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

An Open-label Phase 1, Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Dose in Adult Participants With Mild Hepatic Impairment, and in Matched Participants With Normal Hepatic Function

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Function Abnormal
• Intervention / Treatment: Drug: tolebrutinib

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

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Investigational Site Number 0560001
• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami-Site Number:8400002
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Nucleus Network-Site Number:8400001
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group-NOCCR-Site Number:8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mild hepatic impairment group; Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition	Drug: tolebrutinib; Pharmaceutical form: Film-coated tablet Route of administration: oral
EXPERIMENTAL: Normal hepatic function group; Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition	Drug: tolebrutinib; Pharmaceutical form: Film-coated tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameters Tolebrutinib: Cmax	Maximum plasma concentration observed (Cmax)	From Day 1 to Day 4
Assessment of PK parameters M2: Cmax		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
Assessment of PK parameters Tolebrutinib: AUClast	Area under the serum concentration versus time curve calculated using the trapezoidal method from time zero to the real time Tlast	From Day 1 to Day 4

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 18, 2022
• Primary Completion (ACTUAL): May 24, 2022
• Study Completion (ACTUAL): May 24, 2022

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 16, 2022
• First Posted (ACTUAL): March 17, 2022

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: POP16398; U1111-1269-6849 (REGISTRY: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No