Trial Outcomes & Findings for Simtuzumab (SIM, GS-6624) in the Treatment of Cirrhosis Due to NASH (NCT NCT01672879)

NCT ID: NCT01672879

Last Updated: 2019-03-27

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 259 participants
• Primary outcome timeframe: Baseline to Week 96
• Results posted on: 2019-03-27

Participant Flow

Participants were enrolled at study sites in Europe and North America. The first participant was screened on 29 October 2012. The last study visit occurred on 03 January 2017.

453 participants were screened.

Participant milestones

Measure	SIM 200 mg Blinded Phase: Participants received simtuzumab (SIM) 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	SIM 700 mg Blinded Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	Placebo Blinded Phase: Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Blinded Phase (Up to 240 Weeks) STARTED	87	86	86
Blinded Phase (Up to 240 Weeks) COMPLETED	0	0	0
Blinded Phase (Up to 240 Weeks) NOT COMPLETED	87	86	86
Open-Label Phase (Up to 240 Weeks) STARTED	15	17	8
Open-Label Phase (Up to 240 Weeks) COMPLETED	0	0	0
Open-Label Phase (Up to 240 Weeks) NOT COMPLETED	15	17	8

Reasons for withdrawal

Measure	SIM 200 mg Blinded Phase: Participants received simtuzumab (SIM) 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	SIM 700 mg Blinded Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	Placebo Blinded Phase: Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Blinded Phase (Up to 240 Weeks) Study Terminated by Sponsor	43	55	61
Blinded Phase (Up to 240 Weeks) Withdrew Consent	14	7	6
Blinded Phase (Up to 240 Weeks) Adverse Event	5	2	7
Blinded Phase (Up to 240 Weeks) Lost to Follow-up	4	3	1
Blinded Phase (Up to 240 Weeks) Investigator's Discretion	5	0	2
Blinded Phase (Up to 240 Weeks) Death	0	2	0
Blinded Phase (Up to 240 Weeks) Missing	1	0	0
Blinded Phase (Up to 240 Weeks) Randomized but Never Treated	0	0	1
Blinded Phase (Up to 240 Weeks) Met Protocol-Specified Reason(s)	15	17	8
Open-Label Phase (Up to 240 Weeks) Study Terminated by Sponsor	8	16	6
Open-Label Phase (Up to 240 Weeks) Adverse Event	5	1	1
Open-Label Phase (Up to 240 Weeks) Investigator's Discretion	1	0	1
Open-Label Phase (Up to 240 Weeks) Progressive Disease	1	0	0

Baseline Characteristics

Full Analysis Set included all enrolled participants who were randomized and received at least 1 dose of study drug. Only participants with available baseline data were analyzed.

Baseline characteristics by cohort

Measure	SIM 200 mg n=87 Participants Blinded Phase: Participants received SIM 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	SIM 700 mg n=86 Participants Blinded Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	Placebo n=85 Participants Blinded Phase: Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	Total n=258 Participants Total of all reporting groups
Age, Continuous	56 years STANDARD_DEVIATION 7.2 • n=87 Participants	55 years STANDARD_DEVIATION 7.3 • n=86 Participants	56 years STANDARD_DEVIATION 7.8 • n=85 Participants	55 years STANDARD_DEVIATION 7.4 • n=258 Participants
Sex: Female, Male Female	53 Participants n=87 Participants	54 Participants n=86 Participants	56 Participants n=85 Participants	163 Participants n=258 Participants
Sex: Female, Male Male	34 Participants n=87 Participants	32 Participants n=86 Participants	29 Participants n=85 Participants	95 Participants n=258 Participants
Race/Ethnicity, Customized Race · Asian	3 Participants n=87 Participants	1 Participants n=86 Participants	0 Participants n=85 Participants	4 Participants n=258 Participants
Race/Ethnicity, Customized Race · Black	2 Participants n=87 Participants	3 Participants n=86 Participants	1 Participants n=85 Participants	6 Participants n=258 Participants
Race/Ethnicity, Customized Race · White	80 Participants n=87 Participants	75 Participants n=86 Participants	83 Participants n=85 Participants	238 Participants n=258 Participants
Race/Ethnicity, Customized Race · Other	2 Participants n=87 Participants	7 Participants n=86 Participants	1 Participants n=85 Participants	10 Participants n=258 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	12 Participants n=87 Participants	17 Participants n=86 Participants	10 Participants n=85 Participants	39 Participants n=258 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	75 Participants n=87 Participants	69 Participants n=86 Participants	75 Participants n=85 Participants	219 Participants n=258 Participants
Region of Enrollment United States	67 Participants n=87 Participants	68 Participants n=86 Participants	76 Participants n=85 Participants	211 Participants n=258 Participants
Region of Enrollment France	6 Participants n=87 Participants	4 Participants n=86 Participants	3 Participants n=85 Participants	13 Participants n=258 Participants
Region of Enrollment Canada	5 Participants n=87 Participants	1 Participants n=86 Participants	2 Participants n=85 Participants	8 Participants n=258 Participants
Region of Enrollment Germany	1 Participants n=87 Participants	4 Participants n=86 Participants	3 Participants n=85 Participants	8 Participants n=258 Participants
Region of Enrollment Spain	3 Participants n=87 Participants	5 Participants n=86 Participants	0 Participants n=85 Participants	8 Participants n=258 Participants
Region of Enrollment United Kingdom	3 Participants n=87 Participants	3 Participants n=86 Participants	1 Participants n=85 Participants	7 Participants n=258 Participants
Region of Enrollment Italy	2 Participants n=87 Participants	1 Participants n=86 Participants	0 Participants n=85 Participants	3 Participants n=258 Participants
Hepatic Venous Pressure Gradient (HVPG)	12.9 mmHg STANDARD_DEVIATION 5.10 • n=87 Participants • Full Analysis Set included all enrolled participants who were randomized and received at least 1 dose of study drug. Only participants with available baseline data were analyzed.	12.8 mmHg STANDARD_DEVIATION 5.37 • n=85 Participants • Full Analysis Set included all enrolled participants who were randomized and received at least 1 dose of study drug. Only participants with available baseline data were analyzed.	13.0 mmHg STANDARD_DEVIATION 5.25 • n=84 Participants • Full Analysis Set included all enrolled participants who were randomized and received at least 1 dose of study drug. Only participants with available baseline data were analyzed.	12.9 mmHg STANDARD_DEVIATION 5.22 • n=256 Participants • Full Analysis Set included all enrolled participants who were randomized and received at least 1 dose of study drug. Only participants with available baseline data were analyzed.

