Trial Outcomes & Findings for Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (NCT NCT04065841)

NCT ID: NCT04065841

Last Updated: 2025-01-28

Results Overview

Response was defined as at least a one-stage improvement in fibrosis without worsening of nonalcoholic steatohepatitis (NASH) Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 234 participants
• Primary outcome timeframe: Baseline, Week 48
• Results posted on: 2025-01-28

Participant Flow

234 participants were randomized at 81 sites.

One of the randomized participants in the tropifexor group was not treated due to loss of interest in the study.

Participant milestones

Measure	Tropifexor Monotherapy Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Overall Study STARTED	54	55	84	41
Overall Study COMPLETED	25	33	42	21
Overall Study NOT COMPLETED	29	22	42	20

Reasons for withdrawal

Measure	Tropifexor Monotherapy Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Overall Study Adverse Event	4	2	10	1
Overall Study Lost to Follow-up	1	2	2	2
Overall Study Physician Decision	1	0	0	0
Overall Study Protocol Violation	0	1	0	0
Overall Study Study terminated by Sponsor	22	16	28	17
Overall Study Withdrawal by Subject	1	1	2	0

Baseline Characteristics

Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis.

Baseline characteristics by cohort

Measure	Tropifexor Monotherapy n=53 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=55 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=84 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=41 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily	Total n=233 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	42 Participants n=5 Participants	39 Participants n=7 Participants	70 Participants n=5 Participants	35 Participants n=4 Participants	186 Participants n=21 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	16 Participants n=7 Participants	14 Participants n=5 Participants	6 Participants n=4 Participants	47 Participants n=21 Participants
Age, Continuous	54.5 Years STANDARD_DEVIATION 11.09 • n=5 Participants	56.0 Years STANDARD_DEVIATION 12.13 • n=7 Participants	54.7 Years STANDARD_DEVIATION 10.82 • n=5 Participants	54.9 Years STANDARD_DEVIATION 10.22 • n=4 Participants	55.0 Years STANDARD_DEVIATION 11.05 • n=21 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	34 Participants n=7 Participants	43 Participants n=5 Participants	26 Participants n=4 Participants	129 Participants n=21 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants	15 Participants n=4 Participants	104 Participants n=21 Participants
Race/Ethnicity, Customized White	39 Participants n=5 Participants	40 Participants n=7 Participants	63 Participants n=5 Participants	32 Participants n=4 Participants	174 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	7 Participants n=21 Participants
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants	5 Participants n=4 Participants	41 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: Full Analysis Set (FAS): all participants to whom study treatment has been assigned by randomization and had an assessment of response at Week 48. Efficacy analysis was conducted using the FAS.

Response was defined as at least a one-stage improvement in fibrosis without worsening of nonalcoholic steatohepatitis (NASH)

Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.

Outcome measures

Measure	Tropifexor Monotherapy n=23 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=28 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=34 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=17 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Histological Improvement: Number and Percentage of Participants Who Responded at Week 48 Compared With Baseline	6 Participants	9 Participants	10 Participants	4 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: Full Analysis Set (FAS): all participants to whom study treatment has been assigned by randomization. Efficacy analysis was conducted using the FAS

Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.

Outcome measures

Measure	Tropifexor Monotherapy n=23 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=28 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=34 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=17 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Number and Percentage of Participants With Resolution of NASH and no Worsening of Fibrosis	5 Participants	3 Participants	10 Participants	2 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.

Outcome measures

Measure	Tropifexor Monotherapy n=23 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=28 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=34 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=17 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Number and Percentage of Participants Who Achieved Resolution of NASH and no Worsening of Fibrosis OR Improvement in Fibrosis by at Least One Stage Without Worsening of NASH	8 Participants	10 Participants	14 Participants	5 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.

Outcome measures

Measure	Tropifexor Monotherapy n=23 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=28 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=34 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=17 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Number and Percentage of Participants With at Least One Stage Improvement in Fibrosis	6 Participants	10 Participants	11 Participants	4 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

Fibrosis staging and Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.

Outcome measures

Measure	Tropifexor Monotherapy n=23 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=28 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=34 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=17 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Number and Percentage of Participants With at Least Two Stage Improvement in Fibrosis Without Worsening of NASH	3 Participants	4 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: Data are reported for the total number of participants in the treatment group with response variable defined.

Whether the participants had 5% or more reduction in body weight.

Outcome measures

Measure	Tropifexor Monotherapy n=23 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=32 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=35 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=24 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Number and Percentage of Participants Achieving 5% or More Reduction in Body Weight at Week 48 Compared With Baseline	12 Participants	9 Participants	28 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: FAS: all participants to whom study treatment has been assigned by randomization and had an assessment at Week 48. This analysis was performed in 40% of participants.

Change in liver fat content based on MRI-PDFF.

Outcome measures

Measure	Tropifexor Monotherapy n=15 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=19 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=21 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=20 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Change From Baseline to Week 48 in Percent Liver Fat Content Based on Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI - PDFF)	-6.57 Percent liver fat Standard Deviation 5.913	-2.64 Percent liver fat Standard Deviation 5.866	-7.69 Percent liver fat Standard Deviation 6.702	-2.58 Percent liver fat Standard Deviation 3.599

SECONDARY outcome

Timeframe: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)

Population: The safety analysis set included all participants who received at least one dose of study treatment. At each time point, only participants with a value at both Baseline and that time point were included.

To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.

Outcome measures

Measure	Tropifexor Monotherapy n=53 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=55 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=84 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=41 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 2	-17.4 units per liter (U/L) Standard Deviation 28.30	-3.2 units per liter (U/L) Standard Deviation 15.52	-13.5 units per liter (U/L) Standard Deviation 24.47	-4.3 units per liter (U/L) Standard Deviation 18.94
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 4	-16.1 units per liter (U/L) Standard Deviation 18.41	-4.2 units per liter (U/L) Standard Deviation 19.84	-14.5 units per liter (U/L) Standard Deviation 25.78	-3.2 units per liter (U/L) Standard Deviation 17.81
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 8	-9.9 units per liter (U/L) Standard Deviation 20.02	-7.9 units per liter (U/L) Standard Deviation 19.82	-17.6 units per liter (U/L) Standard Deviation 23.47	-5.6 units per liter (U/L) Standard Deviation 19.67
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 12	-13.8 units per liter (U/L) Standard Deviation 28.48	-11.3 units per liter (U/L) Standard Deviation 16.57	-21.0 units per liter (U/L) Standard Deviation 24.91	-2.5 units per liter (U/L) Standard Deviation 25.05
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 16	-15.4 units per liter (U/L) Standard Deviation 26.94	-12.4 units per liter (U/L) Standard Deviation 20.38	-24.4 units per liter (U/L) Standard Deviation 26.13	-3.2 units per liter (U/L) Standard Deviation 24.57
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 20	-14.5 units per liter (U/L) Standard Deviation 27.92	-14.6 units per liter (U/L) Standard Deviation 24.96	-25.0 units per liter (U/L) Standard Deviation 28.95	-5.7 units per liter (U/L) Standard Deviation 20.20
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 24	-15.1 units per liter (U/L) Standard Deviation 28.34	-17.0 units per liter (U/L) Standard Deviation 22.43	-35.2 units per liter (U/L) Standard Deviation 30.61	-4.0 units per liter (U/L) Standard Deviation 28.28
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 32	-18.2 units per liter (U/L) Standard Deviation 30.97	-13.0 units per liter (U/L) Standard Deviation 28.01	-33.8 units per liter (U/L) Standard Deviation 37.21	-1.0 units per liter (U/L) Standard Deviation 41.32
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 40	-12.7 units per liter (U/L) Standard Deviation 39.35	-15.2 units per liter (U/L) Standard Deviation 26.91	-36.1 units per liter (U/L) Standard Deviation 27.42	-8.7 units per liter (U/L) Standard Deviation 40.70
Change From Baseline in Alanine Transaminase (ALT) Over Time Week 48	-11.7 units per liter (U/L) Standard Deviation 49.32	-12.0 units per liter (U/L) Standard Deviation 28.99	-36.9 units per liter (U/L) Standard Deviation 30.20	-19.5 units per liter (U/L) Standard Deviation 30.16
Change From Baseline in Alanine Transaminase (ALT) Over Time Follow-up	-1.5 units per liter (U/L) Standard Deviation 37.77	-9.4 units per liter (U/L) Standard Deviation 27.94	-17.0 units per liter (U/L) Standard Deviation 27.97	-8.8 units per liter (U/L) Standard Deviation 28.88

SECONDARY outcome

Timeframe: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)

Population: The safety analysis set included all participants who received at least one dose of study treatment. At each time point, only participants with a value at both Baseline and that time point were included.

To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.

