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Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01866319
Recruitment Status : Completed
First Posted : May 31, 2013
Results First Posted : January 14, 2016
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Biological: Pembrolizumab
Biological: Ipilimumab
Enrollment 834
Recruitment Details Participants with advanced melanoma were recruited to receive ipilimumab once every 3 weeks (Q3W), or a primary course of pembrolizumab administered every 2 weeks (Q2W) or every 3 weeks (Q3W).
Pre-assignment Details 834 participants were randomized 1:1:1 to receive ipilimumab Q3W, pembrolizumab Q2W, or pembrolizumab Q3W. For participants receiving pembrolizumab, all safety and efficacy results data reported are for the primary pembrolizumab course received.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months). Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months. Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Period Title: Overall Study
Started 278 279 277
Treated 256 278 277
Completed 71 101 97
Not Completed 207 178 180
Reason Not Completed
Adverse Event             12             5             9
Clinical progression             3             2             2
Death             153             154             147
Lost to Follow-up             6             3             8
Physician Decision             1             0             1
Protocol Violation             0             0             1
Withdrawal by Subject             32             14             12
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W Total
Hide Arm/Group Description Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months). Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months. Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months. Total of all reporting groups
Overall Number of Baseline Participants 278 279 277 834
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants. Participants were included in the group to which they were randomized for Baseline Characteristics.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 278 participants 279 participants 277 participants 834 participants
59.9  (14.2) 59.9  (14.6) 61.2  (13.6) 60.3  (14.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 278 participants 279 participants 277 participants 834 participants
Female
116
  41.7%
118
  42.3%
103
  37.2%
337
  40.4%
Male
162
  58.3%
161
  57.7%
174
  62.8%
497
  59.6%
1.Primary Outcome
Title Progression-free Survival (PFS) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Radiology Plus Oncology Review (IRO)
Hide Description PFS was defined as the time from randomization to the first documented disease progression, based on blinded Independent Radiology plus Oncology review (IRO) using RECIST 1.1, or death due to any cause, whichever occurred first. Disease progression was defined as a 20% or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of new lesions. The primary analysis of PFS was performed at the time of the first protocol pre-specified statistical analysis, with data cut-off of 03-Sep-2014.
Time Frame Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population, comprising all participants as randomized to a study arm.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description:
Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).
Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.
Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Overall Number of Participants Analyzed 278 279 277
Median (95% Confidence Interval)
Unit of Measure: Months
2.8
(2.8 to 2.9)
5.5
(3.4 to 6.9)
4.1
(2.9 to 6.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q2W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), programmed cell death ligand 1 (PD-L1) status (positive vs. negative) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.46 to 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q3W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), programmed cell death ligand 1 (PD-L1) status (positive vs. negative) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.47 to 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab Q2W, Pembrolizumab Q3W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), programmed cell death ligand 1 (PD-L1) status (positive vs. negative) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75869
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.77 to 1.21
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Overall Survival (OS) at 12 Months
Hide Description OS was defined as the time from randomization to death due to any cause. The percentage of participants with OS (OS rate) at 12 months was reported for each arm. The reported percentage was estimated using a product-limit (Kaplan-Meier) method for censored data; data were censored at the date of cut-off. The primary analysis of OS was performed at the time of the second protocol pre-specified statistical analysis, with data cut-off of 03-Mar-2015.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population, comprising all participants as randomized to a study arm.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description:
Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).
Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.
Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Overall Number of Participants Analyzed 278 279 277
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
58.2
(51.8 to 64.0)
74.1
(68.5 to 78.9)
68.4
(62.5 to 73.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q2W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00052
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.47 to 0.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q3W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00358
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.52 to 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab Q2W, Pembrolizumab Q3W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51319
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval 95%
0.67 to 1.22
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by IRO
Hide Description ORR was defined as the percentage of the participants with a best tumor response of complete response (CR: disappearance of all target lesions with any pathological lymph nodes having a reduction in short axis to <10 mm) or partial response (PR: ≥30% decrease in the sum of diameters of target lesions), based on IRO using RECIST 1.1. The primary analysis of ORR was performed at the time of the first protocol pre-specified statistical analysis, with data cut-off of 03-Sep-2014.
Time Frame Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population, comprising all participants as randomized to a study arm.
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description:
Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).
Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.
Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Overall Number of Participants Analyzed 278 279 277
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
11.9
(8.3 to 16.3)
33.7
(28.2 to 39.6)
32.9
(27.4 to 38.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q2W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00013
Comments [Not Specified]
Method Miettinen & Nurmimen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value 16.1
Confidence Interval (2-Sided) 95%
7.8 to 24.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ipilimumab, Pembrolizumab Q3W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00002
Comments [Not Specified]
Method Miettinen & Nurmimen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value 17.2
Confidence Interval (2-Sided) 95%
9.5 to 25.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pembrolizumab Q2W, Pembrolizumab Q3W
Comments Statistical testing was stratified by line of therapy (1st vs. 2nd), PD-L1) status (positive vs. negative) and ECOG performance status (0 vs. 1)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82636
Comments [Not Specified]
Method Miettinen & Nurmimen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value -1.1
Confidence Interval 95%
-10.6 to 8.6
Estimation Comments [Not Specified]
Time Frame Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019)
Adverse Event Reporting Description

All-Cause Mortality table includes all randomized participants.

Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

 
Arm/Group Title Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Hide Arm/Group Description Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months). Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months. Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
All-Cause Mortality
Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   173/278 (62.23%)      166/279 (59.50%)      162/277 (58.48%)    
Hide Serious Adverse Events
Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   77/256 (30.08%)      89/278 (32.01%)      90/277 (32.49%)    
Blood and lymphatic system disorders       
Anaemia  1  0/256 (0.00%)  0 2/278 (0.72%)  2 2/277 (0.72%)  2
Anaemia aggravated  1  0/256 (0.00%)  0 0/278 (0.00%)  0 3/277 (1.08%)  3
Lymph nodes enlarged  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Thrombocytopenia  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  2
Cardiac disorders       
Acute coronary syndrome  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Angina unstable  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Atrial fibrillation  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Atrial flutter  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cardiac failure congestive  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Congestive cardiac failure aggravated  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  2
Decompensation cardiac  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  2
Heart attack  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Paroxysmal atrial fibrillation  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pericardial effusion  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Congenital, familial and genetic disorders       
Pyloric stenosis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Ear and labyrinth disorders       
Hearing impaired  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Endocrine disorders       
Adrenal insufficiency  1  1/256 (0.39%)  1 2/278 (0.72%)  2 0/277 (0.00%)  0
Adrenomegaly  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypophysitis  1  2/256 (0.78%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Hypopituitarism  1  1/256 (0.39%)  1 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypothyroidism  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Panhypopituitarism  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Eye disorders       
Diplopia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Neovascular glaucoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Papilloedema  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Gastrointestinal disorders       
Abdominal distension  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Abdominal pain  1  2/256 (0.78%)  2 1/278 (0.36%)  1 2/277 (0.72%)  2
Abdominal pain lower  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Anal fistula  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Autoimmune colitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Autoimmune pancreatitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Blood in stool  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Colitis  1  16/256 (6.25%)  18 6/278 (2.16%)  6 6/277 (2.17%)  6
Constipation  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Diarrhoea  1  9/256 (3.52%)  9 7/278 (2.52%)  7 3/277 (1.08%)  3
Enteritis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Enterocolitis  1  2/256 (0.78%)  2 0/278 (0.00%)  0 0/277 (0.00%)  0
Gastritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  2
Gastrooesophagitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Haemorrhage of digestive tract  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Ileus  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Intestinal obstruction  1  0/256 (0.00%)  0 2/278 (0.72%)  3 0/277 (0.00%)  0
Intestinal stenosis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Intussusception  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Lower gastrointestinal bleeding  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Mouth necrosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Nausea  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pancreatitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pancreatitis acute  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pancreatitis aggravated  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Partial small intestinal obstruction  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Reflux oesophagitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Sigmoiditis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Small intestinal obstruction  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Vomiting  1  2/256 (0.78%)  2 0/278 (0.00%)  0 0/277 (0.00%)  0
General disorders       
Anasarca  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Asthenia  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Cardiac death  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Face oedema  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Fatigue aggravated  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Fever  1  4/256 (1.56%)  4 1/278 (0.36%)  1 0/277 (0.00%)  0
General body pain  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
General physical health deterioration  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Malaise  1  0/256 (0.00%)  0 2/278 (0.72%)  2 1/277 (0.36%)  1
Reduced general condition  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Unknown cause of death  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hepatobiliary disorders       
Autoimmune hepatitis  1  2/256 (0.78%)  2 4/278 (1.44%)  4 1/277 (0.36%)  1
Bile duct obstruction  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Biliary colic  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Biliary dilatation  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Cholangitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cholecystitis  1  0/256 (0.00%)  0 2/278 (0.72%)  2 0/277 (0.00%)  0
Cytolytic hepatitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Drug-induced hepatitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  2
Hepatic cytolysis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Hepatitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Hepatitis toxic  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Obstructive jaundice  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Immune system disorders       
Anaphylactoid reaction  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Drug hypersensitivity  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypersensitivity reaction  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Infections and infestations       
Bladder infection  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Bronchial infection  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Cellulitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  2
Cellulitis aggravated  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cellulitis of oral soft tissues  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Cellulitis of upper arm  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Central line infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Clostridium difficile colitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Colonic abscess  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Cytomegalovirus infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Encephalitis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Erysipelas  1  1/256 (0.39%)  1 1/278 (0.36%)  1 1/277 (0.36%)  1
Escherichia bacteraemia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Gastroenteritis  1  0/256 (0.00%)  0 2/278 (0.72%)  2 0/277 (0.00%)  0
Infection  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Klebsiella sepsis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Lung infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 2/277 (0.72%)  2
Meningoencephalitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Myelitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pneumonia  1  1/256 (0.39%)  1 2/278 (0.72%)  2 1/277 (0.36%)  1
Pneumonia viral  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pseudomembranous colitis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pyelonephritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Respiratory tract infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Sepsis  1  2/256 (0.78%)  2 2/278 (0.72%)  2 2/277 (0.72%)  2
Septic shock  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Septicaemia gram-negative NOS  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Sinusitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Soft tissue infection  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Urinary tract infection  1  1/256 (0.39%)  1 1/278 (0.36%)  1 1/277 (0.36%)  1
Injury, poisoning and procedural complications       
Facial bones fracture  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Radiation necrosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Rib fracture  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Shoulder injury  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Wound breakdown  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  2/256 (0.78%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Aspartate aminotransferase increased  1  1/256 (0.39%)  1 1/278 (0.36%)  1 2/277 (0.72%)  2
Bilirubin total increased  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Intraocular pressure decreased  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Liver function test abnormal  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Diabetic ketoacidosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Failure to thrive  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Gout  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypercalcaemia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Hypoalbuminaemia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypokalaemia  1  0/256 (0.00%)  0 2/278 (0.72%)  2 1/277 (0.36%)  1
Hyponatraemia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 2/277 (0.72%)  2
Hyponatremia aggravated  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Metabolic disorder  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Type 1 diabetes mellitus  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Musculoskeletal and connective tissue disorders       
