective tissue disorders                                 
Muscle spasms † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Muscular weakness † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal chest pain † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neck pain † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rhabdomyolysis † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Spinal pain † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                 
Adenocarcinoma of the cervix † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Adenocarcinoma pancreas † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Basal cell carcinoma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bladder neoplasm † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bladder transitional cell carcinoma † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bowen's disease † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Chronic lymphocytic leukaemia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrointestinal stromal tumour † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hodgkin's disease † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Invasive breast carcinoma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Metastases to bone † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Metastatic squamous cell carcinoma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Prostate cancer † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Squamous cell carcinoma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Squamous cell carcinoma of skin † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nervous system disorders                                 
Amnesia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Aphasia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Ataxia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Brain oedema † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Central nervous system lesion † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cerebral cyst † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cerebral thrombosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dizziness † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Epilepsy † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Facial nerve disorder † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Guillain-Barre syndrome † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haemorrhagic stroke † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Headache † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hydrocephalus † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Paralysis recurrent laryngeal nerve † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Seizure † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  4/45 (8.89%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Syncope † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Product Issues                                 
Device failure † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Psychiatric disorders                                 
Hallucination † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Renal and urinary disorders                                 
Acute kidney injury † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Calculus urinary † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haematuria † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Renal colic † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary retention † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory, thoracic and mediastinal disorders                                 
Aspiration † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspnoea † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pleural effusion † 1  3/36 (8.33%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumothorax † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary embolism † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary granuloma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary haematoma † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin and subcutaneous tissue disorders                                 
Erythema nodosum † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin ulcer † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vascular disorders                                 
Aortic thrombosis † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypotension † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Thrombophlebitis † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
1
Term from vocabulary, MedDRA (24.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Anaplastic Thyroid Cancer (ATC) (On-Treatment) Biliary Tract Cancer (BTC) (On-Treatment) Gastrointestinal Stromal Tumor (GIST) (On-Treatment) Low Grade (WHO G1/G2) Glioma (LGG) (On-Treatment) High Grade (WHO G3/G4) Glioma (HGG) (On-Treatment) Adenocarcinoma of the Small Intestine (ASI) (On-Treatment) Hairy Cell Leukemia (HCL) (On-Treatment) Multiple Myeloma (MM) (On-Treatment) Anaplastic Thyroid Cancer (ATC) (Post-treatment Survival Follow-up) Biliary Tract Cancer (BTC) (Post-treatment Survival Follow-up) Gastrointestinal Stromal Tumor (GIST) (Post-treatment Survival Follow-up) Low Grade (WHO G1/G2) Glioma (LGG) (Post-treatment Survival Follow-up) High Grade (WHO G3/G4) Glioma (HGG) (Post-treatment Survival Follow-up) Adenocarcinoma of the Small Intestine (ASI) (Post-treatment Survival Follow-up) Hairy Cell Leukemia (HCL) (Post-treatment Survival Follow-up) Multiple Myeloma (MM) (Post-treatment Survival Follow-up)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   36/36 (100.00%)   43/43 (100.00%)   1/1 (100.00%)   12/13 (92.31%)   42/45 (93.33%)   3/3 (100.00%)   55/55 (100.00%)   9/10 (90.00%)   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0 
Blood and lymphatic system disorders                                 
Anaemia † 1  12/36 (33.33%)  10/43 (23.26%)  0/1 (0.00%)  4/13 (30.77%)  9/45 (20.00%)  0/3 (0.00%)  10/55 (18.18%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Leukopenia † 1  2/36 (5.56%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  4/45 (8.89%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lymphopenia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Microcytic anaemia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neutropenia † 1  2/36 (5.56%)  3/43 (6.98%)  0/1 (0.00%)  1/13 (7.69%)  7/45 (15.56%)  1/3 (33.33%)  6/55 (10.91%)  4/10 (40.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Thrombocytopenia † 1  2/36 (5.56%)  7/43 (16.28%)  0/1 (0.00%)  1/13 (7.69%)  4/45 (8.89%)  0/3 (0.00%)  3/55 (5.45%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac disorders                                 
Atrial fibrillation † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  7/55 (12.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Atrioventricular block first degree † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bradycardia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Sinus bradycardia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  13/55 (23.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Tachycardia † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Ear and labyrinth disorders                                 
Ear pain † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  7/55 (12.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoacusis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Tinnitus † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vertigo † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  3/13 (23.08%)  2/45 (4.44%)  0/3 (0.00%)  6/55 (10.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Endocrine disorders                                 
Hypothyroidism † 1  4/36 (11.11%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Eye disorders                                 
Cataract † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Diplopia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dry eye † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  5/55 (9.09%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Eye pain † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Eyelid oedema † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Iritis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lacrimation increased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Macular oedema † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Papilloedema † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Photophobia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  3/45 (6.67%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Saccadic eye movement † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Uveitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vision blurred † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  2/13 (15.38%)  5/45 (11.11%)  0/3 (0.00%)  14/55 (25.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Visual impairment † 1  4/36 (11.11%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vitreous floaters † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  7/55 (12.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrointestinal disorders                                 
Abdominal discomfort † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal distension † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal pain † 1  2/36 (5.56%)  5/43 (11.63%)  0/1 (0.00%)  2/13 (15.38%)  2/45 (4.44%)  2/3 (66.67%)  12/55 (21.82%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal pain lower † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal pain upper † 1  2/36 (5.56%)  7/43 (16.28%)  0/1 (0.00%)  2/13 (15.38%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Constipation † 1  8/36 (22.22%)  9/43 (20.93%)  1/1 (100.00%)  4/13 (30.77%)  8/45 (17.78%)  1/3 (33.33%)  22/55 (40.00%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Diarrhoea † 1  7/36 (19.44%)  14/43 (32.56%)  0/1 (0.00%)  4/13 (30.77%)  5/45 (11.11%)  1/3 (33.33%)  19/55 (34.55%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dry mouth † 1  5/36 (13.89%)  8/43 (18.60%)  0/1 (0.00%)  2/13 (15.38%)  3/45 (6.67%)  0/3 (0.00%)  8/55 (14.55%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspepsia † 1  1/36 (2.78%)  3/43 (6.98%)  1/1 (100.00%)  3/13 (23.08%)  1/45 (2.22%)  0/3 (0.00%)  5/55 (9.09%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphagia † 1  6/36 (16.67%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Flatulence † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrooesophageal reflux disease † 1  3/36 (8.33%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  1/3 (33.33%)  6/55 (10.91%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gingival bleeding † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haemorrhoids † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperaesthesia teeth † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nausea † 1  12/36 (33.33%)  18/43 (41.86%)  1/1 (100.00%)  7/13 (53.85%)  14/45 (31.11%)  0/3 (0.00%)  27/55 (49.09%)  5/10 (50.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Noninfective gingivitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oral pain † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Retching † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Salivary gland mass † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Stomatitis † 1  2/36 (5.56%)  3/43 (6.98%)  1/1 (100.00%)  2/13 (15.38%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Toothache † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vomiting † 1  7/36 (19.44%)  15/43 (34.88%)  1/1 (100.00%)  4/13 (30.77%)  11/45 (24.44%)  1/3 (33.33%)  13/55 (23.64%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
General disorders                                 
Asthenia † 1  3/36 (8.33%)  7/43 (16.28%)  1/1 (100.00%)  0/13 (0.00%)  4/45 (8.89%)  0/3 (0.00%)  3/55 (5.45%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Chills † 1  8/36 (22.22%)  12/43 (27.91%)  0/1 (0.00%)  3/13 (23.08%)  5/45 (11.11%)  1/3 (33.33%)  30/55 (54.55%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fatigue † 1  13/36 (36.11%)  14/43 (32.56%)  0/1 (0.00%)  8/13 (61.54%)  19/45 (42.22%)  0/3 (0.00%)  29/55 (52.73%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Feeling cold † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gait disturbance † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Influenza like illness † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  2/13 (15.38%)  1/45 (2.22%)  0/3 (0.00%)  7/55 (12.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Injection site reaction † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Malaise † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  6/55 (10.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Mucosal inflammation † 1  3/36 (8.33%)  3/43 (6.98%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nodule † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Non-cardiac chest pain † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  3/13 (23.08%)  1/45 (2.22%)  1/3 (33.33%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oedema † 1  1/36 (2.78%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oedema peripheral † 1  5/36 (13.89%)  4/43 (9.30%)  0/1 (0.00%)  2/13 (15.38%)  3/45 (6.67%)  1/3 (33.33%)  27/55 (49.09%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pain † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  1/3 (33.33%)  1/55 (1.82%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Peripheral swelling † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pyrexia † 1  17/36 (47.22%)  25/43 (58.14%)  1/1 (100.00%)  8/13 (61.54%)  11/45 (24.44%)  2/3 (66.67%)  41/55 (74.55%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Thirst † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Xerosis † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Immune system disorders                                 
Hypersensitivity † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Sarcoidosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Infections and infestations                                 
Abdominal abscess † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Abscess limb † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bronchitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  5/55 (9.09%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
COVID-19 † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Conjunctivitis † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  8/55 (14.55%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Folliculitis † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  3/45 (6.67%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fungal infection † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gastroenteritis † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gingivitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Herpes zoster † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nasopharyngitis † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  5/13 (38.46%)  7/45 (15.56%)  0/3 (0.00%)  4/55 (7.27%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Onychomycosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oral candidiasis † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  1/3 (33.33%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oral herpes † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oropharyngeal candidiasis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Paronychia † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  3/45 (6.67%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pharyngitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  6/55 (10.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rash pustular † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rhinitis † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  5/55 (9.09%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Sinusitis † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  4/55 (7.27%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin candida † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Streptococcal infection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Subcutaneous abscess † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Tooth abscess † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Tooth infection † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  8/55 (14.55%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Upper respiratory tract infection † 1  3/36 (8.33%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  15/55 (27.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary tract infection † 1  2/36 (5.56%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  6/45 (13.33%)  1/3 (33.33%)  8/55 (14.55%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Injury, poisoning and procedural complications                                 
Contusion † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  10/55 (18.18%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fall † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  9/55 (16.36%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Procedural pain † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  1/3 (33.33%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Radiation associated pain † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin laceration † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Thermal burn † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Investigations                                 
Alanine aminotransferase increased † 1  4/36 (11.11%)  7/43 (16.28%)  0/1 (0.00%)  3/13 (23.08%)  9/45 (20.00%)  0/3 (0.00%)  18/55 (32.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Aspartate aminotransferase increased † 1  5/36 (13.89%)  11/43 (25.58%)  0/1 (0.00%)  4/13 (30.77%)  9/45 (20.00%)  0/3 (0.00%)  21/55 (38.18%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood alkaline phosphatase increased † 1  6/36 (16.67%)  9/43 (20.93%)  0/1 (0.00%)  3/13 (23.08%)  0/45 (0.00%)  0/3 (0.00%)  16/55 (29.09%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood bilirubin increased † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood creatine phosphokinase increased † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood creatinine increased † 1  2/36 (5.56%)  5/43 (11.63%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  13/55 (23.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood glucose increased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood lactate dehydrogenase increased † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  4/55 (7.27%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood oestrogen decreased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood testosterone decreased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood urea increased † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Blood uric acid increased † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
