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

May 30, 2024 updated by: Principia Biopharma, a Sanofi Company

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
29

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33014
        • Investigational Site Number: 0002
      • Orlando, Florida, United States, 32809
        • Investigational Site Number: 0001

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rilzabrutinib: Mild Hepatic Impairment
Subjects with mild Hepatic Impairment (HI)
Drug: Rilzabrutinib
Rilzabrutinib tablet administered orally
Experimental: Rilzabrutinib: Moderate Hepatic Impairment
Subjects with moderate Hepatic Impairment (HI)
Drug: Rilzabrutinib
Rilzabrutinib tablet administered orally
Experimental: Rilzabrutinib: Healthy-Matched Control
Subjects with normal hepatic function
Drug: Rilzabrutinib
Rilzabrutinib tablet administered orally

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
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
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
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
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
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
Up to 30 hours after rilzabrutinib dosing
Elimination Rate Constant of total rilzabrutinib (Kel)
Time Frame: Up to 30 hours after rilzabrutinib dosing
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
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
Up to 30 hours after rilzabrutinib dosing
Fraction of unbound drug ( rilzabrutinib) expressed as percent (%fu)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Number of Adverse Events (AE) / Serious Adverse Events (SAE)
Time Frame: From date of signed ICF, up to 9 days after rilzabrutinib dosing
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
Time Frame: Up to 30 hours after rilzabrutinib dosing
Up to 30 hours after rilzabrutinib dosing

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area under the concentration-time curve of rilzabrutinib metabolites in plasma from 0 to t (AUC0-t)
Time Frame: Up to 24 hours after rilzabrutinib dosing
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)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Percent of AUC0-inf extrapolated rilzabrutinib metabolites in plasma (%AUCextrap)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Maximum measured concentration of rilzabrutinib metabolites in plasma (Cmax)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Time from dosing to maximum measured concentration of rilzabrutinib metabolites in plasma (tmax)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Terminal Half-Life of rilzabrutinib metabolites in Plasma (t1/2)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Elimination Rate Constant of rilzabrutinib metabolites (Kel)
Time Frame: Up to 24 hours after rilzabrutinib dosing
Up to 24 hours after rilzabrutinib dosing
Metabolite-to-parent ratio (MRAUC)
Time Frame: 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.
Up to 24 hours after rilzabrutinib dosing
Metabolite-to-parent ratio (MRCmax)
Time Frame: 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.
Up to 24 hours after rilzabrutinib dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Principia Biopharma, a Sanofi Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 2, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 23, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 23, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 5, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 5, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • POP17091 (Other Identifier: Sanofi Identifier)
  • U1111-1260-4098 (Registry Identifier: ICTRP)
  • PRN1008-020 (Other Identifier: Sanofi Identifier)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings