Activity of MK-8504 in Anti-retroviral-naïve, Human Immunodeficiency Virus 1 (HIV-1) Infected Participants (MK-8504-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV-1 Infection

Treatments: Drug: MK-8504

Study type: Interventional

Funder types: Industry

Identifiers

NCT03188523

MK-8504-002 (Other Identifier)

2017-000998-37 (EudraCT Number)

8504-002

Details and patient eligibility

About

This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of monotherapy with MK-8504 (a tenofovir pro-drug), in ART-naïve Human Immunodeficiency Virus (HIV)-1 infected participants. The primary hypothesis is that MK-8504, at a dose that is sufficiently safe and well tolerated, has superior antiretroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours post-dose.

Enrollment: 12 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or non-pregnant and non-breast feeding female
• Have a Body Mass Index (BMI) ≤35 kg/m^2
• Other than HIV infection, have stable baseline health based on medical history, physical examination, vital sign measurements, and laboratory safety test
• Is documented HIV-1 positive
• Is diagnosed with HIV-1 infection 3 months prior to screening
• Is ART-naïve
• Has not received an investigational agent or marketed ART within 30 days of study drug administration and is willing to receive no other ART for the duration of this study
• Agree to follow smoking and other trial restrictions

Exclusion criteria

• Is mentally or legally institutionalized / incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years
• Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Has a history of cancer (malignancy)
• Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food
• Is positive for hepatitis B surface antigen
• Has a history of chronic Hepatitis C
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
• Has participated in another investigational trial within 4 weeks or 5 half-lives, whichever is greater, prior to the Day 1 Dosing visit
• Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit
• Consumes greater than 3 glasses of alcoholic beverages or distilled spirits per day
• Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
• Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
• Have clinically significant abnormality on the electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
• Has a positive urine drug screen (except for cannabis) at screening and/or predose, rechecks are allowed

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 4 patient groups

MK-8504 100 mg (Panel A)

Experimental group

Description:

Participants receive a single oral dose of MK-8504 100 mg.

Treatment:

Drug: MK-8504

MK-8504 240 mg (Panel B)

Experimental group

Description:

Participants receive a single oral dose of MK-8504 240 mg.

Treatment:

Drug: MK-8504

MK-8504 ≤240 mg (Panel C)

Experimental group

Description:

Participants receive a single oral dose of MK-8504 ≤240 mg.

Treatment:

Drug: MK-8504

MK-8504 ≤240 mg (Panel D)

Experimental group

Description:

Participants receive a single oral dose of MK-8504 ≤240 mg.

Treatment:

Drug: MK-8504