PRIMARY outcome

Timeframe: Baseline to Week 96

Population: Participants in the Full Analysis Set with available data were analyzed.

Outcome measures

Measure	SIM 200 mg n=63 Participants Blinded Phase: Participants received SIM 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	SIM 700 mg n=66 Participants Blinded Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	Placebo n=68 Participants Blinded Phase: Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG)	-0.1 mmHg Standard Deviation 3.76	0.0 mmHg Standard Deviation 4.23	-0.1 mmHg Standard Deviation 4.01

PRIMARY outcome

Timeframe: Baseline up to the time of clinical event or last dose date (maximum: 240 weeks in Blinded Phase); which ever occurred first

Population: Participants in the Full Analysis Set were analyzed.

Event free survival (EFS) was the primary clinical efficacy endpoint and was assessed by time to first liver-related event or death, whichever occurs first. Liver-related events included any of the following:

• Liver transplantation
• Qualification for liver transplantation
• Model for End-Stage Liver Disease (MELD) ≥ 15
• Events indicative of hepatic decompensation
• Esophageal variceal bleeding
• Ascites
• Hepatic Encephalopathy
• ≥ 2 point increase in Child Pugh-Turcotte (CPT) score
• Newly diagnosed varices in a subject without prior varices

Outcome measures

Measure	SIM 200 mg n=87 Participants Blinded Phase: Participants received SIM 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	SIM 700 mg n=86 Participants Blinded Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.	Placebo n=85 Participants Blinded Phase: Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks. Open-Label Phase: Open-Label Phase: Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to an additional 240 weeks.
Event-Free Survival (EFS) Using Kaplan-Meier	NA months Data was not estimable as more than 50% of participants were censored.	NA months Data was not estimable as more than 50% of participants were censored.	NA months Data was not estimable as more than 50% of participants were censored.

Adverse Events

Blinded Phase: SIM 200 mg

Serious events: 37 serious events

Other events: 85 other events

Deaths: 0 deaths

Blinded Phase: SIM 700 mg

Serious events: 36 serious events

Other events: 81 other events

Deaths: 0 deaths

Blinded Phase: Placebo

Serious events: 25 serious events

Other events: 83 other events

Deaths: 0 deaths

Open-Label Phase: SIM 700 mg

Serious events: 17 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Blinded Phase: SIM 200 mg n=87 participants at risk Adverse events recorded in this group occurred during the Blinded Phase. Participants received SIM 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks.	Blinded Phase: SIM 700 mg n=86 participants at risk Adverse events recorded in this group occurred during the Blinded Phase. Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks.	Blinded Phase: Placebo n=85 participants at risk Adverse events recorded in this group occurred during the Blinded Phase. Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks.	Open-Label Phase: SIM 700 mg n=40 participants at risk All participants who completed the randomized phase through the Week 240 visit, or who had an adjudicated clinical event prior to completing the randomized phase, were offered the opportunity to receive open-label SIM for up to 240 additional weeks. Adverse events recorded in this group occurred during the Open-Label Phase. All participants received fixed-dose open-label SIM 700 mg intravenous infusions every 2 weeks for up to 240 weeks.
Nervous system disorders Altered state of consciousness	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Blood and lymphatic system disorders Bandaemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Cardiac disorders Acute myocardial infarction	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Cardiac disorders Atrioventricular block second degree	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Cardiac disorders Bradycardia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Cardiac disorders Cardiac failure	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Cardiac disorders Coronary artery stenosis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Endocrine disorders Basedow's disease	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Endocrine disorders Hyperparathyroidism	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal discomfort	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal hernia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal pain	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal pain upper	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Ascites	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Colitis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Constipation	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Diverticulum	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Epiploic appendagitis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastritis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Haematemesis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Haematochezia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Hernial eventration	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Ileus	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Nausea	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Oesophageal varices haemorrhage	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Pancreatitis	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Umbilical hernia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Varices oesophageal	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Vomiting	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Asthenia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Chest pain	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Fatigue	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Multiple organ dysfunction syndrome	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Non-cardiac chest pain	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Oedema peripheral	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Peripheral swelling	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Pyrexia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Systemic inflammatory response syndrome	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Cholangitis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Gallbladder polyp	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Haemobilia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Ischaemic hepatitis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Immune system disorders Anaphylactic reaction	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Abscess limb	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Bacteraemia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Bacterial pyelonephritis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Bronchitis	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Cellulitis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Diverticulitis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Escherichia bacteraemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Escherichia sepsis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Escherichia urinary tract infection	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Gastroenteritis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Gastroenteritis bacterial	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Kidney infection	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Pneumonia	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Pyelonephritis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Rocky mountain spotted fever	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Sepsis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Urinary tract infection	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Viral infection	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Concussion	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Laceration	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Lumbar vertebral fracture	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Post procedural discomfort	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Post procedural haematoma	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Procedural hypotension	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Procedural pain	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Subarachnoid haemorrhage	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Blood osmolarity decreased	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Electrocardiogram T wave peaked	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Model for end stage liver disease score abnormal	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Model for end stage liver disease score increased	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hyperglycaemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hypokalaemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hyponatraemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Lactic acidosis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Back pain	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Compartment syndrome	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Myositis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Cervical myelopathy	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Dizziness	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Hepatic encephalopathy	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.5% 5/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Hypoaesthesia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Migraine with aura	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Nerve compression	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Somnolence	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Syncope	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Temporal lobe epilepsy	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Anxiety	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Bipolar disorder	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Drug abuse	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Major depression	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Mental status changes	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Psychiatric decompensation	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Psychotic disorder	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Suicidal ideation	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Acute kidney injury	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Dysuria	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Nephrolithiasis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Renal failure	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Ureterolithiasis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Asthma	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Hepatic hydrothorax	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Portopulmonary hypertension	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Respiratory depression	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Vascular disorders Haematoma	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Vascular disorders Hypotension	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Vascular disorders Orthostatic hypotension	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.

