A Food Effect and Relative Bioavailability Study of Rilzabrutinib in Healthy Participants

A Randomized, Open-label, Single-dose, 4-period, 4--sequence, Crossover Phase I Relative Bioavailability Study Comparing Crystalline Formulation Tablet Versus Reference Amorphous Formulation Tablet of Rilzabrutinib (SAR444671) in Fasted and Fed Conditions in Healthy Male and Female Participants

This is a cross-over, Phase 1, 4-arm study. The purpose of this study is to measure the relative bioavailability and food effect of crystalline formulation rilzabrutinib and amorphous formulation rilzabrutinib in healthy male and female participants aged 18 to 55 years of age.

The total study duration per participant is expected to be up to 36 days, including:

• Screening: up to 4 weeks
• Treatment periods: once successfully screened, enrolled participants will be randomized to 1 of 4 treatment sequences with 4 single dose treatment periods.
• Washout: One day washout is planned after each treatment period hence providing 2 days between doses.
• Safety follow-up: participants will be asked to participate in an end-of-study safety assessment upon discharge from the clinical study unit, ie, on Day 8 of the study.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Autoimmune Disorder
• Intervention / Treatment: Drug: Rilzabrutinib amorphous form; Drug: Rilzabrutinib crystalline form

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Nucleus Network Site Number : 8400001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female, body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive
• Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy participant. Hepatic transaminases (aspartate aminotransferase, alanine aminotransferase) should not exceed 1.25 × the upper laboratory norm (ULN); total bilirubin should not exceed 1 × ULN
• Willing to abstain from using tobacco or nicotine-containing products or consuming alcohol from check-in (Day -1) until discharge at end-of-study visit
• Willing to abstain from taking any prescription drugs, dietary supplements, or non-prescription drugs within 14 days or 5 half-lives, whichever, is longer, prior to the first dose of study drug through the follow-up phone call. Use of hormonal contraception and aspirin (at doses of ≤2000 mg/day) or ibuprofen (at doses of ≤1200 mg/day) are allowed prior to and during the study
• Negative urine drug/alcohol testing at screening and check-in (Day -1). Screening urine drug/alcohol testing may be repeated once if deemed appropriate by the site Investigator
• Willing to abstain from consuming grapefruit, star fruit, or Seville orange-containing products from 14 days prior to first dose of study drug until discharge from the clinical study unit

Exclusion Criteria:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), infectious disease, or signs of acute illness
• Participant has clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, loss of taste and smell, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening. Participant who had severe course of COVID-19 (ie, hospitalization, extracorporeal membrane oxygenation [ECMO], mechanically ventilated)
• Participant has a positive test result for SARS-CoV-2 (measured via Real-time Reverse Transcriptase Polymerase Chain Reaction [RT-PCR] or Rapid Antigen Test [RAT])
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month)
• Blood donation, any volume, within 1 month before inclusion
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure <30 mmHg within 3 minutes when changing from supine to standing position
• 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
• History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis)
• Regular intake of nicotine (via patch, smoking, vaping or other forms) more than 10 mg per day (based on the average nicotine content of 10-12 mg of nicotine per cigarette and inhalation of up to 2 mg of nicotine per cigarette), and unable to stop smoking during the study (occasional smoker can be enrolled)
• Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day)
• If female, pregnancy (defined as positive β-HCG blood test), or breast-feeding
• Any medication (including St John's Wort or ginseng) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of aspirin/ibuprofen, hormonal contraception, and menopausal hormone replacement therapy

• Any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion:

  • Non-live vaccines, including COVID-19: last administration of a vaccine within 4 weeks before randomization
  • Live vaccines: last administration of a vaccine within 3 months before randomization
• Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab)
• Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates)
• Positive alcohol breath or alcohol urine test
• Positive pregnancy test
• Gilbert's Syndrome

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A: SAR444671 amorphous fasted; Participants will receive single oral dose of amorphous tablet formulation rilzabrutinib (SAR444671) under fasted conditions on Day 1 for one period	Drug: Rilzabrutinib amorphous form; Pharmaceutical form:Film coated tablet Route of administration:Oral; Other Names: SAR444671
Experimental: Treatment B: SAR444671 crystalline fasted; Participants will receive single oral dose of crystalline tablet formulation rilzabrutinib (SAR444671) under fasted conditions on Day 1 for one period	Drug: Rilzabrutinib crystalline form; Pharmaceutical form:Film coated tablet Route of administration:Oral; Other Names: SAR444671
Active Comparator: Treatment C: SAR444671 amorphous fed; Participants will receive single oral dose of amorphous tablet formulation rilzabrutinib (SAR444671) under fed conditions on Day 1 for one period	Drug: Rilzabrutinib amorphous form; Pharmaceutical form:Film coated tablet Route of administration:Oral; Other Names: SAR444671
Experimental: Treatment D: SAR444671 crystalline fed; Participants will receive single oral dose of crystalline tablet formulation rilzabrutinib (SAR444671) under fed conditions on Day 1 for one period	Drug: Rilzabrutinib crystalline form; Pharmaceutical form:Film coated tablet Route of administration:Oral; Other Names: SAR444671

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative bioavailability as assessed by rilzabrutinib Cmax following administration of the test and reference formulations in the fasted state	Cmax: maximum plasma concentration	Day 1 to Day 8
Relative bioavailability as assessed by rilzabrutinib AUClast following administration of the test and reference formulations in the fasted state	AUClast: area under the plasma concentration versus time curve from time zero to the last measurable concentration	Day 1 to Day 8
Relative bioavailability as assessed by rilzabrutinib AUC following administration of the test and reference formulations in the fasted state	AUC: area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative bioavailability as assessed by rilzabrutinib Cmax following administration of the test and reference formulations in the fed state	Cmax: maximum plasma concentration	Day 1 to Day 8
Relative bioavailability as assessed by rilzabrutinib AUClast following administration of the test and reference formulations in the fed state	AUClast: area under the plasma concentration versus time curve from time zero to the last measurable concentration	Day 1 to Day 8
Relative bioavailability as assessed by rilzabrutinib AUC following administration of the test and reference formulations in the fed state	AUC: area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 8
Food effects as assessed by rilzabrutinib Cmax following administration of the test and reference formulations under the fed versus fasted state	Cmax: maximum plasma concentration	Day 1 to Day 8
Food effects as assessed by rilzabrutinib AUClast following administration of the test and reference formulations under the fed versus fasted state	AUClast: area under the plasma concentration versus time curve from time zero to the last measurable concentration	Day 1 to Day 8
Food effects as assessed by rilzabrutinib AUC following administration of the test and reference formulations under the fed versus fasted state	AUC: area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 8
Number of participants with adverse events, treatment-emergent adverse events, serious adverse events and adverse events of special interest		Day 1 to Day 8

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• PKM18138 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Actual): April 23, 2024
• Study Completion (Actual): April 23, 2024

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: PKM18138; U1111-1299-1906 (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