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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06444204
• Other study ID #: POP17091
• Secondary ID: U1111-1260-4098P
• Status: Completed
• Phase: Phase 1
• Start date: November 2, 2020
• Est. completion date: March 23, 2021

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: March 23, 2021
• Est. primary completion date: March 23, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Rilzabrutinib
Rilzabrutinib tablet administered orally

Locations

Country	Name	City	State
United States	Investigational Site Number: 0002	Miami	Florida
United States	Investigational Site Number: 0001	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Principia Biopharma, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

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