search
Back to results

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

Primary Purpose

Hepatic Impairment

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Vorasidenib
Sponsored by
Institut de Recherches Internationales Servier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Impairment focused on measuring Vorasidenib

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for All Participants: 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. Inclusion Criteria for Healthy Participants Only: Have normal hepatic function. Inclusion Criteria for Participants with Hepatic Impairment Only: 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. Exclusion Criteria for All Participants: 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. Exclusion Criteria for Participants with Hepatic Impairment Only: Have ascites that requires paracentesis every 4 weeks or less frequently. Have evidence of hepatorenal syndrome or hepatic encephalopathy. Have a history of incipient/planned liver transplantation within 6 months of Screening or have received a liver transplant. Have amylase and/or lipase levels ≥3 x upper limit of normal (ULN). Presence of 8 x ULN elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin and international normalized ratio (INR) of 3.5 for the hepatic impaired group.

Sites / Locations

  • American Research CorporationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A: Normal Hepatic Function

Group B: Moderate or Mild Hepatic Impairment

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of Vorasidenib
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Vorasidenib
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-t) for Vorasidenib
AUC From Time 0 Extrapolated to Infinity (AUC0-inf) for Vorasidenib

Secondary Outcome Measures

Apparent Terminal Elimination Half-life (t1/2) of Vorasidenib
Apparent Oral Clearance (CL/F) for Vorasidenib
Apparent Volume of Distribution (Vz/F) of Vorasidenib
Area Under the Unbound Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t,u) for Vorasidenib
Area Under the Unbound Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf,u) for Vorasidenib
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Vorasidenib
Cmax of Metabolite AGI-69460
Tmax of Metabolite AGI-69460
AUC0-t for Metabolite AGI-69460
AUC0-inf for Metabolite AGI-69460
Number of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Number of Participants With Abnormalities in Laboratory Parameters
Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis.
Number of Participants With Abnormalities in Vital Signs
Systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature will be assessed.
Number of Participants With Abnormalities in 12-Lead Electrocardiogram (ECG) Results
Number of Participants With Abnormalities in Physical Examination Findings

Full Information

First Posted
December 30, 2022
Last Updated
April 5, 2023
Sponsor
Institut de Recherches Internationales Servier
search

1. Study Identification

Unique Protocol Identification Number
NCT05674474
Brief Title
A Study of Vorasidenib in Participants With Moderate or Mild Hepatic Impairment and Matched Participants With Normal Hepatic Function
Official Title
A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a 20-mg Dose of Vorasidenib in Subjects With Moderate or Mild Hepatic Impairment and Matched Subjects With Normal Hepatic Function
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2023 (Actual)
Primary Completion Date
August 30, 2023 (Anticipated)
Study Completion Date
August 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Recherches Internationales Servier

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Vorasidenib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A: Normal Hepatic Function
Arm Type
Experimental
Arm Description
Participants with normal hepatic function will receive a single oral dose of 20 mg (2 × 10 mg) vorasidenib tablets on Day 1.
Arm Title
Group B: Moderate or Mild Hepatic Impairment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vorasidenib
Other Intervention Name(s)
S095032, AG-881
Intervention Description
Administered orally as tablets.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-t) for Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
AUC From Time 0 Extrapolated to Infinity (AUC0-inf) for Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Secondary Outcome Measure Information:
Title
Apparent Terminal Elimination Half-life (t1/2) of Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Apparent Oral Clearance (CL/F) for Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Apparent Volume of Distribution (Vz/F) of Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Area Under the Unbound Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t,u) for Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Area Under the Unbound Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf,u) for Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Vorasidenib
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Cmax of Metabolite AGI-69460
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Tmax of Metabolite AGI-69460
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
AUC0-t for Metabolite AGI-69460
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
AUC0-inf for Metabolite AGI-69460
Time Frame
Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose
Title
Number of Participants With Adverse Events (AEs)
Description
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Time Frame
Up to end of study [EOS] (up to approximately 29 days)
Title
Number of Participants With Abnormalities in Laboratory Parameters
Description
Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis.
Time Frame
Up to EOS (up to approximately 29 days)
Title
Number of Participants With Abnormalities in Vital Signs
Description
Systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature will be assessed.
Time Frame
Up to EOS (up to approximately 29 days)
Title
Number of Participants With Abnormalities in 12-Lead Electrocardiogram (ECG) Results
Time Frame
Up to EOS (up to approximately 29 days)
Title
Number of Participants With Abnormalities in Physical Examination Findings
Time Frame
Up to EOS (up to approximately 29 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for All Participants: 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. Inclusion Criteria for Healthy Participants Only: Have normal hepatic function. Inclusion Criteria for Participants with Hepatic Impairment Only: 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. Exclusion Criteria for All Participants: 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. Exclusion Criteria for Participants with Hepatic Impairment Only: Have ascites that requires paracentesis every 4 weeks or less frequently. Have evidence of hepatorenal syndrome or hepatic encephalopathy. Have a history of incipient/planned liver transplantation within 6 months of Screening or have received a liver transplant. Have amylase and/or lipase levels ≥3 x upper limit of normal (ULN). Presence of 8 x ULN elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin and international normalized ratio (INR) of 3.5 for the hepatic impaired group.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Institut de Recherches Internationales Servier, Clinical Studies Department
Phone
+33 1 55 72 60 00
Email
scientificinformation@servier.com
Facility Information:
Facility Name
American Research Corporation
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: sponsored by Servier with a first patient enrolled as of 1 January 2004 onwards for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
IPD Sharing Time Frame
After Marketing Authorisation in EEA or US if the study is used for the approval.
IPD Sharing 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.
IPD Sharing URL
https://clinicaltrials.servier.com/

Learn more about this trial

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

We'll reach out to this number within 24 hrs