Other adverse events

Measure	Blinded Phase: SIM 200 mg n=87 participants at risk Adverse events recorded in this group occurred during the Blinded Phase. Participants received SIM 200 mg administered via intravenous infusion every 2 weeks for up to 240 weeks.	Blinded Phase: SIM 700 mg n=86 participants at risk Adverse events recorded in this group occurred during the Blinded Phase. Participants received SIM 700 mg administered via intravenous infusion every 2 weeks for up to 240 weeks.	Blinded Phase: Placebo n=85 participants at risk Adverse events recorded in this group occurred during the Blinded Phase. Participants received placebo to match SIM administered via intravenous infusion every 2 weeks for up to 240 weeks.	Open-Label Phase: SIM 700 mg n=40 participants at risk All participants who completed the randomized phase through the Week 240 visit, or who had an adjudicated clinical event prior to completing the randomized phase, were offered the opportunity to receive open-label SIM for up to 240 additional weeks. Adverse events recorded in this group occurred during the Open-Label Phase. All participants received fixed-dose open-label SIM 700 mg intravenous infusions every 2 weeks for up to 240 weeks.
Blood and lymphatic system disorders Anaemia	11.5% 10/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Blood and lymphatic system disorders Splenomegaly	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Cardiac disorders Palpitations	6.9% 6/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Ear and labyrinth disorders Vertigo	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal distension	10.3% 9/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	11.6% 10/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.6% 9/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.0% 4/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal pain	21.8% 19/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	26.7% 23/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	16.5% 14/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.5% 5/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal pain lower	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Abdominal pain upper	17.2% 15/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	22.1% 19/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.3% 13/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.5% 5/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Ascites	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.3% 8/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.6% 9/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	17.5% 7/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Constipation	10.3% 9/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	17.4% 15/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	11.8% 10/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Diarrhoea	27.6% 24/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	26.7% 23/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	38.8% 33/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	17.5% 7/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Haemorrhoids	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Nausea	33.3% 29/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	32.6% 28/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	32.9% 28/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	22.5% 9/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Portal hypertensive gastropathy	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.4% 8/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Umbilical hernia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Varices oesophageal	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	11.6% 10/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.4% 8/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Gastrointestinal disorders Vomiting	14.9% 13/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	17.4% 15/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	22.4% 19/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.0% 6/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Asthenia	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.8% 5/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Chest pain	9.2% 8/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	11.6% 10/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Chills	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.8% 5/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Fatigue	39.1% 34/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	37.2% 32/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	32.9% 28/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.0% 6/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Infusion site pain	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Oedema peripheral	14.9% 13/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	16.3% 14/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	18.8% 16/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.0% 6/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Pain	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Peripheral swelling	9.2% 8/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
General disorders Pyrexia	11.5% 10/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.5% 9/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Cholelithiasis	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.2% 7/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Hepatomegaly	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.2% 7/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Hepatobiliary disorders Jaundice	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Bronchitis	16.1% 14/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	16.3% 14/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	17.6% 15/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Gastroenteritis	6.9% 6/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Gastroenteritis viral	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Herpes zoster	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Influenza	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.4% 8/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Localised infection	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Nasopharyngitis	17.2% 15/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	18.6% 16/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	22.4% 19/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Peritonitis bacterial	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Pneumonia	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.8% 5/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Sinusitis	16.1% 14/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	18.6% 16/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	20.0% 17/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Upper respiratory tract infection	17.2% 15/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	22.1% 19/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.9% 11/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Infections and infestations Urinary tract infection	10.3% 9/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	16.3% 14/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	21.2% 18/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Contusion	11.5% 10/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	18.8% 16/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.5% 5/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Fall	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.8% 5/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.3% 13/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.0% 4/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Infusion related reaction	11.5% 10/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.9% 11/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Ligament sprain	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Muscle strain	5.7% 5/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Procedural pain	9.2% 8/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.2% 7/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Road traffic accident	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Injury, poisoning and procedural complications Skin abrasion	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Blood creatinine increased	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Blood glucose increased	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Investigations Weight increased	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Decreased appetite	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.9% 11/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hyperglycaemia	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	11.6% 10/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hyperkalaemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hypokalaemia	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.0% 4/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Metabolism and nutrition disorders Hyponatraemia	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.0% 4/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Arthralgia	19.5% 17/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	22.1% 19/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.3% 13/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Back pain	31.0% 27/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	20.9% 18/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	14.1% 12/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Flank pain	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.8% 5/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Joint swelling	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	18.4% 16/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.1% 13/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	11.8% 10/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.5% 5/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.5% 10/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.2% 7/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Myalgia	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.3% 2/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.4% 8/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Neck pain	9.2% 8/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	12.6% 11/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.5% 9/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.6% 9/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Dizziness	16.1% 14/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.3% 8/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.6% 9/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Headache	29.9% 26/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	32.6% 28/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	20.0% 17/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.5% 5/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Hepatic encephalopathy	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.0% 4/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Syncope	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Nervous system disorders Tremor	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.9% 5/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Anxiety	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Depression	4.6% 4/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Psychiatric disorders Insomnia	8.0% 7/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.8% 5/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.6% 9/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Chronic kidney disease	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Dysuria	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Renal and urinary disorders Pollakiuria	1.1% 1/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Reproductive system and breast disorders Gynaecomastia	2.3% 2/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Cough	18.4% 16/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	14.0% 12/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	15.3% 13/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.3% 9/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.0% 6/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	4.7% 4/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.3% 9/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.5% 9/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.2% 7/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.6% 11/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	9.3% 8/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	10.6% 9/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	1.2% 1/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	5.0% 2/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Skin and subcutaneous tissue disorders Alopecia	3.4% 3/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	8.1% 7/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Skin and subcutaneous tissue disorders Dry skin	6.9% 6/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.5% 1/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Skin and subcutaneous tissue disorders Pruritus	10.3% 9/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.8% 11/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.1% 6/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	7.5% 3/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Skin and subcutaneous tissue disorders Rash	9.2% 8/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	12.8% 11/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	17.6% 15/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.
Vascular disorders Hypertension	6.9% 6/87 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	3.5% 3/86 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	2.4% 2/85 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label study drug.	0.00% 0/40 • Baseline up to the last dose date plus 30 days (average exposure: SIM 200 mg= 109.3 weeks, SIM 700 mg= 115.9 weeks, Placebo= 120.2 weeks, Open-label SIM 700 mg= 46.2 weeks) Safety Analysis Set included all enrolled participants who were randomized and received at least one dose of study drug and Open-Label Safety Analysis Set included all participants who rolled over into the open-label phase and received at least 1 dose of open-label 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