A Study of Vorasidenib in Participants With Moderate or Mild Hepatic Impairment and Matched Participants With Normal Hepatic Function

NCT05674474 | Completed Phase 1 FDA Drug

• 1 other identifier: PKH-95032-008
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to estimate the effect of moderate or mild hepatic impairment on the pharmacokinetic (PK) profile of a single oral dose of 20 mg vorasidenib in participants with hepatic impairment relative to healthy matched control participants with normal hepatic function.

Conditions

Hepatic Impairment

Keywords

Vorasidenib

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) of Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-t) for Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• AUC From Time 0 Extrapolated to Infinity (AUC0-inf) for Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

Secondary Outcomes (15)

• Apparent Terminal Elimination Half-life (t1/2) of Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• Apparent Oral Clearance (CL/F) for Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• Apparent Volume of Distribution (Vz/F) of Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• Area Under the Unbound Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t,u) for Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

• Area Under the Unbound Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf,u) for Vorasidenib

  Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose

Study Arms (2)

Group A: Normal Hepatic Function

EXPERIMENTAL

Participants with normal hepatic function will receive a single oral dose of 20 mg (2 × 10 mg) vorasidenib tablets on Day 1.

Drug: Vorasidenib

Group B: Moderate or Mild Hepatic Impairment

EXPERIMENTAL

Stage 1: Participants with moderate hepatic impairment (Child-Pugh \[C-P\] Class B, score of 7 to 9) will receive a single oral dose of 20 mg (2 × 10 mg) vorasidenib tablets on Day 1. Stage 2: Participants with mild hepatic impairment (C-P Class A, score of 5 to 6) will receive a single oral dose of 20 mg (2 × 10 mg) vorasidenib tablets on Day 1. Stage 2 will be conducted if a clinically meaningful increase in exposure of vorasidenib is observed in participants with moderate hepatic impairment in Stage 1.

Drug: Vorasidenib

Interventions

Vorasidenib DRUG

Administered orally as tablets.

Also known as: S095032, AG-881

Group A: Normal Hepatic Function; Group B: Moderate or Mild Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a body mass index of 18 to 40 kilograms per square meter (kg/m\^2).
• Female participants of childbearing potential must use 2 effective methods of birth control during the study and for 90 days after the last dose of vorasidenib or be surgically sterile, or postmenopausal.
• Male participants with female partners of childbearing potential must be sterile, or willing to use 2 effective methods of birth control from Screening until at least 90 days after the last dose of the study drug, or practice abstinence during the study.
• Non-smoker or uses ≤10 cigarettes per day as judged by the investigator.
• Agree to comply with all protocol requirements for the duration of the study.
• Able to provide written informed consent prior to any procedure required by the study.
• Have normal hepatic function.
• Have chronic (more than 6 months) and stable hepatic impairment (i.e., no acute episodes of illness within 30 days before Screening due to deterioration of hepatic function) as assessed by a Child-Pugh classification score of moderate (7 to 9 points) and, if Stage 2 enrolls, mild (5 to 6 points).
• The subject has grade 0 or grade 1 hepatic encephalopathy, considered stable per investigator assessment, without exacerbation within the 6 months prior to Screening.
• The subject has a QTcF of ≤480 msec.

You may not qualify if:

• Have a history or clinical manifestations of a significant neurological, renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, or psychiatric disease that would preclude study participation, as judged by the investigator.
• Have a history (within 5 years) or presence of malignancy, except for adequately treated basal cell and squamous cell carcinoma of the skin.
• The subject is a woman of childbearing potential who is pregnant, lactating, or planning to become pregnant within 90 days after the last dose of study drug or the subject is on oral contraceptive pills within 14 days or 5 half-lives (whichever is longer) prior to the first dose administration and during the study.
• Have received any vaccine or used any prescription (excluding hormone replacement therapy) or over-the-counter medications, including herbal or nutritional supplements, within 30 days before the first dose of the study drug.
• Have a positive test result for hepatitis B surface antigen or antibodies to hepatitis C virus.
• Have a positive test result for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Have a positive test result for human immunodeficiency virus (HIV) types 1 or 2 antibodies.
• Have used strong or moderate CYP1A2 inhibitors and/or inducers within 14 days or 5 half-lives, whichever is longer, prior to the first dose administration. .
• Have used any gastric acid reducing agents (eg, proton-pump inhibitors, H2-receptor antagonists, antacids) or drugs that can prolong the QT interval for 28 days or 5 drug half-lives (whichever is longer) prior to the first dosing and throughout the study
• Have a history of severe and/or uncontrolled ventricular arrhythmias or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome).
• Have a history of alcoholism or drug abuse within 3 months before Screening or excessive alcohol consumption.
• Unable or unwilling to abstain from recreational drugs, alcohol, caffeine, xanthine-containing beverages or food (e.g., coffee, tea, chocolate, and caffeinated sodas, colas), grapefruit, grapefruit juice, Seville oranges, or products containing any of these, from 48 hours prior to study drug dosing until discharge.
• Involved in strenuous activity (i.e., \>30 minutes \[min\] per day) or contact sports within 48 hours of the first dose of the study drug or during the study.
• Have a history of relevant drug and/or food allergies (i.e., allergy to drugs with the same class effect as vorasidenib or any excipients, or any significant food allergy).
• Have received study drug in another investigational study within 30 days of dosing.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead

Study Sites (1)

American Research Corporation

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Interventions

vorasidenib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2022
• First Posted: January 6, 2023
• Study Start: March 14, 2023
• Primary Completion: July 18, 2023
• Study Completion: July 18, 2023
• Last Updated: February 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

US (1)