Trial Outcomes & Findings for A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301) (NCT NCT02752074)

NCT ID: NCT02752074

Last Updated: 2025-08-24

Results Overview

Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 706 participants
• Primary outcome timeframe: Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.
• Results posted on: 2025-08-24

Participant Flow

This study was conducted at 135 centers in 23 countries

Participant milestones

Measure	Pembrolizumab + Epacadostat Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Overall Study STARTED	354	352
Overall Study Treated	353	352
Overall Study COMPLETED	198	209
Overall Study NOT COMPLETED	156	143

Reasons for withdrawal

Measure	Pembrolizumab + Epacadostat Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Overall Study Lost to Follow-up	1	4
Overall Study Death	146	129
Overall Study Withdrawal by Subject	9	10

Baseline Characteristics

A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)

Baseline characteristics by cohort

Measure	Pembrolizumab + Epacadostat n=354 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).	Total n=706 Participants Total of all reporting groups
Age, Customized < 65 years	183 Participants n=5 Participants	193 Participants n=7 Participants	376 Participants n=5 Participants
Age, Customized ≥ 65 years	171 Participants n=5 Participants	159 Participants n=7 Participants	330 Participants n=5 Participants
Sex: Female, Male Female	137 Participants n=5 Participants	146 Participants n=7 Participants	283 Participants n=5 Participants
Sex: Female, Male Male	217 Participants n=5 Participants	206 Participants n=7 Participants	423 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=5 Participants	27 Participants n=7 Participants	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	302 Participants n=5 Participants	306 Participants n=7 Participants	608 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants	19 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	40 Participants n=5 Participants	36 Participants n=7 Participants	76 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	311 Participants n=5 Participants	315 Participants n=7 Participants	626 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Fully active	261 Participants n=5 Participants	267 Participants n=7 Participants	528 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Restricted in physically strenuous activity	93 Participants n=5 Participants	85 Participants n=7 Participants	178 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Population: Intent to Treat (ITT) population: consists of all randomized participants.

Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=354 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Progression-free Survival	4.7 months Interval 2.9 to 6.8	4.9 months Interval 2.9 to 6.8

PRIMARY outcome

Timeframe: Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.

Population: Intent to Treat (ITT) population: consists of all randomized participants. OS was analyzed at the time of primary analysis at 6 months. An overall OS was not conducted after the primary analysis since all participants were unblinded, transitioned to monotherapy pembrolizumab and survival follow-up was discontinued.

Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=354 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Overall Survival (OS) Rate at 6 Months	84.1 percent probability Interval 79.8 to 87.5	87.2 percent probability Interval 83.2 to 90.3

SECONDARY outcome

Timeframe: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Population: Intent to Treat (ITT) population: consists of all randomized participants.

Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by independent central review.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=354 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Objective Response Rate (ORR)	121 Participants	111 Participants

SECONDARY outcome

Timeframe: Through up to 90 days after end of treatment, up to 27 months

Population: All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.

Safety and tolerability, as assessed by percentage of participants with adverse events and changes in laboratory parameters.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=353 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events With one or more adverse events	346 Participants	345 Participants
Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events Serious adverse events	99 Participants	100 Participants

SECONDARY outcome

Timeframe: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Population: Intent to Treat (ITT) population: consists of all randomized participants.

Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first. Includes participants with complete response or partial response.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=354 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Duration of Response (DOR)	NA months Interval 0.0 to Median duration not reached due to participants remaining in response at the time of the data cutoff.	NA months Interval 0.0 to Median duration not reached due to participants remaining in response at the time of the data cutoff.

SECONDARY outcome

Timeframe: Through up to 30 days after the end of treatment, up to 25 months

Population: All randomized participants enrolled in the Epacadostat arm currently with melanoma.

Defined as oral dose clearance.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=340 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Apparent Oral Clearance (CL/F) of Epacadostat	59.8 Liter/hour (L/h) Standard Deviation 17.5	—

SECONDARY outcome

Timeframe: Through up to 30 days after the end of treatment, up to 25 months

Population: All randomized participants enrolled in the Epacadostat arm currently with melanoma.

