Study of MK-1972 in Human Immunodeficiency Virus (HIV)-1 Infected Participants Who Have Not Previously Received Antiretroviral Therapy (MK-1972-003)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: HIV-1 Infection

Treatments: Drug: MK-1972; Drug: Placebo to MK-1972

Study type: Interventional

Funder types: Industry

Identifiers

NCT01353898

1972-003

2011-000071-14 (EudraCT Number)

Details and patient eligibility

About

This is a two part study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MK-1972 in participants with HIV-1 infections. In Part 1, participants will be randomized to receive MK-1972 (at one of 5 different dose levels given once or twice per day) or placebo. Part II will begin after the results of Part I are known; participants will be randomized to receive MK-1972 (only one dose level, twice per day) or placebo. The primary hypotheses are that MK-1972 at the studied doses is safe and well tolerated in HIV-1 infected males; and that MK-1972 has superior antiretroviral activity compared to placebo.

Enrollment: 12 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Stable baseline health.
• Appropriate use of contraception; condom protection with pregnant partners.
• Documented HIV-1 positive
• Anti-retroviral therapy (ART)-naïve, defined as having never received any antiretroviral agent or ≤30 consecutive days of an investigational antiretroviral agent, excluding an integrase inhibitor, or ≤60 consecutive days of combination ART excluding an integrase inhibitor.
• No investigational agent or licensed ART within 30 days of study drug administration.
• Diagnosis of HIV-1-infection ≥ 3 months prior to screening.

Exclusion Criteria

• History of stroke, chronic seizures, or major neurological disorder.
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, or genitourinary abnormalities or diseases.
• History of clinically significant neoplastic disease.
• Use of any immune therapy agents or immunosuppressive therapy within 1 month prior to treatment in this study.
• Requirement for chronic daily prescription medications.
• Current (active) diagnosis of acute hepatitis due to any cause.
• 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.
• Positive Hepatitis B surface antigen.
• Refusal to stop using any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals), until the post-study visit.
• Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day.
• Consumption of excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day.
• Smoker of more than 10 cigarettes/day unwilling to restrict smoking to ≤10 cigarettes per day.
• Major surgery, donation or loss of 1 unit of blood (approximately 500 mL) or participation in another investigational study within 4 weeks prior to screening.
• History of significant multiple and/or severe allergies (including latex allergy), or an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
• Current regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year. Participants with a positive cannabis test with no evidence of drug-dependency may be enrolled at the discretion of the investigator.
• History of hepatic or gallbladder disease or history of clinically significant abnormalities in liver function tests, or history of Gilbert's Syndrome, or history of elevated unconjugated bilirubin.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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12 participants in 8 patient groups, including a placebo group

MK-1972 50 mg once daily (Part I)

Experimental group

Description:

Ten capsules containing a total daily dose of 50 mg MK-1972 or placebo were taken orally, once per day for 10 days (Part I)

Treatment:

Drug: MK-1972

Drug: Placebo to MK-1972

MK-1972 200 mg once daily (Part I)

Experimental group

Description:

Ten capsules containing a total daily dose of 200 mg MK-1972 or placebo were taken orally, once per day for 10 days (Part I)

Treatment:

Drug: MK-1972

Drug: Placebo to MK-1972

MK-1972 800 mg once daily (Part I)

Experimental group

Description:

Ten capsules containing a total daily dose of 800 mg MK-1972 or placebo were taken orally, once per day for 10 days (Part I)

Treatment:

Drug: MK-1972

Drug: Placebo to MK-1972

MK-1972 25 mg twice daily (Part I)

Experimental group

Description:

Ten capsules containing a total daily dose of 25 mg MK-1972 or placebo were taken orally, twice per day for 10 days (Part I)

Treatment:

Drug: MK-1972

Drug: Placebo to MK-1972

MK-1972 100 mg twice daily (Part I)

Experimental group

Description:

Ten capsules containing a total daily dose of 100 mg MK-1972 or placebo were taken orally, twice per day for 10 days (Part I)

Treatment:

Drug: MK-1972

Drug: Placebo to MK-1972

Placebo twice daily (Part I)

Placebo Comparator group

Description:

Ten capsules containing placebo were taken orally, twice per day for 10 days (Part I)

Treatment:

Drug: Placebo to MK-1972

MK-1972 800 mg twice daily (Part II)

Experimental group

Description:

Ten capsules containing a total daily dose of 800 mg MK-1972 or placebo were taken orally, twice per day for 10 days (Part II)

Treatment:

Drug: MK-1972

Drug: Placebo to MK-1972

Placebo twice daily (Part II)

Placebo Comparator group

Description:

Ten capsules containing placebo were taken orally, twice per day for 10 days (Part II)

Treatment:

Drug: Placebo to MK-1972