Pharmacokinetics (PK) of Rilzabrutinib (PRN1008) in Healthy Japanese and Caucasian Subjects

A Phase 1, Single-Center, Open-Label Study to Evaluate the Pharmacokinetics and Tolerability of Rilzabrutinib (PRN1008) in Japanese and Caucasian Healthy Male and Female Subjects

This is a single-dose and multiple doses study to assess the Pharmacokinetics (PK) of rilzabrutinib as well as to evaluate the tolerability of rilzabrutinib in Japanese and Caucasian Healthy Male and Female subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Rilzabrutinib

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Investigational Site Number: 0001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Japanese subjects must have both biological parents and all four grandparents of Japanese ancestry and born in a Japanese country of origin.
• Caucasian subjects must have four Caucasian grandparents (Hispanics of white race can be considered Caucasian).
• Healthy adult male or non-pregnant non-lactating females, 18 to 75 years of age (inclusive) at the time of screening.
• Body mass index (BMI) ≥18 and ≤35 (kg/m2), inclusive, and a minimum body weight of 45 kg.

Additional inclusion criteria might apply.

Exclusion Criteria:

• Symptoms consistent with COVID-19 such as fever, cough, and shortness of breath within 14 days before Day 1.
• Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening or check-in (Day -1).
• Known previous COVID-19 infection.
• Use of any prescription or over-the-counter (OTC) medication, herbal products, or dietary supplements within the 7 days or 5 half-lives, whichever is longer, prior to the first study drug administration. Use of hormonal contraception is allowed prior to and during the study.

Additional exclusion criteria might apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Rilzabrutinib	Drug: Rilzabrutinib; Rilzabrutinib tablet(s) administered orally
Experimental: Cohort 2: Rilzabrutinib	Drug: Rilzabrutinib; Rilzabrutinib tablet(s) administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum measured concentration of total rilzabrutinib in plasma (Cmax)	Up to 48 hours after the last rilzabrutinib dose
Time from dosing to maximum measured concentration of total rilzabrutinib in plasma (tmax)	Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to the last measurable concentration (AUC0-last)	Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of total rilzabrutinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)	Up to 48 hours after the last rilzabrutinib dose
Area under the plasma concentration-time curve of total rilzabrutinib from zero during the dosage interval (AUC0-tau)	Up to 48 hours after the last rilzabrutinib dose
Terminal Half-Life of total rilzabrutinib in Plasma (t1/2)	Up to 48 hours after the last rilzabrutinib dose
Apparent Total Clearance of rilzabrutinib in the plasma after oral administration (CL/F)	Up to 48 hours after the last rilzabrutinib dose
Apparent volume of distribution after oral administration (Vd/F)	Up to 48 hours after the last rilzabrutinib dose
Dose proportionality of rilzabrutinib	Up to 48 hours after the last rilzabrutinib dose
Accumulation ratio (Rac)	Up to 48 hours after the last rilzabrutinib dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities	Up to 14 days after rilzabrutinib dosing
Number of Adverse Events (AE) / Serious Adverse Events (SAE)	From date of signed ICF, up to 47 days
Bruton's Tyrosine Kinase (BTK) Occupancy characterization	Up to 48 hours after the last rilzabrutinib dose
Maximum measured concentration of rilzabrutinib metabolites in plasma (Cmax)	Up to 48 hours after the last rilzabrutinib dose
Time from dosing to maximum measured concentration of rilzabrutinib metabolites in plasma (tmax)	Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of rilzabrutinib metabolites in plasma from 0 to the last measurable concentration (AUC0-last)	Up to 48 hours after the last rilzabrutinib dose
Area under the concentration-time curve of rilzabrutinib metabolites in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)	Up to 48 hours after the last rilzabrutinib dose
Area under the plasma concentration-time curve of rilzabrutinib metabolites from zero during the dosage interval (AUC0-tau)	Up to 48 hours after the last rilzabrutinib dose
Terminal Half-Life of rilzabrutinib metabolites in Plasma (t1/2)	Up to 48 hours after the last rilzabrutinib dose

Collaborators and Investigators

• Sponsor: Principia Biopharma, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): April 12, 2021
• Study Completion (Actual): April 12, 2021

Study Registration Dates

• First Submitted: May 30, 2024
• First Submitted That Met QC Criteria: May 30, 2024
• First Posted (Actual): June 5, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PKM17089 (Other Identifier: Sanofi Identifier); U1111-1260-4452 (Registry Identifier: ICTRP); PRN1008-023 (Other Identifier: Sanofi Identifier)

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