Trial Outcomes & Findings for Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC) (NCT NCT01672853)

NCT ID: NCT01672853

Last Updated: 2019-10-22

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 235 participants
• Primary outcome timeframe: Baseline; Week 96
• Results posted on: 2019-10-22

Participant Flow

Participants were enrolled at study sites in North America and Europe. The first participant was screened on 4 March 2013. The last study visit occurred on 24 August 2016.

298 participants were screened.

Participant milestones

Measure	SIM 75 mg Simtuzumab (SIM) 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo Placebo subcutaneous injections weekly for 96 weeks
Overall Study STARTED	79	77	79
Overall Study COMPLETED	69	60	65
Overall Study NOT COMPLETED	10	17	14

Reasons for withdrawal

Measure	SIM 75 mg Simtuzumab (SIM) 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo Placebo subcutaneous injections weekly for 96 weeks
Overall Study Protocol Specified Criteria for Withdraw	0	4	0
Overall Study Pregnancy	0	1	0
Overall Study Investigator's Discretion	1	0	0
Overall Study Withdrew Consent	5	5	5
Overall Study Adverse Event	4	6	8
Overall Study Lost to Follow-up	0	1	0
Overall Study Randomized but Never Treated	0	0	1

Baseline Characteristics

Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC)

Baseline characteristics by cohort

Measure	SIM 75 mg n=79 Participants SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=77 Participants SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=78 Participants Placebo subcutaneous injections weekly for 96 weeks	Total n=234 Participants Total of all reporting groups
Age, Continuous	45 years STANDARD_DEVIATION 11.3 • n=5 Participants	43 years STANDARD_DEVIATION 10.1 • n=7 Participants	44 years STANDARD_DEVIATION 12.8 • n=5 Participants	44 years STANDARD_DEVIATION 11.5 • n=4 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	25 Participants n=7 Participants	33 Participants n=5 Participants	85 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	52 Participants n=7 Participants	45 Participants n=5 Participants	149 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=5 Participants	73 Participants n=7 Participants	77 Participants n=5 Participants	228 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Black	7 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized White	71 Participants n=5 Participants	68 Participants n=7 Participants	62 Participants n=5 Participants	201 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Canada	16 Participants n=5 Participants	17 Participants n=7 Participants	12 Participants n=5 Participants	45 Participants n=4 Participants
Region of Enrollment Sweden	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment Belgium	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	42 Participants n=5 Participants	35 Participants n=7 Participants	43 Participants n=5 Participants	120 Participants n=4 Participants
Region of Enrollment Denmark	5 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment Italy	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment United Kingdom	5 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants
Region of Enrollment Germany	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment Spain	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment France	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Morphometric Quantitative Collagen (MQC)	5.6 percentage of MQC STANDARD_DEVIATION 5.09 • n=5 Participants	5.6 percentage of MQC STANDARD_DEVIATION 3.36 • n=7 Participants	5.1 percentage of MQC STANDARD_DEVIATION 3.98 • n=5 Participants	5.4 percentage of MQC STANDARD_DEVIATION 4.19 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Full Analysis Set (participants who were randomized into the study and received at least 1 dose of study drug) with available data were analyzed.

Outcome measures

Measure	SIM 75 mg n=61 Participants SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=61 Participants SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=62 Participants Placebo subcutaneous injections weekly for 96 weeks
Change From Baseline in MQC on Liver Biopsy at Week 96	-0.5 percentage of MQC Standard Deviation 5.78	0.5 percentage of MQC Standard Deviation 6.94	0.0 percentage of MQC Standard Deviation 4.76

SECONDARY outcome

Timeframe: First dose date up to Week 96

Population: The Safety Analysis Set included participants who received at least 1 dose of study drug.

Outcome measures

Measure	SIM 75 mg n=79 Participants SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=77 Participants SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=78 Participants Placebo subcutaneous injections weekly for 96 weeks
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	5.1 percentage of participants	7.8 percentage of participants	10.3 percentage of participants

SECONDARY outcome

Timeframe: First dose date up to Week 96

Population: Participants in the Safety Analysis Set were analyzed.

The average SIM exposure was summarized.

Outcome measures

Measure	SIM 75 mg n=79 Participants SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=77 Participants SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=78 Participants Placebo subcutaneous injections weekly for 96 weeks
Study Drug Exposure	92.0 weeks Standard Deviation 15.33	83.8 weeks Standard Deviation 26.12	87.4 weeks Standard Deviation 22.35

SECONDARY outcome

Timeframe: First dose date up to Week 96 plus 30 days

Population: Participants in the Safety Analysis Set with at least one post-baseline measurement were analyzed.

A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening)].

