Clinical trial NCT04408937: The Purpose of This Study is to Investigate Safety and Tolerability of Tropifexor.
Official title: A Randomized, Investigator and Subject Blinded, Multicenter, Parallel-arm Study to Determine the Safety and Tolerability of Tropifexor.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liver Disease
Keywords: tropifexor
FXR agonist
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-05-29
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in fasting circulating LDL-C levels after 2 weeks of tropifexor treatment
timeFrame: week 2
Secondary outcomes:
measure: Change in fasting circulating High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels over 4 weeks of treatment
timeFrame: week 4
measure: Change in ALT, AST and GGT over 4 weeks of treatment
timeFrame: week 4
measure: PK parameters include but not limited to Cmax (ng/ml) will be assessed in the domiciled patients
timeFrame: week 4
measure: PK parameters include but not limited to area under the curve (AUC) will be assessed in the domiciled patients
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Madison
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Coronado
country: United States
facility: Novartis Investigative Site
state: California
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: South Bend
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Morehead City
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Hermitage
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
Study officials:
References: