Ulonivirine (MK-8507) in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate pharmacokinetics (PK) and safety of a single oral dose of ulonivirine in participants with mild or moderate hepatic impairment (HI). It is hypothesized that the area under the plasma concentration-time curve from dosing to (extrapolated) infinity (AUC0-∞) in participants with mild or moderate HI is similar to that of healthy control participants.

Official Title
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An Open-Label, Single-Dose Clinical Study to Evaluate Pharmacokinetics of MK-8507 in Participants With Mild or Moderate Hepatic Impairment.

Conditions
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Hepatic Insufficiency

Intervention / Treatment
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* Drug: Ulonivirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild and Moderate HI (Panels A and B): Has a diagnosis of chronic (>6 months), stable HI with features of cirrhosis due to any etiology (stability of hepatic disease should correspond to no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) Healthy Controls (Panel C): Is in good health All Participants (Panels A to C): Has a body mass index (BMI) ≥18.5 and ≤40 kg/m^2, inclusive If male, uses contraception in accordance with local regulations If female, is not pregnant or breastfeeding and one of the following applies: 1) is not a woman of childbearing potential (WOCBP), or 2) is a WOCBP and is abstinent/uses acceptable contraception, has a negative highly sensitive pregnancy test within 24 hours of receiving study intervention, and provides medical/menstrual/recent sexual history for review by the investigator Exclusion Criteria: Mild and Moderate HI (Panels A and B): Has a history of any illness that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study Is not in sufficient health Is institutionalized/mentally or legally incapacitated Is positive for human immunodeficiency virus (HIV)-1 or HIV-2 Has received antiviral and/or immune modulating therapy for hepatitis B virus (HBV) or hepatitis C virus (HCV) within 90 days prior to study start Is taking medication for a chronic condition and has not been on a stable regimen for ≥ 1 month Healthy Controls (Panel C): Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases Is mentally or legally incapacitated Is positive for hepatitis B virus surface antigen (HBsAg), hepatitis C antibodies, HIV-1, or HIV-2 Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to first dose of study drug All Participants (Panel A to C): Has a history of cancer (malignancy) Has a history of significant multiple and/or severe allergies Has known hypersensitivity to the active substance or any of the excipients of the study drug Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A: Mild HI<br>Participants with mild HI receive a single oral dose of ulonivirine 400 mg on Day 1. | Drug: Ulonivirine<br>* Four ulonivirine 100 mg tablets (total dose 400 mg) taken by mouth.<br>* Other names: MK-8507;|
| Experimental: Panel B: Moderate HI<br>Participants with moderate HI receive a single oral dose of ulonivirine 400 mg on Day 1. | Drug: Ulonivirine<br>* Four ulonivirine 100 mg tablets (total dose 400 mg) taken by mouth.<br>* Other names: MK-8507;|
| Active Comparator: Panel C: Healthy Controls<br>Healthy matched control participants receive a single oral dose of ulonivirine 400 mg on Day 1. | Drug: Ulonivirine<br>* Four ulonivirine 100 mg tablets (total dose 400 mg) taken by mouth.<br>* Other names: MK-8507;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve from Dosing to Infinity (AUC0-∞) of Ulonivirine | The AUC0-∞ of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 
| Area Under the Plasma Concentration-Time Curve from Dosing to Last Measurable Concentration (AUC0-last) of Ulonivirine | The AUC0-last of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 
| Maximum Plasma Concentration (Cmax) of Ulonivirine | The Cmax of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 
| Time to Maximum Plasma Concentration (Tmax) of Ulonivirine | The Tmax of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 
| Apparent Plasma Terminal Half-life (t½) of Ulonivirine | The t½ of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 
| Apparent Total Clearance from Plasma After Oral Administration (CL/F) of Ulonivirine | The CL/F of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 
| Apparent Volume of Distribution during Terminal Phase (Vz/F) of Ulonivirine | The Vz/F of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to 21 days |