Trial Outcomes & Findings for Emricasan, an Oral Caspase Inhibitor, in Subjects With NASH Cirrhosis and Severe Portal Hypertension (NCT NCT02960204)

NCT ID: NCT02960204

Last Updated: 2022-02-11

Results Overview

To assess the mean change from baseline to Week 24 in hepatic venous pressure gradient (HVPG)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

263 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2022-02-11

Participant Flow

Enrolled participants were excluded from the study and not randomized if they withdrew consent or did not meet inclusion/exclusion criteria.

Participant milestones

Participant milestones
Measure	Emricasan (5 mg) Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Overall Study STARTED	65	65	66	67
Overall Study Randomized	65	65	66	67
Overall Study Completed Week 24 of Study	62	62	60	66
Overall Study Completed Week 48 of Study	55	55	50	59
Overall Study COMPLETED	36	44	37	38
Overall Study NOT COMPLETED	29	21	29	29

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Emricasan (5 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=66 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=67 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo	Total n=263 Participants Total of all reporting groups
Region of Enrollment France	5 participants n=65 Participants	3 participants n=65 Participants	4 participants n=66 Participants	2 participants n=67 Participants	14 participants n=263 Participants
Region of Enrollment Switzerland	2 participants n=65 Participants	4 participants n=65 Participants	0 participants n=66 Participants	3 participants n=67 Participants	9 participants n=263 Participants
Age, Categorical <=18 years	0 Participants n=65 Participants	0 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	0 Participants n=263 Participants
Age, Categorical Between 18 and 65 years	47 Participants n=65 Participants	39 Participants n=65 Participants	41 Participants n=66 Participants	44 Participants n=67 Participants	171 Participants n=263 Participants
Age, Categorical >=65 years	18 Participants n=65 Participants	26 Participants n=65 Participants	25 Participants n=66 Participants	23 Participants n=67 Participants	92 Participants n=263 Participants
Age, Continuous	60.6 years STANDARD_DEVIATION 8.77 • n=65 Participants	62.0 years STANDARD_DEVIATION 8.81 • n=65 Participants	59.5 years STANDARD_DEVIATION 9.48 • n=66 Participants	61.4 years STANDARD_DEVIATION 7.90 • n=67 Participants	60.8 years STANDARD_DEVIATION 8.76 • n=263 Participants
Sex: Female, Male Female	37 Participants n=65 Participants	35 Participants n=65 Participants	33 Participants n=66 Participants	45 Participants n=67 Participants	150 Participants n=263 Participants
Sex: Female, Male Male	28 Participants n=65 Participants	30 Participants n=65 Participants	33 Participants n=66 Participants	22 Participants n=67 Participants	113 Participants n=263 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=65 Participants	11 Participants n=65 Participants	12 Participants n=66 Participants	18 Participants n=67 Participants	60 Participants n=263 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=65 Participants	50 Participants n=65 Participants	52 Participants n=66 Participants	47 Participants n=67 Participants	191 Participants n=263 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=65 Participants	4 Participants n=65 Participants	2 Participants n=66 Participants	2 Participants n=67 Participants	12 Participants n=263 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=65 Participants	0 Participants n=65 Participants	1 Participants n=66 Participants	0 Participants n=67 Participants	1 Participants n=263 Participants
Race (NIH/OMB) Asian	0 Participants n=65 Participants	2 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	2 Participants n=263 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=65 Participants	0 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	0 Participants n=263 Participants
Race (NIH/OMB) Black or African American	0 Participants n=65 Participants	0 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	0 Participants n=263 Participants
Race (NIH/OMB) White	58 Participants n=65 Participants	58 Participants n=65 Participants	60 Participants n=66 Participants	64 Participants n=67 Participants	240 Participants n=263 Participants
Race (NIH/OMB) More than one race	0 Participants n=65 Participants	0 Participants n=65 Participants	1 Participants n=66 Participants	0 Participants n=67 Participants	1 Participants n=263 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=65 Participants	5 Participants n=65 Participants	4 Participants n=66 Participants	3 Participants n=67 Participants	19 Participants n=263 Participants
Region of Enrollment United States	51 participants n=65 Participants	50 participants n=65 Participants	57 participants n=66 Participants	54 participants n=67 Participants	212 participants n=263 Participants
Region of Enrollment Germany	3 participants n=65 Participants	1 participants n=65 Participants	1 participants n=66 Participants	3 participants n=67 Participants	7 participants n=263 Participants
Region of Enrollment Spain	4 participants n=65 Participants	7 participants n=65 Participants	4 participants n=66 Participants	5 participants n=67 Participants	20 participants n=263 Participants
Hepatic Venous Pressure Gradient	16.88 mmHg STANDARD_DEVIATION 3.573 • n=65 Participants	17.25 mmHg STANDARD_DEVIATION 3.300 • n=65 Participants	16.91 mmHg STANDARD_DEVIATION 3.545 • n=66 Participants	16.81 mmHg STANDARD_DEVIATION 3.724 • n=67 Participants	16.96 mmHg STANDARD_DEVIATION 3.586 • n=263 Participants
Taking Non-Selective Beta Blockers at Baseline No	37 Participants n=65 Participants	39 Participants n=65 Participants	40 Participants n=66 Participants	40 Participants n=67 Participants	156 Participants n=263 Participants
Taking Non-Selective Beta Blockers at Baseline Yes	28 Participants n=65 Participants	26 Participants n=65 Participants	26 Participants n=66 Participants	27 Participants n=67 Participants	107 Participants n=263 Participants
Cirrhosis Baseline Status Compensated Cirrhosis	49 Participants n=65 Participants	49 Participants n=65 Participants	48 Participants n=66 Participants	55 Participants n=67 Participants	201 Participants n=263 Participants
Cirrhosis Baseline Status Decompensated Cirrhosis	16 Participants n=65 Participants	16 Participants n=65 Participants	18 Participants n=66 Participants	12 Participants n=67 Participants	62 Participants n=263 Participants
Varices None	19 Participants n=65 Participants	14 Participants n=65 Participants	19 Participants n=66 Participants	19 Participants n=67 Participants	71 Participants n=263 Participants
Varices Present - Small	21 Participants n=65 Participants	27 Participants n=65 Participants	25 Participants n=66 Participants	34 Participants n=67 Participants	107 Participants n=263 Participants
Varices Present - Medium	21 Participants n=65 Participants	16 Participants n=65 Participants	14 Participants n=66 Participants	6 Participants n=67 Participants	57 Participants n=263 Participants
Varices Present - Large	4 Participants n=65 Participants	7 Participants n=65 Participants	8 Participants n=66 Participants	7 Participants n=67 Participants	26 Participants n=263 Participants
Varices Present - Not Specified	0 Participants n=65 Participants	1 Participants n=65 Participants	0 Participants n=66 Participants	1 Participants n=67 Participants	2 Participants n=263 Participants
Compensated Status with Varices Compensated with none/small varices	32 Participants n=65 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	29 Participants n=64 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	32 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	42 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	135 Participants n=261 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.
Compensated Status with Varices Compensated with medium/large varices	17 Participants n=65 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	19 Participants n=64 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	16 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	12 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	64 Participants n=261 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.
