MK-8507 in Participants With Mild or Moderate Hepatic Impairment (MK-8507-014)
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate pharmacokinetics (PK) and safety of a single oral dose of MK-8507 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Panel A: Mild HI Participants with mild HI receive a single oral dose of MK-8507 400 mg on Day 1. |
Drug: MK-8507
Four MK-8507 100 mg tablets (total dose 400 mg) taken by mouth.
|
| Experimental: Panel B: Moderate HI Participants with moderate HI receive a single oral dose of MK-8507 400 mg on Day 1. |
Drug: MK-8507
Four MK-8507 100 mg tablets (total dose 400 mg) taken by mouth.
|
| Active Comparator: Panel C: Healthy Controls Healthy matched control participants receive a single oral dose of MK-8507 400 mg on Day 1. |
Drug: MK-8507
Four MK-8507 100 mg tablets (total dose 400 mg) taken by mouth.
|
Outcome Measures
Primary Outcome Measures
- Area Under the Plasma Concentration-Time Curve from Dosing to Infinity (AUC0-∞) of MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The AUC0-∞ of MK-8507 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 MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The AUC0-last of MK-8507 will be determined in participants with mild or moderate HI and healthy controls.
- Maximum Plasma Concentration (Cmax) of MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The Cmax of MK-8507 will be determined in participants with mild or moderate HI and healthy controls.
- Time to Maximum Plasma Concentration (Tmax) of MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The Tmax of MK-8507 will be determined in participants with mild or moderate HI and healthy controls.
- Apparent Plasma Terminal Half-life (t½) of MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The t½ of MK-8507 will be determined in participants with mild or moderate HI and healthy controls.
- Apparent Total Clearance from Plasma After Oral Administration (CL/F) of MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The CL/F of MK-8507 will be determined in participants with mild or moderate HI and healthy controls.
- Apparent Volume of Distribution during Terminal Phase (Vz/F) of MK-8507 [Predose and 1, 2, 4, 6, 8, 12, 24, 48, 96, 120, 168, 240, 336, and 504 hours postdose]
The Vz/F of MK-8507 will be determined in participants with mild or moderate HI and healthy controls.
Secondary Outcome Measures
- 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.
Eligibility Criteria
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
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Is not in sufficient health
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Is institutionalized/mentally or legally incapacitated
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Is positive for human immunodeficiency virus (HIV)-1 or HIV-2
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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
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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
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8507-014
- MK-8507-014