Multiple Sclerosis
Conditions
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).
Interventions
DRUGTolebrutinib
Tablet, oral
DRUGPlacebo
Tablet, oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Part 2: AUC0-tau for SAR442168 metabolite(s) | From Day 1 to Day approximately 14 | Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (24 hours) |
| All Parts: Cmax of SAR442168 | 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 | — |
| 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 | From Day 1 to Day approximately 14 | Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (24 hours) |
Countries
United States
Outcome results
None listed