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

Principia Biopharma, a Sanofi Company29 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatic Function Abnormal Healthy Volunteers

Interventions

RilzabrutinibDRUG

Rilzabrutinib tablet administered orally

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (2)

Investigational Site Number: 0002

Miami, Florida, United States

Investigational Site Number: 0001

Orlando, Florida, United States

Outcomes

Primary Outcomes

Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to t (AUC0-t)

Time frame: 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)

Time frame: Up to 30 hours after rilzabrutinib dosing

Percent of AUC0-inf extrapolated total rilzabrutinib in plasma (%AUCextrap )

Time frame: Up to 30 hours after rilzabrutinib dosing

Maximum measured concentration of total rilzabrutinib in plasma (Cmax)

Time frame: Up to 30 hours after rilzabrutinib dosing

Time from dosing to maximum measured concentration of total rilzabrutinib in plasma (tmax)

Time frame: Up to 30 hours after rilzabrutinib dosing

Terminal Half-Life of total rilzabrutinib in Plasma (t1/2)

Time frame: Up to 30 hours after rilzabrutinib dosing

Elimination Rate Constant of total rilzabrutinib (Kel)

Time frame: Up to 30 hours after rilzabrutinib dosing

Apparent Total Clearance of rilzabrutinib in the plasma after extra-vascular administration (CL/F)

Time frame: Up to 30 hours after rilzabrutinib dosing

Apparent Volume of Distribution during the Terminal elimination phase after extravascular administration (Vz/F)

Time frame: Up to 30 hours after rilzabrutinib dosing

Fraction of unbound drug ( rilzabrutinib) expressed as percent (%fu)

Data from ClinicalTrials.gov

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