C-reactive protein increased † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Ejection fraction decreased † 1  3/36 (8.33%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  5/45 (11.11%)  0/3 (0.00%)  7/55 (12.73%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Electrocardiogram QT prolonged † 1  3/36 (8.33%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  5/55 (9.09%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Gamma-glutamyltransferase increased † 1  3/36 (8.33%)  12/43 (27.91%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Glycosylated haemoglobin increased † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lipase increased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Liver function test increased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lymphocyte count decreased † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neutrophil count decreased † 1  3/36 (8.33%)  4/43 (9.30%)  0/1 (0.00%)  3/13 (23.08%)  8/45 (17.78%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neutrophil count increased † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Platelet count decreased † 1  1/36 (2.78%)  5/43 (11.63%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Urine output decreased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Weight decreased † 1  4/36 (11.11%)  3/43 (6.98%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  1/3 (33.33%)  3/55 (5.45%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Weight increased † 1  1/36 (2.78%)  4/43 (9.30%)  0/1 (0.00%)  3/13 (23.08%)  1/45 (2.22%)  1/3 (33.33%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
White blood cell count decreased † 1  5/36 (13.89%)  10/43 (23.26%)  0/1 (0.00%)  3/13 (23.08%)  6/45 (13.33%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Metabolism and nutrition disorders                                 
Cachexia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Decreased appetite † 1  12/36 (33.33%)  10/43 (23.26%)  0/1 (0.00%)  2/13 (15.38%)  6/45 (13.33%)  0/3 (0.00%)  7/55 (12.73%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dehydration † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Diabetes mellitus † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypercalcaemia † 1  3/36 (8.33%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperglycaemia † 1  5/36 (13.89%)  8/43 (18.60%)  0/1 (0.00%)  2/13 (15.38%)  4/45 (8.89%)  0/3 (0.00%)  25/55 (45.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperkalaemia † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperuricaemia † 1  2/36 (5.56%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoalbuminaemia † 1  7/36 (19.44%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  4/45 (8.89%)  0/3 (0.00%)  6/55 (10.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypocalcaemia † 1  5/36 (13.89%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoglycaemia † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  0/13 (0.00%)  3/45 (6.67%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypokalaemia † 1  4/36 (11.11%)  4/43 (9.30%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  3/55 (5.45%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypomagnesaemia † 1  2/36 (5.56%)  5/43 (11.63%)  0/1 (0.00%)  2/13 (15.38%)  4/45 (8.89%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyponatraemia † 1  7/36 (19.44%)  5/43 (11.63%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypophosphataemia † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  2/13 (15.38%)  4/45 (8.89%)  0/3 (0.00%)  11/55 (20.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal and connective tissue disorders                                 
Arthralgia † 1  5/36 (13.89%)  6/43 (13.95%)  0/1 (0.00%)  7/13 (53.85%)  7/45 (15.56%)  0/3 (0.00%)  21/55 (38.18%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Arthritis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  5/55 (9.09%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Back pain † 1  6/36 (16.67%)  4/43 (9.30%)  0/1 (0.00%)  3/13 (23.08%)  3/45 (6.67%)  0/3 (0.00%)  13/55 (23.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Bone pain † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Flank pain † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Foot deformity † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Joint range of motion decreased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Joint stiffness † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Joint swelling † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Muscle spasms † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  2/13 (15.38%)  5/45 (11.11%)  0/3 (0.00%)  6/55 (10.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Muscle twitching † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Muscular weakness † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  4/45 (8.89%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal chest pain † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal pain † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Myalgia † 1  2/36 (5.56%)  8/43 (18.60%)  0/1 (0.00%)  2/13 (15.38%)  7/45 (15.56%)  0/3 (0.00%)  25/55 (45.45%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Myopathy † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neck mass † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neck pain † 1  3/36 (8.33%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pain in extremity † 1  1/36 (2.78%)  3/43 (6.98%)  0/1 (0.00%)  2/13 (15.38%)  4/45 (8.89%)  0/3 (0.00%)  19/55 (34.55%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pain in jaw † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Spinal pain † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Synovial cyst † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                 
