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

NCT06444204 | Completed Phase 1 FDA Drug

• 3 other identifiers: POP17091U1111-1260-4098PRN1008-020
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hepatic Function Abnormal; Healthy Volunteers

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (9)

• 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

Study Arms (3)

Rilzabrutinib: Mild Hepatic Impairment

EXPERIMENTAL

Subjects with mild Hepatic Impairment (HI)

Drug: Rilzabrutinib

Rilzabrutinib: Moderate Hepatic Impairment

EXPERIMENTAL

Subjects with moderate Hepatic Impairment (HI)

Drug: Rilzabrutinib

Rilzabrutinib: Healthy-Matched Control

EXPERIMENTAL

Subjects with normal hepatic function

Drug: Rilzabrutinib

Interventions

Rilzabrutinib DRUG

Rilzabrutinib tablet administered orally

Rilzabrutinib: Healthy-Matched Control; Rilzabrutinib: Mild Hepatic Impairment; Rilzabrutinib: Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Principia Biopharma, a Sanofi Company: lead

Study Sites (2)

Investigational Site Number: 0002

Miami, Florida, 33014, United States

Location

Investigational Site Number: 0001

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: June 5, 2024
• Study Start: November 2, 2020
• Primary Completion: March 23, 2021
• Study Completion: March 23, 2021
• Last Updated: June 5, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2)