A Study to Evaluate the Effect of Mild and Moderate Hepatic Impairment on the Single-Dose Pharmacokinetics of Rilzabrutinib (PRN1008)

An Open-Label, Phase 1 Study to Evaluate the Effect of Mild and Moderate Hepatic Impairment on the Single-Dose Pharmacokinetics of Rilzabrutinib (PRN1008)

This is a single-dose study to assess the effect of mild or moderate Hepatic Impairment (HI) on the Pharmacokinetics (PK) of rilzabrutinib as well as to evaluate the safety and tolerability of rilzabrutinib in subjects with HI.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hepatic Function Abnormal
• Intervention / Treatment: Drug: Rilzabrutinib

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Investigational Site Number: 0002
    • Orlando, Florida, United States, 32809
      • Investigational Site Number: 0001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Hepatic Impaired Subjects:

  • Non-smoking or light smoker (not exceeding 5 cigarettes per day), adult male or non-pregnant, non-lactating female, 18-75 years of age, inclusive, at screening.
  • Weight ≥ 50 kg, at screening.

• Healthy Subjects:

  • Non-smoking or light smoker (not exceeding 5 cigarettes per day), healthy, adult males and non-pregnant, non-lactating females, 18-75 years of age, inclusive, at screening.

Subject must be matched for age (within ± 10 years), and sex of the matched subject with hepatic impairment.

--Weight ≥ 50 kg at screening.

Additional inclusion criteria might apply.

Exclusion Criteria:

• Hepatic Impaired Subjects:

  • Pregnant or lactating female.
  • Uncontrolled treated/untreated hypertension (systolic blood pressure ≥ 160 millimeters of mercury [mmHg] and/or diastolic blood pressure ≥ 105 mmHg), or resting pulse rate < 45 or > 100 beats per minute (bpm). Measurements may be repeated once in order to determine eligibility.

• Healthy Subjects

  • Pregnant or lactating female.
  • Uncontrolled treated/untreated hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 105 mmHg), or resting pulse rate < 45 or > 100 bpm. Measurements may be repeated once in order to determine eligibility.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rilzabrutinib: Mild Hepatic Impairment; Subjects with mild Hepatic Impairment (HI)	Drug: Rilzabrutinib; Rilzabrutinib tablet administered orally
Experimental: Rilzabrutinib: Moderate Hepatic Impairment; Subjects with moderate Hepatic Impairment (HI)	Drug: Rilzabrutinib; Rilzabrutinib tablet administered orally
Experimental: Rilzabrutinib: Healthy-Matched Control; Subjects with normal hepatic function	Drug: Rilzabrutinib; Rilzabrutinib tablet administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to t (AUC0-t)	Up to 30 hours after rilzabrutinib dosing
Area under the concentration-time curve of total rilzabrutinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)	Up to 30 hours after rilzabrutinib dosing
Percent of AUC0-inf extrapolated total rilzabrutinib in plasma (%AUCextrap )	Up to 30 hours after rilzabrutinib dosing
Maximum measured concentration of total rilzabrutinib in plasma (Cmax)	Up to 30 hours after rilzabrutinib dosing
Time from dosing to maximum measured concentration of total rilzabrutinib in plasma (tmax)	Up to 30 hours after rilzabrutinib dosing
Terminal Half-Life of total rilzabrutinib in Plasma (t1/2)	Up to 30 hours after rilzabrutinib dosing
Elimination Rate Constant of total rilzabrutinib (Kel)	Up to 30 hours after rilzabrutinib dosing
Apparent Total Clearance of rilzabrutinib in the plasma after extra-vascular administration (CL/F)	Up to 30 hours after rilzabrutinib dosing
Apparent Volume of Distribution during the Terminal elimination phase after extravascular administration (Vz/F)	Up to 30 hours after rilzabrutinib dosing
Fraction of unbound drug ( rilzabrutinib) expressed as percent (%fu)	Up to 24 hours after rilzabrutinib dosing
Number of Adverse Events (AE) / Serious Adverse Events (SAE)	From date of signed ICF, up to 9 days after rilzabrutinib dosing
Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities	Up to 30 hours after rilzabrutinib dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve of rilzabrutinib metabolites in plasma from 0 to t (AUC0-t)		Up to 24 hours after rilzabrutinib dosing
Area under the concentration-time curve of rilzabrutinib metabolites in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)		Up to 24 hours after rilzabrutinib dosing
Percent of AUC0-inf extrapolated rilzabrutinib metabolites in plasma (%AUCextrap)		Up to 24 hours after rilzabrutinib dosing
Maximum measured concentration of rilzabrutinib metabolites in plasma (Cmax)		Up to 24 hours after rilzabrutinib dosing
Time from dosing to maximum measured concentration of rilzabrutinib metabolites in plasma (tmax)		Up to 24 hours after rilzabrutinib dosing
Terminal Half-Life of rilzabrutinib metabolites in Plasma (t1/2)		Up to 24 hours after rilzabrutinib dosing
Elimination Rate Constant of rilzabrutinib metabolites (Kel)		Up to 24 hours after rilzabrutinib dosing
Metabolite-to-parent ratio (MRAUC)	MRAUC is Based on AUC0-t, corrected for Molecular weights (MW). MRAUC = (AUC0-t,M/AUC0-t,P) x (MW,P/MW,M) where M was metabolite and P was parent.	Up to 24 hours after rilzabrutinib dosing
Metabolite-to-parent ratio (MRCmax)	MRCmax is based on Cmax, corrected for MW. MRCmax = (Cmax,M/ Cmax,P) x (MW,P/MW,M) where M was metabolite and P was parent.	Up to 24 hours after rilzabrutinib dosing

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): November 2, 2020
• Primary Completion (Actual): March 23, 2021
• Study Completion (Actual): March 23, 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: POP17091 (Other Identifier: Sanofi Identifier); U1111-1260-4098 (Registry Identifier: ICTRP); PRN1008-020 (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