A Pharmacokinetic and Tolerability Study of Fexinidazole in a Single Oral Dose in Adult Participants With Mild and Moderate Hepatic Impairment

NCT05607173 | Completed Phase 1 FDA Drug

• 3 other identifiers: POP17145U1111-1266-57942021-004580-27
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 2

Brief Summary

In human, metabolic hepatic clearance represents a significant part of the total clearance of fexinidazole and could be decreased in patients with liver impairment, leading to some overexposure, and conversely, the formation of the 2 active metabolites could be decreased, leading to decreased exposure in hepatic impairment (HI). As there is no experience of use in patients with hepatic impairment, in fexinidazole summary of product characteristics (SmPC) approved by the European Medicines Agency (EMA), fexinidazole is contra-indicated in patients with clinical signs of cirrhosis or jaundice, and in the proposed USA product information, fexinidazole is contra-indicated in patients with liver impairment. Therefore, FDA requested a study with the objective to evaluate the effect of mild and moderate hepatic impairment (HI) on the pharmacokinetics (PK) of fexinidazole and its 2 metabolites, as a post-marketing requirement.

Conditions

Hepatic Function Abnormal

Outcome Measures

Primary Outcomes (2)

• Cmax for fexinidazole and metabolites M1, M2

  Maximum plasma concentration observed (Cmax)

  Day 1 to Day 6

• AUC for fexinidazole and metabolites M1, M2

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

  Day 1 to Day 6

Secondary Outcomes (5)

• tmax for fexinidazole and metabolites M1, M2

  Day 1 to Day 6

• Fexinidazole unbound fraction

  Day 1 and Day 2

• Fexinidazole unbound Cmaxu

  Day 1 and Day 6

• Fexinidazole unbound AUCu

  Day 1 and Day 6

• Number of subjects with Adverse Events (AEs)

  Day 1 to Day 10

Study Arms (3)

Participants with mild HI

EXPERIMENTAL

Mild HI is defined as a total score ranging from 5 to 6, inclusive (Child-Pugh score A)

Drug: Fexinidazole (HOE239)

Participants with moderate HI

EXPERIMENTAL

Moderate HI is defined as a total score ranging from 7 to 9, inclusive (Child-Pugh score B)

Drug: Fexinidazole (HOE239)

Participants with normal hepatic function

EXPERIMENTAL

Participants with normal hepatic function matched to participants

Drug: Fexinidazole (HOE239)

Interventions

Fexinidazole (HOE239) DRUG

Route of administration: oral; pharmaceutical form: tablet

Also known as: Fexinidazole Winthrop®

Participants with mild HI; Participants with moderate HI; Participants with normal hepatic function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants, between 18 and 75 years of age, inclusive
• lead ECG without clinically significant abnormality, in the judgment of the Investigator; normal QT interval confirmed
• Contraception (with double contraception methods) for male and female (unless postmenopausal) participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
• Having given written informed consent prior to any procedure related to the study
• Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research
• Not under any administrative or legal supervision
• Participants with HI
• Body weight between 50.0 and 125.0 kg, inclusive if male, and between 40.0 and 110.0 kg, inclusive if female, body mass index (BMI) between 18.00 and 34.99 kg/m2, inclusive
• Stable chronic liver disease assessed by medical history, physical examination, laboratory values
• Vital signs after 10 minutes resting in supine position within the following range \[or if out of range, considered not clinically significant (NCS) by the Investigator\]:
• mmHg \< systolic blood pressure (SBP) \< 180 mmHg
• mmHg \< diastolic blood pressure (DBP) \< 100 mmHg
• bpm \< HR \< 100 bpm
• Laboratory parameters within the acceptable range for participants with HI; however, serum creatinine should be strictly below the upper laboratory normal
• For moderate HI cohort: Child-Pugh total score ranging from 7 to 9, inclusive

You may not qualify if:

• Participant has clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnea, loss of taste and smell, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening. Participant who had severe course of COVID-19
• Positive test for SARS-CoV-2
• Postural hypotension - symptomatic or asymptomatic (decrease in SBP ≥ 30 mmHg within 3 minutes).
• Excessive consumption of beverages with xanthine bases
• Any participant who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development
• Any participant who cannot be contacted in case of emergency
• Positive alcohol breath test
• Unable or not agreeing to self-complete the hospital anxiety and depression scale (HADS)
• Hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
• Positive result on anti-human immunodeficiency virus 1 and/or 2 antibodies
• Cockayne Syndrome
• Participants with HI
• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecological (if female), or infectious disease, or signs of acute illness
• Hepatocarcinoma
• Acute hepatitis

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Investigational Site Number: 100-0001

Sofia, 1612, Bulgaria

Location

Investigational site 250-0001

Rennes, France

Location

Related Links

• POP17145 Plain Language Results Summary

MeSH Terms

Conditions

Liver Diseases

Interventions

fexinidazole

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 7, 2022
• Study Start: January 18, 2023
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

BU (1); FR (1)