Outcome measures

Measure	Tropifexor Monotherapy n=53 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=55 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=84 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=41 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 2	-7.9 U/L Standard Deviation 14.93	-3.9 U/L Standard Deviation 12.98	-5.5 U/L Standard Deviation 19.38	-1.8 U/L Standard Deviation 13.46
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 4	-1.7 U/L Standard Deviation 17.43	-2.4 U/L Standard Deviation 20.49	-4.9 U/L Standard Deviation 22.19	-2.2 U/L Standard Deviation 15.35
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 8	1.2 U/L Standard Deviation 23.71	-7.4 U/L Standard Deviation 14.12	-6.7 U/L Standard Deviation 20.13	-1.6 U/L Standard Deviation 15.19
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 12	0.4 U/L Standard Deviation 21.34	-10.3 U/L Standard Deviation 13.25	-10.4 U/L Standard Deviation 21.42	-1.4 U/L Standard Deviation 19.08
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 16	-0.7 U/L Standard Deviation 21.71	-10.8 U/L Standard Deviation 16.37	-12.9 U/L Standard Deviation 20.98	-2.4 U/L Standard Deviation 17.42
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 20	-1.0 U/L Standard Deviation 22.46	-10.0 U/L Standard Deviation 19.81	-10.8 U/L Standard Deviation 25.98	-3.9 U/L Standard Deviation 14.23
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 24	-1.4 U/L Standard Deviation 19.96	-13.8 U/L Standard Deviation 19.81	-18.3 U/L Standard Deviation 23.26	-2.2 U/L Standard Deviation 21.96
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 32	-2.0 U/L Standard Deviation 32.00	-11.2 U/L Standard Deviation 20.12	-15.4 U/L Standard Deviation 34.92	-1.1 U/L Standard Deviation 29.62
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 40	3.2 U/L Standard Deviation 34.40	-11.9 U/L Standard Deviation 20.22	-20.6 U/L Standard Deviation 22.57	-5.9 U/L Standard Deviation 23.21
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Week 48	-0.7 U/L Standard Deviation 31.34	-11.3 U/L Standard Deviation 23.53	-20.4 U/L Standard Deviation 24.19	-12.8 U/L Standard Deviation 17.01
Change From Baseline in Aspartate Aminotransferase (AST) Over Time Follow-up	-2.0 U/L Standard Deviation 21.21	-8.2 U/L Standard Deviation 24.01	-10.6 U/L Standard Deviation 21.27	-3.3 U/L Standard Deviation 23.64

SECONDARY outcome

Timeframe: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)

Population: The safety analysis set included all participants who received at least one dose of study treatment. At each time point, only participants with a value at both Baseline and that time point were included.

To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.

Outcome measures

Measure	Tropifexor Monotherapy n=53 Participants Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Licogliflozin Monotherapy n=55 Participants Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination Therapy n=84 Participants Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=41 Participants Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 2	-34.8 U/L Standard Deviation 46.06	-2.8 U/L Standard Deviation 21.81	-30.6 U/L Standard Deviation 45.85	3.8 U/L Standard Deviation 34.60
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 4	-43.6 U/L Standard Deviation 60.28	-7.0 U/L Standard Deviation 20.56	-41.7 U/L Standard Deviation 60.81	-1.1 U/L Standard Deviation 31.63
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 40	-38.8 U/L Standard Deviation 42.89	-20.6 U/L Standard Deviation 30.99	-50.0 U/L Standard Deviation 72.08	0.2 U/L Standard Deviation 54.04
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 48	-31.6 U/L Standard Deviation 46.00	-20.1 U/L Standard Deviation 29.10	-44.1 U/L Standard Deviation 67.27	-11.1 U/L Standard Deviation 38.01
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Follow-up	14.8 U/L Standard Deviation 69.63	-9.4 U/L Standard Deviation 42.96	5.6 U/L Standard Deviation 139.33	7.3 U/L Standard Deviation 43.69
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 8	-37.9 U/L Standard Deviation 37.85	-15.3 U/L Standard Deviation 28.06	-45.0 U/L Standard Deviation 69.45	-0.9 U/L Standard Deviation 33.16
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 12	-37.4 U/L Standard Deviation 96.36	-17.5 U/L Standard Deviation 33.83	-48.0 U/L Standard Deviation 76.04	5.2 U/L Standard Deviation 25.03
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 16	-39.4 U/L Standard Deviation 41.77	-15.5 U/L Standard Deviation 33.94	-52.2 U/L Standard Deviation 78.29	2.2 U/L Standard Deviation 36.71
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 20	-32.9 U/L Standard Deviation 37.55	-14.8 U/L Standard Deviation 41.11	-50.1 U/L Standard Deviation 79.30	-0.8 U/L Standard Deviation 45.84
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 24	-32.0 U/L Standard Deviation 45.55	-22.3 U/L Standard Deviation 28.06	-58.1 U/L Standard Deviation 82.45	3.3 U/L Standard Deviation 44.08
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time Week 32	-34.5 U/L Standard Deviation 37.31	-19.4 U/L Standard Deviation 28.68	-55.1 U/L Standard Deviation 76.85	8.2 U/L Standard Deviation 45.21

Adverse Events

LJN452

Serious events: 4 serious events

Other events: 35 other events

Deaths: 0 deaths

LIK066

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Combination

Serious events: 4 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

All Patients

Serious events: 14 serious events

Other events: 151 other events

Deaths: 0 deaths

Serious adverse events

Measure	LJN452 n=53 participants at risk Tropifexor monotherapy arm: tropifexor 140 mcgcapsule (+ placebo matching licogliflozin tablet), once daily orally	LIK066 n=55 participants at risk Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination n=84 participants at risk Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=41 participants at risk Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily	All Patients n=233 participants at risk All Patients
Blood and lymphatic system disorders Anaemia	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure chronic	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Haemoperitoneum	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Pancreatitis	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
General disorders Non-cardiac chest pain	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholecystitis	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Haemobilia	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations COVID-19 pneumonia	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.8% 1/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Hepatitis E	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.8% 1/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.8% 1/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.8% 1/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Sciatica	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Renal and urinary disorders Calculus urinary	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.43% 1/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.

Other adverse events

Measure	LJN452 n=53 participants at risk Tropifexor monotherapy arm: tropifexor 140 mcgcapsule (+ placebo matching licogliflozin tablet), once daily orally	LIK066 n=55 participants at risk Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Combination n=84 participants at risk Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Placebo n=41 participants at risk Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily	All Patients n=233 participants at risk All Patients
Gastrointestinal disorders Abdominal distension	3.8% 2/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.5% 3/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	6.0% 5/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.9% 2/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.2% 12/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	7.5% 4/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 2/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.4% 8/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	13.2% 7/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	38.2% 21/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	25.0% 21/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	14.6% 6/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	23.6% 55/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Dyspepsia	3.8% 2/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	7.3% 4/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 2/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.9% 9/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Flatulence	7.5% 4/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	7.3% 4/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 3/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.7% 11/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	11.3% 6/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	7.3% 4/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	8.3% 7/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.9% 2/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	8.2% 19/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	13.2% 7/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 2/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 3/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.9% 2/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	6.0% 14/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
General disorders Fatigue	5.7% 3/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.1% 5/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
General disorders Pyrexia	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	9.1% 5/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.6% 6/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations COVID-19	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	18.2% 10/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	10.7% 9/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	22.0% 9/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	12.4% 29/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	5.7% 3/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	10.9% 6/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 4/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.9% 2/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	6.4% 15/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Investigations Glucose urine present	3.8% 2/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.5% 3/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 2/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.0% 7/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Investigations Urine albumin/creatinine ratio increased	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 2/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 2/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	7.3% 3/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.4% 8/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	1.9% 1/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 2/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	7.3% 3/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.6% 6/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.5% 3/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 2/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 1/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.6% 6/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	5.7% 3/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 2/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.4% 2/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.0% 7/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Headache	3.8% 2/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.8% 1/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.6% 3/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	14.6% 6/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.2% 12/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Insomnia	7.5% 4/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.1% 5/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Renal and urinary disorders Haematuria	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.5% 3/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.3% 3/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Balanoposthitis	0.00% 0/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	7.3% 4/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	1.2% 1/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	2.1% 5/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	37.7% 20/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	16.4% 9/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	26.2% 22/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	9.8% 4/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	23.6% 55/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	3.8% 2/53 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	5.5% 3/55 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/84 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	4.9% 2/41 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.	3.0% 7/233 • Up to approximately 52 weeks An AE is any untoward medical occurrence, unfavorable, or unintended sign (including an abnormal laboratory finding), symptom, disease, or injury, that ocurred during treatment period. They include events that started after the first dose of study treatment or events that were present prior to start of study treatment but increased in severity during on-treatment period. The safety analysis set included all participants who received at least one dose of study treatment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: (862) 778-8300

Email: novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER