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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: HIV-1; Immunodeficiency Virus Type 1, Human; Human Immunodeficiency Virus Type 1; Human Immunodeficiency Virus 1
• Intervention / Treatment: Drug: MK-8510

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Having never received any anti-retroviral agent; or
  2. ART-experienced but has not received any ART for HIV-1 infection within 60 days; or
  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: MK-8510 at dose level 1; 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; Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.
Experimental: Panel B: MK-8510 at dose level 2; 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; Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.
Experimental: Panel C: MK-8510 at dose level 3; 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; Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.
Experimental: Panel D: MK-8510 at dose level 4; 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; Single dose of MK-8510 administered as a tablet at a dose up to 2200 mg.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): April 17, 2023
• Primary Completion (Anticipated): February 14, 2024
• Study Completion (Anticipated): February 14, 2024

Study Registration Dates

• First Submitted: January 17, 2023
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Virus Diseases; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
• Other Study ID Numbers: 8510-002; MK-8510-002 (Other Identifier: Merck); 2021-006180-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes