Clinical trial NCT01353898: Study of MK-1972 in Human Immunodeficiency Virus (HIV)-1 Infected Participants Who Have Not Previously Received Antiretroviral Therapy (MK-1972-003)
Official title: A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1972 in HIV-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-05-16
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs)
timeFrame: From consent to 14 days after the last dose (up to Day 24)
measure: Change From Baseline to Day 10 in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Due to Treatment With MK-1972 or Placebo
timeFrame: Baseline and Day 10 (24 hours post-dose)
Secondary outcomes:
measure: The Area Under the Curve From 0-24 Hours (AUC0-24hrs) on Day 10 for Plasma Concentration of MK-1972 in Participants With HIV-1 Infection
timeFrame: Day 10: pre-dose, and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: