A Study of Vorasidenib in Participants With Moderate or Mild Hepatic Impairment and Matched Participants With Normal Hepatic Function
Study Details
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 40 mg vorasidenib in participants with hepatic impairment relative to healthy matched control participants with normal hepatic function.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A: Normal Hepatic Function Participants with normal hepatic function will receive a single oral dose of 40 mg vorasidenib tablets on Day 1. |
Drug: Vorasidenib
Administered orally as tablets.
Other Names:
|
| Experimental: Group B: Moderate or Mild Hepatic Impairment 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 40 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 40 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
Administered orally as tablets.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
- Maximum Observed Unbound Plasma Concentration (Cmax,u) of Vorasidenib [Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose]
- Cmax of Metabolite AGI-69460 [Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose]
- Tmax of Metabolite AGI-69460 [Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose]
- AUC0-t for Metabolite AGI-69460 [Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose]
- AUC0-inf for Metabolite AGI-69460 [Day 1 before dosing (0 hour) and at multiple time points up to 504 hours post-dose]
- Number of Participants With Adverse Events (AEs) [Up to end of study [EOS] (up to approximately 29 days)]
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 [Up to EOS (up to approximately 29 days)]
Clinical laboratory assessments will include hematology, serum chemistry, coagulation, and urinalysis.
- Number of Participants With Abnormalities in Vital Signs [Up to EOS (up to approximately 29 days)]
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 [Up to EOS (up to approximately 29 days)]
- Number of Participants With Abnormalities in Physical Examination Findings [Up to EOS (up to approximately 29 days)]
Eligibility Criteria
Criteria
Inclusion Criteria for All Participants:
-
Have a body mass index of 18 to 40 kilograms per square meter (kg/m^2).
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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.
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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.
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Non-smoker or uses ≤10 cigarettes per day as judged by the investigator.
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Agree to comply with all protocol requirements for the duration of the study.
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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).
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.
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Have a history (within 5 years) or presence of malignancy, except for adequately treated basal cell and squamous cell carcinoma of the skin.
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Have received any vaccine or used any prescription (excluding hormonal birth control and hormone replacement therapy) or over-the-counter medications, including herbal or nutritional supplements, within 30 days before the first dose of the study drug.
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Have a positive test result for hepatitis B surface antigen or antibodies to hepatitis C virus.
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Have a positive test result for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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Have a positive test result for human immunodeficiency virus (HIV) types 1 or 2 antibodies.
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Have used strong cytochrome P450 (CYP)1A2 inhibitors and/or inducers within 14 days, prior to the first dose administration.
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Any drugs known to be strong inducers of CYP3A, CYP2C9, or CYP2C19 enzymes including St. John's Wort and/or, gastric acid-reducing agents (e.g., proton-pump inhibitors, histamine-2 [H2]-receptor antagonists, antacids) for 28 days or 5 drug half-lives (whichever is longer).
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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).
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Have a history of alcoholism or drug abuse within 3 months before Screening or excessive alcohol consumption.
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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.
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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.
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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).
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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.
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Have evidence of hepatorenal syndrome or hepatic encephalopathy.
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Have a history of incipient/planned liver transplantation within 6 months of Screening or have received a liver transplant.
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Institut de Recherches Internationales Servier
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PKH-95032-008