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

NCT05283915 | Completed Phase 1 FDA Drug

• 3 other identifiers: POP16398U1111-1269-68492022-003098-47
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatic Function Abnormal

Outcome Measures

Primary Outcomes (2)

• Assessment of PK parameters Tolebrutinib: AUC

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

  From Day 1 to Day 4

• Assessment of PK parameters M2: AUC

  From Day 1 to Day 4

Secondary Outcomes (5)

• Assessment of PK parameters Tolebrutinib: Cmax

  From Day 1 to Day 4

• Assessment of PK parameters M2: Cmax

  From Day 1 to Day 4

• Assessment of PK parameters Tolebrutinib: AUClast

  From Day 1 to Day 4

• Assessment of PK parameters M2: AUClast

  From Day 1 to Day 4

• Number of participants with treatment-emergent adverse events (TEAEs)

  From Day 1 to Day 8

Study Arms (2)

Mild hepatic impairment group

EXPERIMENTAL

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

Drug: tolebrutinib

Normal hepatic function group

EXPERIMENTAL

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

Drug: tolebrutinib

Interventions

tolebrutinib DRUG

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

Mild hepatic impairment group; Normal hepatic function group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).
• Smoking regularly more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 8 cigarettes per day during the institutionalization.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

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

Related Links

• POP16398 Plain language Results Summary

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 17, 2022
• Study Start: March 18, 2022
• Primary Completion: May 24, 2022
• Study Completion: May 24, 2022
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (2)