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

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

The purpose of this study is to determine whether dosing tropifexor is safe and tolerable.

Study Overview

• Status: Completed
• Conditions: Liver Disease
• Intervention / Treatment: Drug: triopifexor; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Madison, Alabama, United States, 35758
      • Novartis Investigative Site
  • California
    • Coronado, California, United States, 92118
      • Novartis Investigative Site
  • Florida
    • Miami, Florida, United States, 33014-3616
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32503
      • Novartis Investigative Site
  • Indiana
    • South Bend, Indiana, United States, 46635
      • Novartis Investigative Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Novartis Investigative Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Novartis Investigative Site
    • Knoxville, Tennessee, United States, 37920
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75208-2312
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78215
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novctrd.com
• Results for CLJN452A2113 can be found on the Novartis Clinical Trial Results Website.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2020
• Primary Completion (Actual): November 4, 2020
• Study Completion (Actual): November 4, 2020

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: FXR agonist; tropifexor
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CLJN452A2113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No