Outcome measures

Measure	SIM 75 mg n=79 Participants SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=77 Participants SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=78 Participants Placebo subcutaneous injections weekly for 96 weeks
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality Grade 1	11.4 percentage of participants	16.9 percentage of participants	17.9 percentage of participants
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality Grade 2	26.6 percentage of participants	20.8 percentage of participants	25.6 percentage of participants
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality Grade 3	48.1 percentage of participants	46.8 percentage of participants	48.7 percentage of participants
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality Grade 4	11.4 percentage of participants	13.0 percentage of participants	7.7 percentage of participants

Adverse Events

SIM 75 mg

Serious events: 16 serious events

Other events: 71 other events

Deaths: 0 deaths

SIM 125 mg

Serious events: 23 serious events

Other events: 72 other events

Deaths: 0 deaths

Placebo

Serious events: 21 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Measure	SIM 75 mg n=79 participants at risk SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=77 participants at risk SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=78 participants at risk Placebo subcutaneous injections weekly for 96 weeks
Blood and lymphatic system disorders Leukocytosis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Cardiac disorders Ventricular tachycardia	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Diverticular perforation	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Haematemesis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Haematochezia	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Melaena	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophageal varices haemorrhage	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Systemic inflammatory response syndrome	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Bile duct stenosis	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Bile duct stone	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Cholangitis	7.6% 6/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Cholangitis acute	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Cholelithiasis	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Gallbladder perforation	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Jaundice cholestatic	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Cholangitis infective	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Gastrointestinal infection	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Infected skin ulcer	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Pelvic abscess	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Peritonitis	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Sepsis	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Septic shock	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Streptococcal bacteraemia	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Intestinal anastomosis complication	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Post procedural complication	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Postoperative fever	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Procedural complication	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Stoma obstruction	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Investigations Liver function test increased	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign biliary neoplasm	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenoma	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Psychiatric disorders Depression	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Psychiatric disorders Post-traumatic stress disorder	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Renal and urinary disorders Calculus urinary	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Renal and urinary disorders Renal colic	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Drug eruption	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Vascular disorders Thrombophlebitis	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.

Other adverse events

Measure	SIM 75 mg n=79 participants at risk SIM 75 mg subcutaneous injections weekly for 96 weeks	SIM 125 mg n=77 participants at risk SIM 125 mg subcutaneous injections weekly for 96 weeks	Placebo n=78 participants at risk Placebo subcutaneous injections weekly for 96 weeks
Blood and lymphatic system disorders Anaemia	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.2% 4/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	7.7% 6/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	16.5% 13/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	23.4% 18/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	21.8% 17/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	22.8% 18/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	18.2% 14/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	23.1% 18/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis ulcerative	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.4% 5/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	8.9% 7/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.0% 7/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	24.1% 19/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	19.5% 15/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	19.2% 15/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	11.5% 9/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.4% 5/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	20.3% 16/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	22.1% 17/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	21.8% 17/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Varices oesophageal	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	11.4% 9/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.0% 7/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Asthenia	1.3% 1/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.2% 4/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Fatigue	24.1% 19/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	27.3% 21/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	20.5% 16/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Influenza like illness	3.8% 3/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.2% 4/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Injection site erythema	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Injection site pain	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	7.8% 6/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.4% 5/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
General disorders Pyrexia	13.9% 11/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	13.0% 10/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	16.7% 13/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Cholangitis	7.6% 6/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	7.8% 6/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Hepatobiliary disorders Jaundice	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.2% 4/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Bronchitis	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.0% 7/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis viral	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Influenza	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.0% 7/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Lower respiratory tract infection	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	24.1% 19/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	22.1% 17/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	17.9% 14/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Sinusitis	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	14.3% 11/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.4% 5/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	13.9% 11/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	11.7% 9/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	12.8% 10/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	7.6% 6/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.2% 4/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	0.00% 0/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Procedural pain	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.1% 7/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.0% 7/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.4% 5/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	15.6% 12/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	12.8% 10/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	10.1% 8/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	10.4% 8/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	11.5% 9/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	8.9% 7/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.1% 4/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.1% 7/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	8.9% 7/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Nervous system disorders Dizziness	7.6% 6/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Nervous system disorders Headache	22.8% 18/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	15.6% 12/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	21.8% 17/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	2.5% 2/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	6.5% 5/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	17.7% 14/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.1% 7/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	9.0% 7/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.3% 5/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.9% 3/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	3.8% 3/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.2% 4/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	1.3% 1/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	26.6% 21/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	28.6% 22/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	39.7% 31/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	12.7% 10/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	3.8% 3/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.
Vascular disorders Hypertension	3.8% 3/79 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	2.6% 2/77 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.	5.1% 4/78 • First dose date up to Week 96 plus 30 days The Safety Analysis Set included participants who received at least one dose of study drug.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: GileadClinicalTrials@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
• Publication restrictions are in place

Restriction type: OTHER