Hepatic Insufficiency
Conditions
Brief summary
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.
Interventions
DRUGUlonivirine
Four ulonivirine 100 mg tablets (total dose 400 mg) taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution during Terminal Phase (Vz/F) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The Vz/F of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
| Area Under the Plasma Concentration-Time Curve from Dosing to Infinity (AUC0-∞) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The AUC0-∞ of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
| Area Under the Plasma Concentration-Time Curve from Dosing to Last Measurable Concentration (AUC0-last) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The AUC0-last of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
| Maximum Plasma Concentration (Cmax) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The Cmax of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
| Time to Maximum Plasma Concentration (Tmax) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The Tmax of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
| Apparent Plasma Terminal Half-life (t½) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The t½ of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
| Apparent Total Clearance from Plasma After Oral Administration (CL/F) of Ulonivirine | Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose | The CL/F of ulonivirine will be determined in participants with mild or moderate HI and healthy controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with an Adverse Event (AE) | Up to 21 days | 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. |
Outcome results
None listed