Single-Dose Islatravir in Moderate Hepatic Impairment (MK-8591-030)
Study Details
Study Description
Brief Summary
This is an open-label, single-dose study of the plasma pharmacokinetics (PK), safety, and tolerability of islatravir (ISL, MK-8591), and the intracellular PK of ISL triphosphate (ISL-TP) in male and female adult participants with moderate hepatic impairment and in healthy matched control participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Moderate Hepatic Impairment Participants receive a single dose of ISL 60 mg. |
Drug: Islatravir
Two ISL 30 mg capsules taken by mouth.
Other Names:
|
| Experimental: Healthy Controls Participants receive a single dose of ISL 60 mg. |
Drug: Islatravir
Two ISL 30 mg capsules taken by mouth.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area Under the Curve from Dosing to Infinity (AUC0-∞) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The AUC0-∞ of ISL in plasma will be determined in each arm.
- Area Under the Curve from Dosing to Last Measurable Concentration (AUC0-last) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The AUC0-last of ISL in plasma will be determined in each arm.
- Maximum Concentration (Cmax) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The Cmax of ISL in plasma will be determined in each arm.
- Time to Maximum Concentration (Tmax) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The Tmax of ISL in plasma will be determined in each arm.
- Apparent Terminal Half-Life (t½) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The t½ of ISL in plasma will be determined in each arm.
- Apparent Total Clearance of (CL/F) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The CL/F of ISL in plasma will be determined in each arm.
- Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma [Predose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours postdose]
The Vz/F of ISL in plasma will be determined in each arm.
Secondary Outcome Measures
- Percentage of Participants With ≥1 Adverse Event (AE) [Up to 28 days]
The percentage of participants experiencing an AE will be determined in each arm.
- Percentage of Participants Discontinuing Treatment due to AE(s) [Up to 1 day]
The percentage of participants discontinuing study therapy due to AE(s) will be determined in each arm.
- AUC0-∞ of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMCs) [Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours postdose]
The intracellular AUC0-∞ of ISL-TP in PBMCs will be determined in each arm.
- AUC0-last of ISL-TP in PBMCs [Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours postdose]
The intracellular AUC0-last of ISL-TP in PBMCs will be determined in each arm.
- Cmax of ISL-TP in PBMCs [Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours postdose]
The intracellular Cmax of ISL-TP in PBMCs will be determined in each arm.
- Concentration 24 Hours Postdose (C24) of ISL-TP in PBMCs [24 hours postdose]
The intracellular C24 of ISL-TP in PBMCs will be determined in each arm.
- Concentration 168 Hours Postdose (C168) of ISL-TP in PBMCs [168 hours postdose]
The intracellular C168 of ISL-TP in PBMCs will be determined in each arm.
- Concentration 672 Hours Postdose (C672) of ISL-TP in PBMCs [672 hours postdose]
The intracellular C672 of ISL-TP in PBMCs will be determined in each arm.
- Tmax of ISL-TP in PBMCs [Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours postdose]
The intracellular Tmax of ISL-TP in PBMCs will be determined in each arm.
- t½ of ISL-TP in PBMCs [Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours postdose]
The intracellular t½ of ISL-TP in PBMCs will be determined in each arm.
Eligibility Criteria
Criteria
Inclusion Criteria:
Healthy Control Participants:
-
Is in good health based on medical history, physical examination, vital sign (VS) measurements and electrocardiograms (ECGs) performed prior to randomization
-
Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of the initial dose of study drug.
-
Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2
Hepatic Impairment Participants:
-
Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
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Has a score on the Child-Pugh scale ranging from 7 to 9 (moderate hepatic insufficiency) at screening
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With the exception of hepatic impairment, is in generally good health
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Has a BMI ≥ 18.5 and ≤ 40 kg/m2
Healthy and Hepatic Impairment Participants:
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Males : uses contraception according to local regulations
-
Females: is not pregnant or breastfeeding and one of the following applies:
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Is not a woman of childbearing potential (WOCBP) OR
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Is a WOCBP and uses an acceptable contraceptive method
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A WOCBP with negative highly sensitive pregnancy test within 24 hours of study intervention
Exclusion Criteria:
-
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, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years
-
Has a history of cancer (malignancy)
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Has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food
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Has known hypersensitivity to the active substance or any of the excipients of the study drug
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Is positive for hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or HIV-2
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Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
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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 study drug administration, throughout the study, until the poststudy visit
-
Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
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Has a QTc interval >470 for males or >480 ms for females, has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking concomitant medications that prolong the QT/QTc interval
-
Is not considered low risk of having HIV infection
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Is a smoker or user of electronic cigarettes and/or has used nicotine or nicotine-containing products (eg, nicotine patch) within 3 months of screening
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Consumes greater than 3 glasses of alcoholic beverages per day
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Consumes more than 6 caffeinated beverages per day
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Is a regular user of illicit drugs or has a history of drug abuse within 2 years
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Presents any concern to the investigator regarding safe study participation
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Is unwilling to comply with study restrictions
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Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Pharmacology of Miami ( Site 0001) | Miami | Florida | United States | 33014 |
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.- 8591-030
- MK-8591-030