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

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

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).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Clinical Research Site Number : 8400001

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis
• Other Study ID Numbers: TDU16831-TDR16862

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