Study to Assess the Plasma Concentration of Tolebrutinib Given as a Tablet to Adult Participants With Mild Hepatic Impairment Compared to Participants With Normal Hepatic Function

NCT ID: NCT05283915

Last Updated: 2025-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-18
• Study Completion Date: 2022-05-24

Brief Summary

The purpose of this parallel group, Phase 1, open-label, 2-arm, single dose, multi-center study is to assess the effect of mild hepatic impairment on pharmacokinetics (PK), safety and tolerability of tolebrutinib compared with normal hepatic function, in male and female participants aged 18 to 79 years.

Detailed Description

The total duration of the study per participant is up to 41 days including:

• A screening period of up to 4 weeks (Days -28 to -2)
• A 5-day, open-label treatment period
• Up to 7 days post-treatment follow-up period

Conditions

Hepatic Function Abnormal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mild hepatic impairment group

Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition

Group Type: EXPERIMENTAL

tolebrutinib

Intervention Type: DRUG

Pharmaceutical form: Film-coated tablet Route of administration: oral

Normal hepatic function group

Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition

Group Type: EXPERIMENTAL

tolebrutinib

Intervention Type: DRUG

Pharmaceutical form: Film-coated tablet Route of administration: oral

Interventions

tolebrutinib

Pharmaceutical form: Film-coated tablet Route of administration: oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

For participants with mild hepatic impairment

• Stable chronic liver disease assessed by medical history, physical examination, and laboratory values
• Child-Pugh total score ranging from 5 to 6, inclusive.
• Laboratory parameters within the acceptable range for participants with hepatic impairment; however, estimated glomerular filtration rate (eGFR) should be above or equal to 60 mL/min

For all participants

• 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.
• Participant with platelet count ≥150 000/μL at the screening visit and at Day -1

Exclusion Criteria

For all participants :

• Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from supine to standing position at screening and Day -1
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month).
• History of drug or alcohol abuse within 1 year before inclusion.
• Smoking regularly more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 8 cigarettes per day during the institutionalization.
• Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 72 hours before inclusion.
• Use of any herbal medicines 2 weeks before IMP administration
• Treatment with a strong or moderate CYP3A inhibitors, a strong, moderate or mild CYP2C8 inhibitors OR CYP3A, CYP2C8 inducers within 14 days before the study treatment administration or 5 half-lives, whichever is longer

Specific for participants with mild hepatic impairment:

• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic, renal, infectious disease, moderate or severe hepatic impairment (Child-Pugh total score greater than or equal to 7), or signs of acute illness.
• Hepatocarcinoma.
• Acute liver disease.
• Hepatic encephalopathy Grade 2, 3, and 4.
• Esophageal bleeding which is caused by esophageal varices within 3 months before inclusion.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Clinical Pharmacology of Miami Site Number : 8400002

Miami, Florida, United States

Nucleus Network Site Number : 8400001

Saint Paul, Minnesota, United States

Countries

United States

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25332&tenant=MT_SNY_9011

POP16398 Plain language Results Summary

Other Identifiers

U1111-1269-6849

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-003098-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

POP16398

Identifier Type: -

Identifier Source: org_study_id