Apparent volume of distribution after administration.

Outcome measures

Measure	Pembrolizumab + Epacadostat n=340 Participants Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Apparent Volume of Distribution (Vd/F) of Epacadostat	139 Liter Standard Deviation 22.5	—

SECONDARY outcome

Timeframe: Through up to 30 days after the end of treatment, up to 25 months

Population: The data was not available nor was the analysis completed for pembrolizumab CL, because participants were unblinded and sample collections and the planned analysis for pembrolizumab CL were discontinued after the interim analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through up to 30 days after the end of treatment, up to 25 months

Population: The data was not available nor was the analysis completed for pembrolizumab V, because participants were unblinded and sample collections and the planned analysis for pembrolizumab V were discontinued after the interim analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through up to 30 days after the end of treatment, up to 25 months

Population: Data was not available nor the analysis completed for the incidence of ADA to pembrolizumab, because all participants were unblinded; sample collections and the planned analysis for ADA were discontinued after the interim analysis.

Evaluate the measurement of anti-drug antibodies (ADA).

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab + Epacadostat

Serious events: 99 serious events

Other events: 327 other events

Deaths: 147 deaths

Pembrolizumab + Placebo

Serious events: 100 serious events

Other events: 325 other events

Deaths: 136 deaths

Serious adverse events

Measure	Pembrolizumab + Epacadostat n=353 participants at risk Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 participants at risk Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Blood and lymphatic system disorders Anaemia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	1.1% 4/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Blood and lymphatic system disorders Neutropenia	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Acute myocardial infarction	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Atrial fibrillation	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Congestive cardiomyopathy	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Extrasystoles	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Myocarditis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Supraventricular tachycardia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Ear and labyrinth disorders Vertigo positional	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Endocrine disorders Adrenal insufficiency	1.1% 4/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Endocrine disorders Hypophysitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.85% 3/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Endocrine disorders Hypothyroidism	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Autoimmune colitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Colitis	1.1% 4/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	1.4% 5/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	2.5% 9/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	1.1% 4/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Gastric haemorrhage	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Gastritis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Intussusception	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Nausea	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Pancreatitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Pancreatitis acute	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Pancreatitis chronic	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	0.85% 3/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Asthenia	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Chest pain	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Death	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Fatigue	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders General physical health deterioration	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Pyrexia	1.1% 4/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.85% 3/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Autoimmune hepatitis	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Bile duct obstruction	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Cholecystitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Hepatic function abnormal	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Hepatitis acute	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Immune system disorders Anaphylactic reaction	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Immune system disorders Cytokine release syndrome	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Immune system disorders Drug hypersensitivity	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Cellulitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Dacryocanaliculitis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Erysipelas	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Infected skin ulcer	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Infection	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Peritonitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Pneumonia	1.4% 5/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Pseudomonas infection	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Respiratory tract infection	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Rhinitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Sepsis	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Septic shock	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Urinary tract infection	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Urosepsis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Viral infection	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Wound infection	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Pubis fracture	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Radiation necrosis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Wound complication	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Alanine aminotransferase increased	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Aspartate aminotransferase increased	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Blood creatinine increased	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Blood potassium increased	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Decreased appetite	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Dehydration	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Hypercalcaemia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Dupuytren's contracture	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pathological fracture	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Scleroderma	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	1.1% 4/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.85% 3/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.85% 3/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour flare	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Chronic inflammatory demyelinating polyradiculoneuropathy	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Dizziness	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Generalised tonic-clonic seizure	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Haemorrhage intracranial	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	1.4% 5/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Hemiplegia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Ischaemic cerebral infarction	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Ischaemic stroke	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Neuralgia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Presyncope	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Syncope	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Tension headache	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Psychiatric disorders Anxiety	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Psychiatric disorders Paranoia	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Acute kidney injury	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.85% 3/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Bladder outlet obstruction	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Hydronephrosis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Nephritis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Nephrolithiasis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Renal failure	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Renal injury	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 5/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.85% 3/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary infarction	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis exfoliative	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Lichen planus	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	0.57% 2/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Skin ulcer	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Deep vein thrombosis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Essential hypertension	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Haematoma	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Hypertension	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Hypotension	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.57% 2/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Lymphoedema	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Eye disorders Retinopathy	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Colitis ischaemic	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Immune-mediated hepatitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Lung infection	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Concussion	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Femur fracture	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Humerus fracture	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the gastrointestinal	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Follicular thyroid cancer	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal adenocarcinoma	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Cerebrovascular accident	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Optic neuritis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Seizure	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Bladder perforation	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Haematuria	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Nephrotic syndrome	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Tubulointerstitial nephritis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Renal and urinary disorders Ureterolithiasis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Emphysema	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Thrombosis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Hepatobiliary disorders Hepatitis	0.28% 1/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.00% 0/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	0.28% 1/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.

Other adverse events

Measure	Pembrolizumab + Epacadostat n=353 participants at risk Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	Pembrolizumab + Placebo n=352 participants at risk Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
Blood and lymphatic system disorders Anaemia	9.9% 35/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	10.2% 36/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Endocrine disorders Hyperthyroidism	6.2% 22/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	7.7% 27/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Endocrine disorders Hypothyroidism	12.5% 44/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.9% 35/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain	10.5% 37/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	10.5% 37/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain upper	6.8% 24/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	4.5% 16/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Constipation	16.4% 58/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	17.6% 62/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	25.5% 90/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	28.4% 100/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Dry mouth	5.4% 19/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	8.5% 30/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Nausea	29.2% 103/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	24.4% 86/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	14.4% 51/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	12.5% 44/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Asthenia	19.3% 68/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	13.1% 46/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Fatigue	28.3% 100/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	26.7% 94/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Oedema peripheral	7.6% 27/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	7.7% 27/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Pyrexia	13.0% 46/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	10.8% 38/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Nasopharyngitis	14.2% 50/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	14.2% 50/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	5.4% 19/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.4% 33/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Urinary tract infection	5.7% 20/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.1% 32/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Alanine aminotransferase increased	11.0% 39/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	7.1% 25/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Amylase increased	7.6% 27/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.7% 34/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Aspartate aminotransferase increased	10.2% 36/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.4% 33/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Lipase increased	10.2% 36/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	11.1% 39/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Investigations Weight decreased	6.2% 22/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	4.8% 17/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Decreased appetite	15.6% 55/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	12.5% 44/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Hyperglycaemia	6.5% 23/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	4.8% 17/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	17.8% 63/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	17.9% 63/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	13.3% 47/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	14.8% 52/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	7.4% 26/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.1% 32/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 32/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	8.0% 28/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Dizziness	9.3% 33/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	9.1% 32/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Headache	18.7% 66/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	21.0% 74/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Psychiatric disorders Anxiety	5.4% 19/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	4.0% 14/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Psychiatric disorders Insomnia	9.9% 35/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	8.8% 31/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	20.7% 73/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	17.9% 63/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 22/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	8.2% 29/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dry skin	6.5% 23/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	6.5% 23/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	23.5% 83/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	28.7% 101/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	21.8% 77/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	23.0% 81/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.9% 21/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	5.1% 18/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Vitiligo	14.4% 51/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	13.6% 48/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Vascular disorders Hypertension	7.6% 27/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	6.0% 21/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
Infections and infestations Influenza	5.4% 19/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	4.8% 17/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.
General disorders Influenza like Illness	4.8% 17/353 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.	6.2% 22/352 • up to 27 months. All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.

Additional Information

Study Director

Incyte Corporation

Phone: 855-463-3463

Email: medinfo@incyte.com

Results disclosure agreements

• Principal investigator is a sponsor employee Clinical Study Agreement.
• Publication restrictions are in place

Restriction type: OTHER