Basal cell carcinoma † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  13/55 (23.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Fibroma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lipoma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Melanocytic naevus † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Seborrhoeic keratosis † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin papilloma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nervous system disorders                                 
Aphasia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  4/45 (8.89%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Balance disorder † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dizziness † 1  7/36 (19.44%)  1/43 (2.33%)  0/1 (0.00%)  2/13 (15.38%)  5/45 (11.11%)  0/3 (0.00%)  20/55 (36.36%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dysgeusia † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  5/55 (9.09%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Epilepsy † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  3/45 (6.67%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Facial paralysis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Facial paresis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Head discomfort † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Headache † 1  8/36 (22.22%)  10/43 (23.26%)  0/1 (0.00%)  8/13 (61.54%)  18/45 (40.00%)  0/3 (0.00%)  21/55 (38.18%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hemiparesis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  3/45 (6.67%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hydrocephalus † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoaesthesia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  3/45 (6.67%)  0/3 (0.00%)  1/55 (1.82%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
IIIrd nerve disorder † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Intercostal neuralgia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Memory impairment † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  3/13 (23.08%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neuralgia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Neuropathy peripheral † 1  2/36 (5.56%)  2/43 (4.65%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nystagmus † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Palatal palsy † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Paraesthesia † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  4/45 (8.89%)  0/3 (0.00%)  9/55 (16.36%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Peripheral motor neuropathy † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Peripheral sensory neuropathy † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Polyneuropathy † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pyramidal tract syndrome † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Sciatica † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Tremor † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
VIth nerve disorder † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Psychiatric disorders                                 
Agitation † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Anxiety † 1  1/36 (2.78%)  3/43 (6.98%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Confusional state † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  2/45 (4.44%)  0/3 (0.00%)  3/55 (5.45%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Depressed mood † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Depression † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  2/13 (15.38%)  1/45 (2.22%)  0/3 (0.00%)  5/55 (9.09%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Emotional disorder † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Insomnia † 1  5/36 (13.89%)  6/43 (13.95%)  0/1 (0.00%)  2/13 (15.38%)  2/45 (4.44%)  1/3 (33.33%)  9/55 (16.36%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Libido decreased † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Mood swings † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Sleep disorder † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Renal and urinary disorders                                 
Acute kidney injury † 1  0/36 (0.00%)  3/43 (6.98%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Chromaturia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haematuria † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  10/55 (18.18%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pollakiuria † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  9/55 (16.36%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Proteinuria † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  3/13 (23.08%)  1/45 (2.22%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Renal failure † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary retention † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Reproductive system and breast disorders                                 
Benign prostatic hyperplasia † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory, thoracic and mediastinal disorders                                 
