Study of Drug-drug Interaction of the Effects of Gemfibrozil and Rifampicin on SAR442168 in Healthy Adult Subjects

A Phase 1, Single-center, Open-label, Two-cohort, Two-period, One-sequence, Two Treatment, Drug-drug Interaction Study of the Effects of Gemfibrozil and Rifampicin on SAR442168 in Healthy Subjects

This is a Phase 1, single-center, open-label, non-randomized study to assess the effects of CYP2C8 inhibition using gemfibrozil, and CYP3A4 and CYP2C8 induction using rifampicin on the pharmacokinetics of SAR442168 in healthy male participants aged 18 to 45 years.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Tolebrutinib; Drug: gemfibrozil; Drug: rifampicin

Detailed Description

Study duration per participant approximately 16 days for Cohort 1 and approximately 18 days for Cohort 2.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55144
      • Prism Research-Site Number:8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male participant, between 18 and 45 years of age, inclusive.
• Body weight between 50.0 and 100.0 kg, inclusive, body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive.
• Having given written informed consent prior to undertaking any study-related procedure.

Exclusion Criteria:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Participants with known hypersensitivity to any component of the IMP formulation or allergic disease diagnosed and treated by a physician.
• Any medication (including St John's Wort and ginseng) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion.
• Any contraindications to gemfibrozil or rifampicin, according to the applicable labelling.
• Any subject 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.

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: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; SAR442168 administered alone and together with gemfibrozil. 1 day washout for each administration of SAR442168.	Drug: Tolebrutinib; Tablet, taken orally; Drug: gemfibrozil; Tablet, taken orally
Experimental: Cohort 2; SAR442168 administered alone and together with rifampicin. 1 day washout for each administration of SAR442168.	Drug: Tolebrutinib; Tablet, taken orally; Drug: rifampicin; Tablet, taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: AUClast of SAR442168	AUC up to the last measurable concentration	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2
Pharmacokinetics: AUC of SAR442168	Area under the curve, reflects the concentration of drug	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Maximum plasma concentration observed (Cmax) of SAR442168	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2
Pharmacokinetics: Cmax of SAR442168 metabolite(s)	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2
Pharmacokinetics: AUC of SAR442168 metabolite(s)	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2
Pharmacokinetics: Time to reach Cmax (tmax) of SAR442168	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2
Pharmacokinetics: tmax of SAR442168 metabolite(s)	Cohort 1: day1 period 1 to day 7 period 2; Cohort 2: day1 period 1 to day 9 period 2
Pharmacokinetics: Cmax of gemfibrozil	From Day 1 to Day 7 of Period 2
Pharmacokinetics: Cmax of gemfibrozil 1-O-glucuronide	From Day 1 to Day 7 of Period 2
Pharmacokinetics: tmax of gemfibrozil	From Day 1 to Day 7 of Period 2
Pharmacokinetics: tmax of gemfibrozil 1-O-glucuronide	From Day 1 to Day 7 of Period 2
Pharmacokinetics: Cmax of rifampicin	From Day 1 to Day 9 of Period 2
Pharmacokinetics: tmax of rifampicin	From Day 1 to Day 9 of Period 2
Numbers of participants with adverse events (AEs)	From baseline to End of Study (i.e. Period 2 Day 16 days in Cohort 1, and Period 2 Day18 days in Cohort 2)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• INT16726 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Actual): July 8, 2020
• Study Completion (Actual): July 8, 2020

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Ethers; Fatty Acids; Lipids; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Polycyclic Compounds; Phenols; Benzene Derivatives; Pentanoic Acids; Valerates; Fatty Acids, Volatile; Heterocyclic Compounds, 4 or More Rings; Butyrates; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Phenyl Ethers; Fibric Acids; Isobutyrates; Rifampin; Gemfibrozil
• Other Study ID Numbers: INT16726; U1111-1244-2759 (Registry Identifier: 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