MK-8510 Monotherapy for the Treatment of Anti-retroviral naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants (MK-8510-002)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and anti-retroviral activity of MK-8510 monotherapy in anti-retroviral-naïve HIV-1 infected participants.

Official Title
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A Single-dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-retroviral Activity of MK-8510 Monotherapy in Anti-retroviral-naïve HIV-1 Infected Participants

Conditions
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HIV-1, Human Immunodeficiency Virus 1, Immunodeficiency Virus Type 1, Human, Human Immunodeficiency Virus Type 1

Intervention / Treatment
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* Drug: MK-8510


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has HIV-1 infection, and is in good health based on medical history, physical examination, vital signs (VS) measurements, and laboratory safety tests. Has documented HIV-1 positive, as determined by a positive enzyme-linked immunosorbent assay (ELISA) or real-time quantitative polymerase chain reaction (QT-PCR) with confirmation (eg, Western Blot). Is anti-retroviral therapy (ART)-naïve, which is defined as: Having never received any anti-retroviral agent; or ART-experienced but has not received any ART for HIV-1 infection within 60 days; or Has received pre-exposure prophylaxis (PrEP) treatment prior to diagnosis of HIV-infection but has not received any PrEP within 30 days. Is willing to receive no other ART prior to Day 11 post-dose of the study. Has a body mass index (BMI) ≤35 kg/m2. Exclusion Criteria: Has acute (primary) HIV-1 infection. Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Has remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma). Is mentally or legally incapacitated or has significant emotional problems. Has history of cancer (malignancy). Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e, systemic allergic reaction) to prescription or nonprescription drugs or food. Has positive hepatitis B surface antigen (HBsAg). Has a history of chronic hepatitis C unless there has been documented cure and/or participant with a positive serologic test for hepatitis C virus (HCV) has a negative HCV viral load (VL). 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. Has participated in another investigational study within 4 weeks. Has a clinically significant abnormality on the electrocardiogram (ECG) performed at the pre-study visit. Has been committed to an institution by way of official or judicial order. Is under the age of legal consent or not capable of giving consent. Does not agree to follow the smoking restrictions as defined by the clinical research unit (CRU). 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. 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. Is a regular user of any illicit drugs (not including cannabis) or has an history of drug (including alcohol) abuse within approximately 12 months.

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: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A: MK-8510 at dose level 1<br>Single oral dose of MK-8510 administered at dose level 1 (≤1800 mg) following a 10-hour fast. Dose level 1 shall not exceed 1800 mg. | Drug: MK-8510<br>* Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.<br>|
| Experimental: Panel B: MK-8510 at dose level 2<br>Single oral dose of MK-8510 administered at dose level 2 (≤2200 mg) following a 10-hour fast. Dose level 2 shall not exceed 2200 mg. | Drug: MK-8510<br>* Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.<br>|
| Experimental: Panel C: MK-8510 at dose level 3<br>Single oral dose of MK-8510 administered at dose level 3 (≤2200 mg) following a 10-hour fast. Dose level 3 shall not exceed 2200 mg. | Drug: MK-8510<br>* Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.<br>|
| Experimental: Panel D: MK-8510 at dose level 4<br>Single oral dose of MK-8510 administered at dose level 4 (≤2200 mg) following a 10-hour fast. Dose level 4 shall not exceed 2200 mg. | Drug: MK-8510<br>* Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.<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 plasma HIV-RNA will be measured based on a longitudinal data analysis model containing fixed effects for dose level, and dose level by time interaction, and a random effect of MK-8510 (prodrug). The change from baseline for each dose level at 168-hours post baseline will be estimated from this model. | Baseline and 168 hours post-dose | 
| Percentage of Participants Who Experience an Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to 36 days | 
| Percentage of Participants Who Discontinued from Study Due to an Adverse Event (AE) | The percentage of participants who discontinue study due to an AE will be presented. | Up to 36 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve of MK-8558 From Time 0 to 168 Hours (AUC0-168 hr) | The AUC0-168 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168 hours post-dose. | At protocol specific timepoints up to 168 hours post-dose | 
| Area Under the Concentration-Time Curve of MK-8558 From Time 0 to last (AUC0-last) | AUC0-last of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose | 
| Concentration at 168 Hours Post-dose (C168) of MK-8558 | C168hr of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated. | 168 hours post-dose | 
| Maximum Concentration (Cmax) of MK-8558 | Cmax of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose | 
| Time to Maximum Plasma Concentration (Tmax) of MK-8558 | Tmax of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose | 
| Half Life (t1/2) of MK-8558 | t1/2 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose | 
| Apparent Plasma Clearance of Drug After Extravascular Administration (CL/F) of MK-8558 | CL/F of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose | 
| Apparent Volume of Distribution in the Terminal State After Extravascular Administration (Vz/F) of MK-8558 | Vz/F of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose | 
| Terminal t1/2 of MK-8558 | Terminal t1/2 of MK-8558 (active drug) after administration of MK-8510 (prodrug) in plasma will be calculated pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose. | At protocol specific time points up to 504 hours post-dose |