Cough † 1  4/36 (11.11%)  10/43 (23.26%)  0/1 (0.00%)  3/13 (23.08%)  8/45 (17.78%)  0/3 (0.00%)  30/55 (54.55%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphonia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspnoea † 1  8/36 (22.22%)  7/43 (16.28%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  13/55 (23.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Epistaxis † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  7/55 (12.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Haemoptysis † 1  4/36 (11.11%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hiccups † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  1/3 (33.33%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lung disorder † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nasal congestion † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  20/55 (36.36%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Oropharyngeal pain † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  2/13 (15.38%)  1/45 (2.22%)  0/3 (0.00%)  11/55 (20.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pleural effusion † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonitis † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Productive cough † 1  3/36 (8.33%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  9/55 (16.36%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary embolism † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rhinitis allergic † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rhinorrhoea † 1  2/36 (5.56%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Upper-airway cough syndrome † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  7/55 (12.73%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Wheezing † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin and subcutaneous tissue disorders                                 
Acne † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  2/45 (4.44%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Actinic keratosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  6/55 (10.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Alopecia † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  4/45 (8.89%)  0/3 (0.00%)  2/55 (3.64%)  2/10 (20.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dermatitis acneiform † 1  1/36 (2.78%)  4/43 (9.30%)  0/1 (0.00%)  2/13 (15.38%)  5/45 (11.11%)  0/3 (0.00%)  22/55 (40.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Dry skin † 1  4/36 (11.11%)  4/43 (9.30%)  0/1 (0.00%)  5/13 (38.46%)  2/45 (4.44%)  1/3 (33.33%)  17/55 (30.91%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Eczema † 1  0/36 (0.00%)  5/43 (11.63%)  0/1 (0.00%)  0/13 (0.00%)  2/45 (4.44%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Erythema † 1  1/36 (2.78%)  5/43 (11.63%)  0/1 (0.00%)  3/13 (23.08%)  1/45 (2.22%)  0/3 (0.00%)  5/55 (9.09%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Erythema nodosum † 1  1/36 (2.78%)  2/43 (4.65%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hidradenitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperhidrosis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  8/55 (14.55%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperkeratosis † 1  0/36 (0.00%)  2/43 (4.65%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Ingrowing nail † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Nail discolouration † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Night sweats † 1  3/36 (8.33%)  3/43 (6.98%)  0/1 (0.00%)  3/13 (23.08%)  1/45 (2.22%)  2/3 (66.67%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Palmar-plantar erythrodysaesthesia syndrome † 1  2/36 (5.56%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Papule † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  1/3 (33.33%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Photosensitivity reaction † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  4/55 (7.27%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Piloerection † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Pruritus † 1  4/36 (11.11%)  5/43 (11.63%)  0/1 (0.00%)  6/13 (46.15%)  0/45 (0.00%)  0/3 (0.00%)  10/55 (18.18%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rash † 1  10/36 (27.78%)  12/43 (27.91%)  0/1 (0.00%)  4/13 (30.77%)  12/45 (26.67%)  0/3 (0.00%)  11/55 (20.00%)  3/10 (30.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Rash maculo-papular † 1  3/36 (8.33%)  4/43 (9.30%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  1/3 (33.33%)  19/55 (34.55%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Seborrhoeic dermatitis † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  1/45 (2.22%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin atrophy † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin hyperpigmentation † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  1/3 (33.33%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin lesion † 1  2/36 (5.56%)  2/43 (4.65%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin mass † 1  1/36 (2.78%)  1/43 (2.33%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  2/55 (3.64%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin plaque † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Skin striae † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Xeroderma † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  0/13 (0.00%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Vascular disorders                                 
Flushing † 1  1/36 (2.78%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  1/3 (33.33%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hot flush † 1  0/36 (0.00%)  1/43 (2.33%)  0/1 (0.00%)  0/13 (0.00%)  1/45 (2.22%)  0/3 (0.00%)  3/55 (5.45%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypertension † 1  1/36 (2.78%)  6/43 (13.95%)  0/1 (0.00%)  2/13 (15.38%)  2/45 (4.44%)  1/3 (33.33%)  8/55 (14.55%)  1/10 (10.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Hypotension † 1  5/36 (13.89%)  0/43 (0.00%)  0/1 (0.00%)  2/13 (15.38%)  0/45 (0.00%)  0/3 (0.00%)  8/55 (14.55%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Lymphoedema † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  1/55 (1.82%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
Varicose vein † 1  0/36 (0.00%)  0/43 (0.00%)  0/1 (0.00%)  1/13 (7.69%)  0/45 (0.00%)  0/3 (0.00%)  0/55 (0.00%)  0/10 (0.00%)  /0  /0  /0  /0  /0  /0  /0  /0 
1
Term from vocabulary, MedDRA (24.1)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02034110    
Other Study ID Numbers: 117019
2013-001705-87 ( EudraCT Number )
CDRB436X2201 ( Other Identifier: Novartis )
BRF117019 ( Other Identifier: GlaxoSmithKline )
First Submitted: December 5, 2013
First Posted: January 13, 2014
Results First Submitted: July 4, 2022
Results First Posted: August 21, 2023
Last Update Posted: August 21, 2023