Compensated Status with Varices Decompensated with none/small varices	8 Participants n=65 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	12 Participants n=64 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	12 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	11 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	43 Participants n=261 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.
Compensated Status with Varices Decompensated with medium/large varices	8 Participants n=65 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	4 Participants n=64 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	6 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	1 Participants n=66 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.	19 Participants n=261 Participants • Two subjects (one in 25 mg emricasan arm and one in placebo arm) did not have data available.
Model for End-Stage Liver Disease (MELD) Score	9.17 units on a scale STANDARD_DEVIATION 2.673 • n=65 Participants	9.06 units on a scale STANDARD_DEVIATION 2.200 • n=65 Participants	9.24 units on a scale STANDARD_DEVIATION 2.512 • n=66 Participants	8.40 units on a scale STANDARD_DEVIATION 2.511 • n=67 Participants	8.97 units on a scale STANDARD_DEVIATION 2.489 • n=263 Participants
MELD Classification (Median Cut) <= 8	33 Participants n=65 Participants	31 Participants n=65 Participants	30 Participants n=66 Participants	44 Participants n=67 Participants	138 Participants n=263 Participants
MELD Classification (Median Cut) >= 9	32 Participants n=65 Participants	34 Participants n=65 Participants	36 Participants n=66 Participants	23 Participants n=67 Participants	125 Participants n=263 Participants
MELD Component: Total Bilirubin	1.27 mg/dL STANDARD_DEVIATION 0.514 • n=65 Participants	1.31 mg/dL STANDARD_DEVIATION 0.482 • n=65 Participants	1.39 mg/dL STANDARD_DEVIATION 0.725 • n=66 Participants	1.20 mg/dL STANDARD_DEVIATION 0.600 • n=67 Participants	1.29 mg/dL STANDARD_DEVIATION 0.696 • n=263 Participants
MELD Component: Serum Creatine	1.02 mg/dL STANDARD_DEVIATION 0.079 • n=65 Participants	1.01 mg/dL STANDARD_DEVIATION 0.053 • n=65 Participants	1.04 mg/dL STANDARD_DEVIATION 0.160 • n=66 Participants	1.02 mg/dL STANDARD_DEVIATION 0.086 • n=67 Participants	1.02 mg/dL STANDARD_DEVIATION 0.102 • n=263 Participants
MELD Component: International Normalized Ratio	1.18 mg/dL STANDARD_DEVIATION 0.167 • n=65 Participants	1.16 mg/dL STANDARD_DEVIATION 0.167 • n=65 Participants	1.16 mg/dL STANDARD_DEVIATION 0.115 • n=66 Participants	1.14 mg/dL STANDARD_DEVIATION 0.113 • n=67 Participants	1.16 mg/dL STANDARD_DEVIATION 0.128 • n=263 Participants
Child-Pugh Score	5.5 units on a scale STANDARD_DEVIATION 0.96 • n=65 Participants	5.5 units on a scale STANDARD_DEVIATION 0.69 • n=65 Participants	5.6 units on a scale STANDARD_DEVIATION 0.86 • n=66 Participants	5.4 units on a scale STANDARD_DEVIATION 0.75 • n=67 Participants	5.5 units on a scale STANDARD_DEVIATION 0.82 • n=263 Participants
Child-Pugh Classification A	56 Participants n=64 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	59 Participants n=64 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	55 Participants n=66 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	61 Participants n=67 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	231 Participants n=261 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.
Child-Pugh Classification B	7 Participants n=64 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	5 Participants n=64 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	11 Participants n=66 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	6 Participants n=67 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	29 Participants n=261 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.
Child-Pugh Classification C	1 Participants n=64 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	0 Participants n=64 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	0 Participants n=66 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	0 Participants n=67 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.	1 Participants n=261 Participants • Two subjects (one in the 5 mg emricasan arm and one in the 25 mg emricasan arm) did not have data available.
Child-Pugh Component: Total Bilirubin 1	58 Participants n=65 Participants	61 Participants n=65 Participants	59 Participants n=66 Participants	64 Participants n=67 Participants	242 Participants n=263 Participants
Child-Pugh Component: Total Bilirubin 2	5 Participants n=65 Participants	3 Participants n=65 Participants	4 Participants n=66 Participants	2 Participants n=67 Participants	14 Participants n=263 Participants
Child-Pugh Component: Total Bilirubin 3	2 Participants n=65 Participants	1 Participants n=65 Participants	3 Participants n=66 Participants	1 Participants n=67 Participants	7 Participants n=263 Participants
Child-Pugh Component: Total Albumin 1	49 Participants n=65 Participants	52 Participants n=65 Participants	51 Participants n=66 Participants	57 Participants n=67 Participants	209 Participants n=263 Participants
Child-Pugh Component: Total Albumin 2	15 Participants n=65 Participants	13 Participants n=65 Participants	14 Participants n=66 Participants	10 Participants n=67 Participants	52 Participants n=263 Participants
Child-Pugh Component: Total Albumin 3	1 Participants n=65 Participants	0 Participants n=65 Participants	1 Participants n=66 Participants	0 Participants n=67 Participants	2 Participants n=263 Participants
Child-Pugh Component: Ascites 1	58 Participants n=65 Participants	61 Participants n=65 Participants	57 Participants n=66 Participants	62 Participants n=67 Participants	238 Participants n=263 Participants
Child-Pugh Component: Ascites 2	7 Participants n=65 Participants	4 Participants n=65 Participants	9 Participants n=66 Participants	5 Participants n=67 Participants	25 Participants n=263 Participants
Child-Pugh Component: Ascites 3	0 Participants n=65 Participants	0 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	0 Participants n=263 Participants
Child-Pugh Component Hepatic Encephalopathy 1	63 Participants n=65 Participants	65 Participants n=65 Participants	66 Participants n=66 Participants	67 Participants n=67 Participants	261 Participants n=263 Participants
Child-Pugh Component Hepatic Encephalopathy 2	2 Participants n=65 Participants	0 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	2 Participants n=263 Participants
Child-Pugh Component Hepatic Encephalopathy 3	0 Participants n=65 Participants	0 Participants n=65 Participants	0 Participants n=66 Participants	0 Participants n=67 Participants	0 Participants n=263 Participants
Child-Pugh Component: Prothrombin Time (or International Normalized Ratio) 1	63 Participants n=64 Participants • One subject in the 5 mg emricasan arm did not have data available.	65 Participants n=65 Participants • One subject in the 5 mg emricasan arm did not have data available.	66 Participants n=66 Participants • One subject in the 5 mg emricasan arm did not have data available.	67 Participants n=67 Participants • One subject in the 5 mg emricasan arm did not have data available.	261 Participants n=262 Participants • One subject in the 5 mg emricasan arm did not have data available.
Child-Pugh Component: Prothrombin Time (or International Normalized Ratio) 2	1 Participants n=64 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=65 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=66 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=67 Participants • One subject in the 5 mg emricasan arm did not have data available.	1 Participants n=262 Participants • One subject in the 5 mg emricasan arm did not have data available.
Child-Pugh Component: Prothrombin Time (or International Normalized Ratio) 3	0 Participants n=64 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=65 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=66 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=67 Participants • One subject in the 5 mg emricasan arm did not have data available.	0 Participants n=262 Participants • One subject in the 5 mg emricasan arm did not have data available.
Gallstones	30 Participants n=65 Participants	28 Participants n=65 Participants	31 Participants n=66 Participants	27 Participants n=67 Participants	116 Participants n=263 Participants
Cholecystectomy	24 Participants n=65 Participants	16 Participants n=65 Participants	20 Participants n=66 Participants	26 Participants n=67 Participants	86 Participants n=263 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: Full analysis set (Multiple Imputation)

To assess the mean change from baseline to Week 24 in hepatic venous pressure gradient (HVPG)

Outcome measures

Outcome measures
Measure	Emricasan (5 mg) n=61 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=62 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=56 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=64 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Mean Change in Hepatic Venous Pressure Gradient (HVPG)	-0.48 mmHg Standard Deviation 3.356	-0.81 mmHg Standard Deviation 3.669	-0.70 mmHg Standard Deviation 3.400	-0.18 mmHg Standard Deviation 3.028

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Full Analysis Set

To assess subjects who have at least a 20 percent reduction from baseline in HVPG

Outcome measures

Outcome measures
Measure	Emricasan (5 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=66 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=67 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Improvement of HVPG Response Using a 20% Reduction From Baseline >= 20% reduction in HVPG: Yes	8 participants	14 participants	10 participants	9 participants
Improvement of HVPG Response Using a 20% Reduction From Baseline >= 20% Reduction in HVPG: No	53 participants	48 participants	46 participants	55 participants
Improvement of HVPG Response Using a 20% Reduction From Baseline Unknown	4 participants	3 participants	10 participants	3 participants

SECONDARY outcome

Timeframe: Baseline to Week 24, Baseline to Week 48

Population: Full Analysis Set (Observed Cases)

To assess whether number of Caspase 3/7 biomarkers is affected by emricasan as compared to placebo

Outcome measures

Outcome measures
Measure	Emricasan (5 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=66 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=67 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Caspase 3/7 Week 24	-0.01 RLU Standard Deviation 0.475	-0.40 RLU Standard Deviation 0.597	-0.46 RLU Standard Deviation 0.663	-0.04 RLU Standard Deviation 0.339
Caspase 3/7 Week 48	0.13 RLU Standard Deviation 0.541	-0.18 RLU Standard Deviation 0.665	-0.48 RLU Standard Deviation 0.564	0.05 RLU Standard Deviation 0.373

SECONDARY outcome

Timeframe: Baseline to Week 24 and Baseline to Week 48

Population: Full Analysis Set (Observed Cases)

To assess whether amount of non-specific (ALT) biomarkers are affected by emricasan compared to placebo

Outcome measures

Outcome measures
Measure	Emricasan (5 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=65 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=66 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=67 Participants Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Alanine Aminotransferase (ALT) Week 24	-7.83 U/L Standard Deviation 10.650	-8.06 U/L Standard Deviation 10.542	-7.06 U/L Standard Deviation 12.010	-1.69 U/L Standard Deviation 12.907
Alanine Aminotransferase (ALT) Week 48	-6.54 U/L Standard Deviation 11.917	-4.16 U/L Standard Deviation 9.850	-5.34 U/L Standard Deviation 11.153	-2.97 U/L Standard Deviation 12.457

Adverse Events

Emricasan (5 mg)

Serious events: 15 serious events

Other events: 59 other events

Deaths: 1 deaths

Emricasan (25 mg)

Serious events: 23 serious events

Other events: 62 other events

Deaths: 2 deaths

Emricasan (50 mg)

Serious events: 21 serious events

Other events: 57 other events

Deaths: 1 deaths

Matching Placebo

Serious events: 16 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mark Hubka, Executive Director, Medical Affairs

Histogen Inc.

Phone: 858-526-3109

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication or discussion must be approved by the Sponsor prior to release.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Emricasan (5 mg) n=65 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=65 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=66 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=67 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Gastrointestinal disorders Gastrointestinal disorders	9.2% 6/65 • Number of events 6 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.2% 6/65 • Number of events 6 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • Number of events 3 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Infections and infestations	6.2% 4/65 • Number of events 4 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.8% 7/65 • Number of events 7 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.6% 7/66 • Number of events 7 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • Number of events 3 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms	1.5% 1/65 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.6% 3/65 • Number of events 3 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Respiratory disorders	1.5% 1/65 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Renal and urinary disorders Renal disorders	1.5% 1/65 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Cardiac disorders Cardiac disorders	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Blood and lymphatic system disorders Blood disorders	1.5% 1/65 • Number of events 1 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Multi-organ failure	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Acute hepatic failure	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Nervous system disorders Hepatic encephalopathy	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Injury, poisoning and procedural complications Tibial fracture	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • Number of events 2 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Blood and lymphatic system disorders Anemia	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Blood and lymphatic system disorders Coombs positive haemolytic anaemia	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Blood and lymphatic system disorders Splenic vein thrombosis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Cardiac disorders Acute myocardial infarction	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Cardiac disorders Atrial fibrillation	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Cardiac disorders Cardiac failure congestive	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Eye disorders Vitreous haemorrhage	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Ascites	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Haemorrhoidal haemorrhage	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Oesophagael varices haemorrhage	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Death	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Localised oedema	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Non-cardiac chest pain	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Oedema peripheral	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Pyrexia	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Biliary colic	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Cholecytitis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Granulomatous liver disease	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Hepatic failure	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Hepatorenal syndrome	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Bacterial pyelonephritis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Bronchitis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Cellulitis	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Cystitis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

Other adverse events
Measure	Emricasan (5 mg) n=65 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. Emricasan	Emricasan (25 mg) n=65 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. Emricasan	Emricasan (50 mg) n=66 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. Emricasan	Matching Placebo n=67 participants at risk Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. Placebo
Gastrointestinal disorders Gastrointestinal disorders	47.7% 31/65 • Number of events 31 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	58.5% 38/65 • Number of events 38 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	50.0% 33/66 • Number of events 33 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	58.2% 39/67 • Number of events 39 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Pneumonia	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	6.2% 4/65 • Number of events 4 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.2% 6/65 • Number of events 6 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • Number of events 3 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.0% 4/67 • Number of events 4 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Nervous system disorders Hepatic encephalopathy	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.6% 5/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	17.9% 12/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Renal and urinary disorders Acute kidney injury	15.4% 10/65 • Number of events 10 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	15.4% 10/65 • Number of events 10 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	15.2% 10/66 • Number of events 10 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	14.9% 10/67 • Number of events 10 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Blood and lymphatic system disorders Anaemia	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.6% 7/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	14.9% 10/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Abdominal distension	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.0% 4/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Abdominal pain	10.8% 7/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.6% 5/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.4% 7/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Abdominal pain upper	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.8% 7/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	12.1% 8/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Ascites	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	13.8% 9/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.1% 4/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	11.9% 8/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Constipation	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.0% 6/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Diarrhea	15.4% 10/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.8% 7/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.1% 6/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	19.4% 13/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Nausea	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	13.8% 9/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	12.1% 8/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	16.4% 11/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Esophageal varices hemorrhage	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Gastrointestinal disorders Vomiting	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.0% 4/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Asthenia	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.1% 4/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Fatigue	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.1% 6/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.0% 6/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Edema peripheral	13.8% 9/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	21.5% 14/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	12.1% 8/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	11.9% 8/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
General disorders Pyrexia	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Hyperbilirubinemia	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.0% 4/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Hepatobiliary disorders Portal vein thrombosis	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.5% 5/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Bronchitis	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.6% 7/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Cellulitis	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.1% 4/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.0% 4/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Influenza	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Nasopharyngitis	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.1% 4/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.5% 5/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Sinusitis	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.0% 4/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Upper respiratory infection	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.1% 4/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.5% 5/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Infections and infestations Urinary tract infection	13.8% 9/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	16.9% 11/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.1% 6/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	14.9% 10/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Injury, poisoning and procedural complications Fall	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.0% 6/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Metabolism and nutrition disorders Diabetes mellitus	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.5% 5/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Musculoskeletal and connective tissue disorders Back pain	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	11.9% 8/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Musculoskeletal and connective tissue disorders Muscle spasms	10.8% 7/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.6% 5/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Nervous system disorders Dizziness	6.2% 4/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	6.1% 4/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	9.0% 6/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Nervous system disorders Headache	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.8% 7/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	10.6% 7/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.5% 5/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Psychiatric disorders Anxiety	7.7% 5/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.5% 3/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Psychiatric disorders Insomnia	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	4.6% 3/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.2% 6/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.5% 5/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Skin and subcutaneous tissue disorders Pruritus	3.1% 2/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	1.5% 1/65 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	7.6% 5/66 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.	3.0% 2/67 • First day of study treatment through the follow-up phase (Week 28 for participants who received treatment through Week 24 OR Week 50 for participants who received treatment through Week 48). Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.