The Purpose of This Study is to Investigate Safety and Tolerability of Tropifexor.

Study Overview
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Brief Summary
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The purpose of this study is to determine whether dosing tropifexor is safe and tolerable.

Detailed Description
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This was a randomized, subject and investigator blinded, multicenter, parallel-arm study to assess the safety and tolerability of tropifexor dosed in the evening as compared to dosing in the morning in subjects with non-alcoholic steatohepatitis (NASH). Subjects whose eligibility was confirmed were randomized with stratification by domicile status at Day 1 of the treatment period into tropifexor (200 μg) AM dose group (hereafter referred to as AM dose group) or tropifexor (200 μg) PM dose group (hereafter referred to as PM dose group) in a 1:1 ratio. Subjects in the AM dose group took tropifexor in the morning and placebo in the evening while subjects in the PM dose group took placebo in the morning and tropifexor in the evening for 4 weeks in a blinded manner.

Official Title
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A Randomized, Investigator and Subject Blinded, Multicenter, Parallel-arm Study to Determine the Safety and Tolerability of Tropifexor.

Conditions
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Liver Disease

Intervention / Treatment
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* Drug: triopifexor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Presence of Liver Disease Exclusion Criteria: Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations. Subjects taking the following medicines UNLESS on a stable dose (within 25% of baseline dose) for at least 3 months before randomization: Type 1 diabetes and Uncontrolled Type 2 diabetes defined as Glycated hemoglobin (HbAlc) ≥ 9.5% at screening -Calculated estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2 (using the Modification of diet in renal disease (MDRD) formula) Subjects with contraindications to Magnetic resonance imaging (MRI) imaging.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tropifexor AM 200 micrograms and Placebo (PM)<br>Tropifexor 200 μg (AM) and Placebo (PM) once daily each | Drug: triopifexor<br>* Tropifexor as a dry blend in hard gelatin capsules for oral administration<br>* Other names: LJN452;Drug: Placebo<br>* Placebo capsules for oral administration<br>|
| Experimental: tropifexor PM 200 micrograms and Placebo (AM)<br>Tropifexor 200 μg (PM) and Placebo (AM) once daily each | Drug: triopifexor<br>* Tropifexor as a dry blend in hard gelatin capsules for oral administration<br>* Other names: LJN452;Drug: Placebo<br>* Placebo capsules for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting circulating LDL-C levels after 2 weeks of tropifexor treatment |  | week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting circulating High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels over 4 weeks of treatment |  | week 4 | 
| Change in ALT, AST and GGT over 4 weeks of treatment |  | week 4 | 
| PK parameters include but not limited to Cmax (ng/ml) will be assessed in the domiciled patients |  | week 4 | 
| PK parameters include but not limited to area under the curve (AUC) will be assessed in the domiciled patients |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tropifexor, FXR agonist