Clinical trial NCT06444204: A Study to Evaluate the Effect of Mild and Moderate Hepatic Impairment on the Single-Dose Pharmacokinetics of Rilzabrutinib (PRN1008)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Function Abnormal
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-06-05
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the concentration-time curve of total rilzabrutinib in plasma from 0 to t (AUC0-t)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Area under the concentration-time curve of total rilzabrutinib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Percent of AUC0-inf extrapolated total rilzabrutinib in plasma (%AUCextrap )
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Maximum measured concentration of total rilzabrutinib in plasma (Cmax)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Time from dosing to maximum measured concentration of total rilzabrutinib in plasma (tmax)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Terminal Half-Life of total rilzabrutinib in Plasma (t1/2)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Elimination Rate Constant of total rilzabrutinib (Kel)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Apparent Total Clearance of rilzabrutinib in the plasma after extra-vascular administration (CL/F)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Apparent Volume of Distribution during the Terminal elimination phase after extravascular administration (Vz/F)
timeFrame: Up to 30 hours after rilzabrutinib dosing
measure: Fraction of unbound drug ( rilzabrutinib) expressed as percent (%fu)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Number of Adverse Events (AE) / Serious Adverse Events (SAE)
timeFrame: From date of signed ICF, up to 9 days after rilzabrutinib dosing
measure: Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities
timeFrame: Up to 30 hours after rilzabrutinib dosing
Secondary outcomes:
measure: Area under the concentration-time curve of rilzabrutinib metabolites in plasma from 0 to t (AUC0-t)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Area under the concentration-time curve of rilzabrutinib metabolites in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Percent of AUC0-inf extrapolated rilzabrutinib metabolites in plasma (%AUCextrap)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Maximum measured concentration of rilzabrutinib metabolites in plasma (Cmax)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Time from dosing to maximum measured concentration of rilzabrutinib metabolites in plasma (tmax)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Terminal Half-Life of rilzabrutinib metabolites in Plasma (t1/2)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Elimination Rate Constant of rilzabrutinib metabolites (Kel)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Metabolite-to-parent ratio (MRAUC)
timeFrame: Up to 24 hours after rilzabrutinib dosing
measure: Metabolite-to-parent ratio (MRCmax)
timeFrame: Up to 24 hours after rilzabrutinib dosing
Other outcomes:
Locations:
city: Miami
country: United States
facility: Investigational Site Number: 0002
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number: 0001
state: Florida
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: