Study of the Tolerability and Pharmacokinetics of Oral Doses of SAR442168 With a Food Effect Investigation in Healthy Adult Participants

Study Overview
=================
Brief Summary
-----------------
This is a randomized, placebo-controlled, four-part, Phase I, first in human (FIH) study to assess the tolerability and pharmacokinetics (PK) of ascending single and 14-day repeated oral doses of SAR442168 with a food effect investigation in healthy adult participants. In Part 1a: The tolerability and safety of SAR442168 and the pharmacokinetic parameters of SAR442168 and metabolite(s)after ascending single oral doses in fasted and fed conditions In Part 1b: The relationship of PK of SAR442168 and metabolite(s) in cerebrospinal fluid (CSF) to that in plasma after single oral doses given in fed conditions (moderate-fat meal) In Part 1c: The effect of a high-fat meal on the pharmacokinetics of SAR442168 and metabolite(s) (high-fat) In Part 1d: The effect of a high-fat meal on the pharmacokinetics of SAR442168 and metabolite(s) (standardized high-fat meal) In Part 2: The tolerability and safety of SAR442168 and the pharmacokinetic parameters of SAR442168 and metabolite(s) after 14-day ascending repeated oral doses of SAR442168 given in fed conditions (moderate-fat meal).

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Study of the Tolerability and Pharmacokinetics of Ascending Single and 14-day Repeated Oral Doses of SAR442168 With a Food Effect Investigation in Healthy Adult Participants

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: Tolebrutinib
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Having given written informed consent prior to undertaking any study-related procedure. Exclusion Criteria: 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
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1a<br>3 single ascending doses of SAR442168 or placebo in fasted and fed (high-fat breakfast) conditions | Drug: Tolebrutinib<br>* Tablet, oral<br>* Other names: SAR442168;Drug: Placebo<br>* Tablet, oral<br>|
| Experimental: Part 1b<br>2 single doses of SAR442168 under fed conditions (moderate-fat breakfast). | Drug: Tolebrutinib<br>* Tablet, oral<br>* Other names: SAR442168;|
| Experimental: Part 1c<br>1 single dose of SAR442168 under fasting and fed conditions (high-fat breakfast). | Drug: Tolebrutinib<br>* Tablet, oral<br>* Other names: SAR442168;|
| Experimental: Part 1d<br>1 single dose of SAR442168 under fasting and fed conditions (Standardized high-fat breakfast). | Drug: Tolebrutinib<br>* Tablet, oral<br>* Other names: SAR442168;|
| Experimental: Part 2<br>3 ascending once-daily repeated single doses of SAR442168 or placebo for 14 days under fed conditions (moderate-fat breakfast) | Drug: Tolebrutinib<br>* Tablet, oral<br>* Other names: SAR442168;Drug: Placebo<br>* Tablet, oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1a and Part 2: Number of participants with Adverse Events (AEs) and treatment-emergent adverse events (TEAEs) |  | Part 1a: Day 1 to approximately Day 14 Part 2: Day 1 to approximately Day 21 | 
| Part 1b: Total (free and bound) SAR442168 concentrations in CSF |  | From Day 1 to Day 3 | 
| Part 1b: Total (free and bound) SAR442168 metabolite(s) concentrations in CSF |  | From Day 1 to Day 3 | 
| Part 1c and Part 1d: Maximum plasma concentration observed (Cmax) ratio fed/fast of SAR442168 |  | From Day 1 to Day approximately 14 | 
| Part 1c and Part1d: Cmax ratio fed/fasted of SAR442168 metabolite(s) |  | From Day 1 to Day approximately 14 | 
| Part 1c and Part 1d: Area under the plasma concentration versus time curve (AUC) ratio fed/fast of SAR442168 |  | From Day 1 to Day approximately 14 | 
| Part 1c and Part1d: AUC ratio fed/fast of SAR442168 metabolite(s) |  | From Day 1 to Day approximately 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Parts: Cmax of SAR442168 |  | From Day 1 to Day approximately 14 | 
| All Parts: Cmax of SAR442168 metabolite(s) |  | From Day 1 to Day approximately 14 | 
| Part 1a, Part 1b and Part 2: tmax of SAR442168 |  | From Day 1 to Day approximately 14 | 
| Part 1a, Part 1b and Part 2: tmax of SAR442168 metabolite(s) |  | From Day 1 to Day approximately 14 | 
| Part 1a, Part 1b, Part1c and Part 1d: AUC of SAR442168 |  | From Day 1 to Day approximately 14 | 
| Part 1a, Part 1b, Part1c and Part 1d: AUC of SAR442168 metabolite(s) |  | From Day 1 to Day approximately 14 | 
| Part 2: AUC0-tau for SAR442168 | Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (24 hours) | From Day 1 to Day approximately 14 | 
| Part 2: AUC0-tau for SAR442168 metabolite(s) | Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (24 hours) | From Day 1 to Day approximately 14 | 
| Part 1b, Part1c and 1d: Number of participants with Adverse Events (AEs) and treatment-emergent adverse events (TEAEs) |  | From Day 1 to Day approximately 14 |