A Study in Adults to Investigate the Impact of Mild, Moderate, and Severe Hepatic Impairment on Pharmacokinetics of Venglustat Compared to Participants With Normal Hepatic Function

NCT05718258 | Completed Phase 1 FDA Drug

• 3 other identifiers: POP16551U1111-1261-75002022-000945-34
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a parallel, Phase 1, four arm, open-label, single dose, multicenter study to evaluate the impact of hepatic impairment on venglustat exposure following treatment with venglustat. The purpose of this study is to assess the effect of mild, moderate, and severe hepatic impairment on PK, safety, and tolerability of venglustat compared with normal hepatic function in male and female participants aged 18 to 79 years. Study details include:

• The total study duration per participant will be up to 42 days, including up to 21 days for screening and approximately 21 days from institutionalization to the end of study (EOS).
• Institutionalization is mandatory until the activities on D5 have been completed.
• Each participant will receive a single dose of venglustat.
• For hepatically impaired participants there will be a screening visit, a multi-day institutionalization visit, and 7 site visits after D5 discharge, including the end of study (EOS) visit.
• For healthy volunteers there will be a screening visit, a multi-day institutionalization visit and 3 site visits after D5 discharge, including the end of study (EOS) visit.

Conditions

Hepatic Function Abnormal

Outcome Measures

Primary Outcomes (2)

• Maximum venglustat plasma concentration observed (Cmax)

  Baseline to Day 20

• Area under the plasma concentration versus time curve extrapolated to infinity (AUC)

  Baseline to Day 20

Secondary Outcomes (2)

• Time to maximum venglustat plasma concentration (tmax)

  Baseline to Day 20

• Number of participants with adverse event (AE), treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESI)

  Baseline to Day 20

Study Arms (4)

Participants with mild hepatic impairment

EXPERIMENTAL

Venglustat single dose on Day 1

Drug: Venglustat (GZ402671)

Participants with normal hepatic function

EXPERIMENTAL

Venglustat single dose on Day 1

Drug: Venglustat (GZ402671)

Participants with moderate hepatic impairment

EXPERIMENTAL

Venglustat single dose on Day 1

Drug: Venglustat (GZ402671)

Participants with severe hepatic impairment

EXPERIMENTAL

Venglustat single dose on Day 1

Drug: Venglustat (GZ402671)

Interventions

Venglustat (GZ402671) DRUG

Pharmaceutical form: tablet Route of administration: oral

Participants with mild hepatic impairment; Participants with moderate hepatic impairment; Participants with normal hepatic function; Participants with severe hepatic impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 79 years of age inclusive, at the time of signing the informed consent.
• Body weight between 50.0 and 115.0 kg, inclusive, if male; between 40.0 and 100 kg, inclusive, if female, and body mass index (BMI) within the range 18 to 40 kg/m2, inclusive, at screening.
• Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
• Female participants must refrain from donating ova/ovum.
• Capable of giving signed informed consent.
• Participants with mild, moderate, and severe hepatic impairment
• Stable chronic liver disease assessed by medical history, physical examination, and laboratory values. Hepatic impairment will be assessed according to the Child-Pugh classification, using CPS (Mild hepatic impairment is defined as a total score ranging from 5 to 6, inclusive (CPS-A); Moderate hepatic impairment is defined as a total score ranging from 7 to 9, inclusive (CPS-B); and severe hepatic impairment is defined as a total score ranging from 10 to 15, inclusive (CPS-C).
• Laboratory parameters within the acceptable range for participants with hepatic impairment; however, serum creatinine should be strictly at or below the upper laboratory norm and eGFR should be \>= 60 mL/min.
• Participants with normal hepatic function
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
• Laboratory parameters within the reference range for healthy participants.

You may not qualify if:

• Participant who had severe course of COVID-19 (i.e., hospitalization, extracorporeal membrane oxygenation, mechanically ventilated) within the past 8 weeks.
• History of current recreational drugs or alcohol abuse.
• Smoking more than 15 cigarettes or equivalent per day.
• Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in SBP ≥30 mmHg within 3 minutes when changing from supine to standing position at screening and Day 1.
• Positive result on drug or alcohol screen.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
• Any participant who cannot comply with the following study restrictions: refraining from drinking alcohol, tea, coffee, chocolate, quinine, or caffeine-containing beverages from 1 day before institutionalization and throughout the study duration; following a stable lifestyle with no intensive physical activity from 1 day prior to institutionalization throughout the study duration until after collection of the final PK sample.
• Positive result on anti-human immunodeficiency virus (HIV) or COVID-19 test.
• Participants with mild, moderate, and severe hepatic impairment
• Hepatocellular carcinoma.
• Acute hepatitis.
• Uncontrolled or decompensated hepatic encephalopathy. Encephalopathy grade \> 2.
• Any participant enrolled in or having participated in this or any other clinical study involving an IMP or in any other type of medical research according to applicable regulations within the past 14 days or 5 half-lives before screening, whichever is longer, per local regulations.
• Participants with normal hepatic functions
• Any history or presence of clinically relevant hepatic or renal disease.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (6)

Inland Empire Liver Foundation Site Number : 8400004

Rialto, California, 92377, United States

Location

Clinical Pharmacology of Miami Site Number : 8400002

Miami, Florida, 33014, United States

Location

Nucleus Network Site Number : 8400001

Saint Paul, Minnesota, 55114, United States

Location

Volunteer Research Group-NOCCR Site Number : 8400003

Knoxville, Tennessee, 37920, United States

Location

American Research Corporation Site Number : 8400005

San Antonio, Texas, 78215, United States

Location

Investigational Site Number : 2760001

Kiel, 24105, Germany

Location

Related Links

• POP16551 Plain Language Results Summary

MeSH Terms

Conditions

Liver Diseases

Interventions

venglustat

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 8, 2023
• Study Start: January 18, 2023
• Primary Completion: January 29, 2024
• Study Completion: January 29, 2024
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); US (5)