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

Study Overview
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Brief Summary
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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.

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

Official Title
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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

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Tolebrutinib
* Drug: gemfibrozil
* Drug: rifampicin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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) |