Back pain aggravated  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Hips osteoarthritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Low back pain  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Myalgia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pain in heel  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Pain in leg  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Pathologic fracture of femur  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pathologic fracture of humerus  1  0/256 (0.00%)  0 2/278 (0.72%)  2 0/277 (0.00%)  0
Pathological fracture  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Prolapsed lumbar disc  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Psoriatic arthritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Seronegative arthritis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Unilateral leg pain  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-cell chronic lymphocytic leukaemia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Basal cell carcinoma  1  0/256 (0.00%)  0 5/278 (1.80%)  7 2/277 (0.72%)  2
Basal squamous cell carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Desmoplastic melanoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Epidermoid carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Huerthle cell carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Intra-epidermal carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Intracranial tumour bleeding  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Intracranial tumour haemorrhage  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Lung neoplasm malignant  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Lymphangiosis carcinomatosa  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Melanoma  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Metastases to brain  1  2/256 (0.78%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Metastatic malignant melanoma  1  0/256 (0.00%)  0 2/278 (0.72%)  2 0/277 (0.00%)  0
Neoplasm malignant  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Papillary thyroid cancer  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Papilloma  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Prostate cancer  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Renal cell carcinoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Signet-ring cell adenocarcinoma gastric  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Squamous cell carcinoma  1  1/256 (0.39%)  1 2/278 (0.72%)  2 1/277 (0.36%)  1
Squamous cell carcinoma of skin  1  1/256 (0.39%)  1 1/278 (0.36%)  1 1/277 (0.36%)  1
Superficial basal cell carcinoma  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Thyroid papillary carcinoma  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Tumour bleeding  1  3/256 (1.17%)  3 0/278 (0.00%)  0 0/277 (0.00%)  0
Tumour pain  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Nervous system disorders       
Bell's palsy  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Brain oedema  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Carotid artery stenosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Cerebral ischaemia  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Cerebral oedema  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Cerebrovascular accident  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Convulsions aggravated  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Dizziness  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Encephalopathy  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Epilepsy  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Guillain-Barre syndrome  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Haemorrhage brain  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Haemorrhage intracranial  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Haemorrhagic stroke  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Horner's syndrome  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Hydrocephalus  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Paraneoplastic limbic encephalitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Partial seizures  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Sciatica  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Seizure  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Spinal cord compression  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Syncope  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Transient ischaemic attack  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Vasogenic cerebral oedema  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Psychiatric disorders       
Acute delirium  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Completed suicide  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Confusion  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Depression aggravated  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Dysphoria  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Mental status changes  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Acute renal insufficiency  1  0/256 (0.00%)  0 2/278 (0.72%)  2 1/277 (0.36%)  2
Autoimmune nephritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Hydronephrosis  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Nephritis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Nephritis interstitial  1  1/256 (0.39%)  1 0/278 (0.00%)  0 2/277 (0.72%)  2
Renal disorder  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Renal failure  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Renal insufficiency  1  1/256 (0.39%)  1 0/278 (0.00%)  0 1/277 (0.36%)  1
Tubulointerstitial nephritis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Urinary retention  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Reproductive system and breast disorders       
Prostatitis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchospasm  1  0/256 (0.00%)  0 1/278 (0.36%)  2 0/277 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Chronic obstructive pulmonary disease exacerbation  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  2
Cough  1  0/256 (0.00%)  0 1/278 (0.36%)  1 1/277 (0.36%)  1
Dyspnoea  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Dyspnoea exacerbated  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Haemoptysis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 2/277 (0.72%)  2
Hypoxia  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Pleural effusion  1  1/256 (0.39%)  2 1/278 (0.36%)  1 1/277 (0.36%)  1
Pneumonitis  1  1/256 (0.39%)  1 1/278 (0.36%)  1 4/277 (1.44%)  4
Pneumothorax  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Pulmonary embolism  1  0/256 (0.00%)  0 1/278 (0.36%)  1 4/277 (1.44%)  4
Pulmonary thrombosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Skin and subcutaneous tissue disorders       
Bullous lichen planus  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Bullous pemphigoid  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Drug rash  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Rash  1  1/256 (0.39%)  1 0/278 (0.00%)  0 2/277 (0.72%)  2
Vascular disorders       
Aortic stenosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Arterial stenosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Arterial thrombosis  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Deep vein thrombosis  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Haematoma  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Hypotension  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Lymphoedema  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Orthostatic hypotension  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Peripheral vascular disorder  1  0/256 (0.00%)  0 0/278 (0.00%)  0 1/277 (0.36%)  1
Poor venous access  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Superior vena cava occlusion  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
Thrombosis leg  1  1/256 (0.39%)  1 0/278 (0.00%)  0 0/277 (0.00%)  0
Vein disorder  1  0/256 (0.00%)  0 1/278 (0.36%)  1 0/277 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab Pembrolizumab Q2W Pembrolizumab Q3W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   220/256 (85.94%)      257/278 (92.45%)      247/277 (89.17%)    
Blood and lymphatic system disorders       
Anaemia  1  12/256 (4.69%)  14 34/278 (12.23%)  44 23/277 (8.30%)  28
Endocrine disorders       
Hyperthyroidism  1  6/256 (2.34%)  6 17/278 (6.12%)  19 12/277 (4.33%)  12
Hypothyroidism  1  5/256 (1.95%)  5 29/278 (10.43%)  31 25/277 (9.03%)  26
Gastrointestinal disorders       
Abdominal pain  1  16/256 (6.25%)  19 29/278 (10.43%)  37 18/277 (6.50%)  19
Constipation  1  29/256 (11.33%)  32 53/278 (19.06%)  78 39/277 (14.08%)  47
Diarrhoea  1  69/256 (26.95%)  91 82/278 (29.50%)  162 76/277 (27.44%)  116
Dry mouth  1  1/256 (0.39%)  1 26/278 (9.35%)  27 20/277 (7.22%)  21
Nausea  1  55/256 (21.48%)  66 73/278 (26.26%)  90 70/277 (25.27%)  88
Vomiting  1  31/256 (12.11%)  35 45/278 (16.19%)  66 27/277 (9.75%)  32
General disorders       
Asthenia  1  26/256 (10.16%)  29 45/278 (16.19%)  92 41/277 (14.80%)  56
Fatigue  1  73/256 (28.52%)  78 90/278 (32.37%)  125 85/277 (30.69%)  116
Fever  1  20/256 (7.81%)  22 29/278 (10.43%)  40 21/277 (7.58%)  35
Flu-like symptoms  1  8/256 (3.13%)  9 21/278 (7.55%)  23 14/277 (5.05%)  27
Infections and infestations       
Common cold syndrome  1  9/256 (3.52%)  9 21/278 (7.55%)  32 15/277 (5.42%)  18
Upper respiratory tract infection  1  11/256 (4.30%)  11 31/278 (11.15%)  43 21/277 (7.58%)  25
Urinary tract infection  1  10/256 (3.91%)  11 22/278 (7.91%)  33 14/277 (5.05%)  19
Investigations       
Alanine aminotransferase increased  1  12/256 (4.69%)  13 21/278 (7.55%)  32 16/277 (5.78%)  19
Aspartate aminotransferase increased  1  12/256 (4.69%)  13 22/278 (7.91%)  35 12/277 (4.33%)  17
Lactate dehydrogenase increased  1  6/256 (2.34%)  6 14/278 (5.04%)  25 6/277 (2.17%)  11
Weight decreased  1  13/256 (5.08%)  13 20/278 (7.19%)  21 26/277 (9.39%)  28
Metabolism and nutrition disorders       
Anorexia  1  24/256 (9.38%)  27 31/278 (11.15%)  39 35/277 (12.64%)  36
Hypokalaemia  1  5/256 (1.95%)  7 16/278 (5.76%)  34 13/277 (4.69%)  14
Musculoskeletal and connective tissue disorders       
Arthralgia  1  18/256 (7.03%)  18 41/278 (14.75%)  63 39/277 (14.08%)  42
Back pain  1  8/256 (3.13%)  8 29/278 (10.43%)  32 11/277 (3.97%)  12
Knee pain  1  6/256 (2.34%)  6 15/278 (5.40%)  21 8/277 (2.89%)  8
Low back pain  1  5/256 (1.95%)  5 17/278 (6.12%)  19 12/277 (4.33%)  14
Myalgia  1  8/256 (3.13%)  8 32/278 (11.51%)  38 15/277 (5.42%)  18
Shoulder pain  1  8/256 (3.13%)  9 21/278 (7.55%)  26 12/277 (4.33%)  12
Nervous system disorders       
Dizziness  1  9/256 (3.52%)  9 27/278 (9.71%)  34 22/277 (7.94%)  26
Headache  1  27/256 (10.55%)  29 45/278 (16.19%)  72 33/277 (11.91%)  58
Psychiatric disorders       
Anxiety  1  4/256 (1.56%)  4 14/278 (5.04%)  14 10/277 (3.61%)  10
Insomnia  1  14/256 (5.47%)  14 28/278 (10.07%)  33 20/277 (7.22%)  20
Respiratory, thoracic and mediastinal disorders       
Cough  1  16/256 (6.25%)  17 58/278 (20.86%)  75 43/277 (15.52%)  48
Dry cough  1  2/256 (0.78%)  2 9/278 (3.24%)  10 15/277 (5.42%)  16
Dyspnoea  1  15/256 (5.86%)  16 30/278 (10.79%)  32 27/277 (9.75%)  27
Sore throat  1  4/256 (1.56%)  5 16/278 (5.76%)  16 5/277 (1.81%)  5
Skin and subcutaneous tissue disorders       
Dry skin  1  6/256 (2.34%)  6 19/278 (6.83%)  20 17/277 (6.14%)  17
Pruritus  1  65/256 (25.39%)  76 68/278 (24.46%)  99 59/277 (21.30%)  83
Rash  1  28/256 (10.94%)  29 37/278 (13.31%)  55 36/277 (13.00%)  51
Rash maculo-papular  1  8/256 (3.13%)  8 17/278 (6.12%)  23 10/277 (3.61%)  15
Vitiligo  1  4/256 (1.56%)  4 34/278 (12.23%)  36 42/277 (15.16%)  45
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
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 Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01866319    
Other Study ID Numbers: 3475-006
2012-004907-10 ( EudraCT Number )
MK-3475-006 ( Other Identifier: Merck Protocol Number )
First Submitted: May 28, 2013
First Posted: May 31, 2013
Results First Submitted: December 9, 2015
Results First Posted: January 14, 2016
Last Update Posted: June 2, 2020