Clinical trial NCT05093972: Ulonivirine (MK-8507) in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014)
Official title: An Open-Label, Single-Dose Clinical Study to Evaluate Pharmacokinetics of MK-8507 in Participants With Mild or Moderate Hepatic Impairment.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Hepatic Insufficiency
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-10-26
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve from Dosing to Infinity (AUC0-∞) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
measure: Area Under the Plasma Concentration-Time Curve from Dosing to Last Measurable Concentration (AUC0-last) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
measure: Apparent Plasma Terminal Half-life (t½) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
measure: Apparent Total Clearance from Plasma After Oral Administration (CL/F) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
measure: Apparent Volume of Distribution during Terminal Phase (Vz/F) of Ulonivirine
timeFrame: Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose
Secondary outcomes:
measure: Percentage of Participants with an Adverse Event (AE)
timeFrame: Up to 21 days
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: