Healthy Volunteers, Hepatic Function Abnormal
Conditions
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.
Interventions
DRUGRilzabrutinib
Rilzabrutinib tablet administered orally
Sponsors
Principia Biopharma, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities | 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 24 hours after rilzabrutinib dosing | 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. |
| Metabolite-to-parent ratio (MRCmax) | Up to 24 hours after rilzabrutinib dosing | 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. |
| Area under the concentration-time curve of rilzabrutinib metabolites in plasma from 0 to t (AUC0-t) | Up to 24 hours after rilzabrutinib dosing | — |
Countries
United States
Outcome results
None listed