MK-8527 Single-Dose Trial in HIV-1 Infected Participants (MK-8527-004)

Study Overview
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Brief Summary
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This is a single-dose clinical study to evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-8527 in antiretroviral therapy (ART)-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. The primary hypothesis is that, at a dose that is safe and generally well tolerated, MK-8527 will have antiretroviral activity as measured by a reduction from baseline in plasma HIV-1 ribonucleic acid (RNA) of ≥1.0 log10 copies/mL.

Official Title
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A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8527 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Participants

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: MK-8527


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is in good health other than HIV-1 infection Is documented HIV-1 positive Is ART-naïve, which is defined as not having received any marketed antiretroviral agent for treatment of HIV-1 infection (prior use of an ART for PrEP or investigational therapy is permitted if the last dose was ≥30 days prior to study drug administration) Is willing to receive no other ART for the monitoring period of this study If male, agrees to the following during the intervention period and for at least 8 weeks after the last dose of study intervention: abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent; or uses contraception unless confirmed to be azoospermic A female participant is eligible to participate if not pregnant or breastfeeding, and at least one of the following applies: is not a woman of childbearing potential (WOCBP); or is a WOCBP and uses a highly effective contraceptive, has a negative pregnancy test within 24 hours of study intervention administration, abstains from breastfeeding for at least 56 days after study intervention, and has medical/menstrual/recent sexual activity reviewed by the investigator to decrease the risk of an early undetected pregnancy Exclusion Criteria: Has a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), 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) other than adequately treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other malignancy that has been successfully treated and unlikely to recur for the duration of the study in the opinion of the investigator Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food Is positive for hepatitis B surface antigen Has a history of chronic hepatitis C unless there has been documented cure Has had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit 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 administration of the initial dose of study intervention, 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 Is an excessive smoker (ie, more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day Consumes greater than 3 servings of alcoholic beverages (1 serving is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day. Participants who consume 4 servings of alcoholic beverages per day may be enrolled at the discretion of the investigator Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day Has a positive urine drug screen (except for cannabis or benzodiazepines, for which there is a current prescription from a licensed medical provider) at screening and/or predose; rechecks are allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A: MK-8527 1.0 mg<br>Participants receive a single oral dose of MK-8527 1.0 mg. | Drug: MK-8527<br>* MK-8527 capsule taken by mouth.<br>|
| Experimental: Panel B: MK-8527 0.5 mg<br>Participants receive a single oral dose of MK-8527 0.5 mg. | Drug: MK-8527<br>* MK-8527 capsule taken by mouth.<br>|
| Experimental: Panel C: MK-8527 0.25 mg<br>Participants receive a single oral dose of MK-8527 0.25 mg. | Drug: MK-8527<br>* MK-8527 capsule taken by mouth.<br>|
| Experimental: Panel D: MK-8527 0.25 mg<br>Participants receive a single oral dose of MK-8527 0.25 mg. | Drug: MK-8527<br>* MK-8527 capsule taken by mouth.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in plasma HIV-1 ribonucleic acid (RNA) | The change from baseline in HIV-1 RNA will be determined. | Baseline and 168 hours postdose on Day 1 | 
| Number of participants experiencing ≥1 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 28 days | 
| Number of participants discontinuing from study due to an 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 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve from Predose to 168 hours postdose (AUC0-168) of MK-8527 Triphosphate (MK-8527-TP) in Peripheral Blood Mononuclear Cells (PBMCs) | Intracellular MK-8527-TP AUC0-168 will be determined in PBMCs. | Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose | 
| Area Under the Concentration-Time Curve from Predose to Last Measurable Concentration (AUC0-last) of MK-8527-TP in PBMCs | Intracellular MK-8527-TP AUC0-last will be determined in PBMCs. | Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose | 
| Area Under the Concentration-Time Curve from Predose to Infinity (AUC0-inf) of MK-8527-TP in PBMCs | Intracellular MK-8527-TP AUC0-inf will be determined in PBMCs. | Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose | 
| Time to Maximum Concentration (Tmax) of MK-8527-TP in PBMCs | Intracellular MK-8527-TP Tmax will be determined in PBMCs. | Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose | 
| Maximum Concentration (Cmax) of MK-8527-TP in PBMCs | Intracellular MK-8527-TP Cmax will be determined in PBMCs. | Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose | 
| Concentration at 168 Hours Postdose (C168) of MK-8527-TP in PBMCs | C168 of MK-8527-TP will be determined in PBMCs. | 168 hours postdose | 
| Apparent terminal half-life (t½) of MK-8527-TP in PBMCs | The apparent t½ of MK-8527-TP will be determined in PBMCs. | Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose | 
| AUC0-last of MK-8527 in Plasma | The AUC0-last of MK-8527 will be determined in plasma. | Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | 
| AUC0-inf of MK-8527 in Plasma | The AUC0-inf of MK-8527 will be determined in plasma. | Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | 
| Tmax of MK-8527 in Plasma | The Tmax of MK-8527 will be determined in plasma. | Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | 
| Cmax of MK-8527 in Plasma | The Cmax of MK-8527 will be determined in plasma. | Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | 
| Clast of MK-8527 in Plasma | The Clast of MK-8527 will be determined in plasma. | Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | 
| Apparent t½ of MK-8527 in Plasma | The apparent t½ of MK-8527 will be determined in plasma. | Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | 
| Correlation Between Intracellular C168 of MK-8527-TP in PBMCs and Change from Baseline in Plasma HIV-1 RNA | The correlation between between the C168 of MK-8527-TP in PBMCs and the change from baseline in plasma HIV-1 RNA levels 168 hours after dosing will calculated. | Predose and 168 hours postdose |