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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01353898
First received: May 12, 2011
Last updated: January 6, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
HIV-1 Infection
Drug: MK-1972
Drug: Placebo to MK-1972
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1972 in HIV-1 Infected Patients

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) [ Time Frame: From consent to 14 days after the last dose (up to Day 24) ] [ Designated as safety issue: Yes ]
    An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an adverse event.

  • Change From Baseline to Day 10 in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Due to Treatment With MK-1972 or Placebo [ Time Frame: Baseline and Day 10 (24 hours post-dose) ] [ Designated as safety issue: No ]
    Blood was collected at baseline and on Day 10, and the plasma concentration for HIV-1 RNA was determined using the Abbott RealTime HIV assay.


Secondary Outcome Measures:
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Plasma concentration of MK-1972 was determined from blood collected from HIV-1 infected participants on Day 10 : pre-dose up to 24 hours post-dose in order to determine the AUC0-24hrs.


Enrollment: 12
Study Start Date: June 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-1972 50 mg once daily (Part I)
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)
Drug: MK-1972
MK-1972 will be supplied as 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Experimental: MK-1972 200 mg once daily (Part I)
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)
Drug: MK-1972
MK-1972 will be supplied as 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Experimental: MK-1972 800 mg once daily (Part I)
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)
Drug: MK-1972
MK-1972 will be supplied as 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Experimental: MK-1972 25 mg twice daily (Part I)
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)
Drug: MK-1972
MK-1972 will be supplied as 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Experimental: MK-1972 100 mg twice daily (Part I)
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)
Drug: MK-1972
MK-1972 will be supplied as 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Placebo Comparator: Placebo twice daily (Part I)
Ten capsules containing placebo were taken orally, twice per day for 10 days (Part I)
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Experimental: MK-1972 800 mg twice daily (Part II)
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)
Drug: MK-1972
MK-1972 will be supplied as 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days
Placebo Comparator: Placebo twice daily (Part II)
Ten capsules containing placebo were taken orally, twice per day for 10 days (Part II)
Drug: Placebo to MK-1972
Placebo will be supplied as matching 25 and 100 mg capsules, and will be given orally, at a dose dependent on the treatment arm; participants will take ten capsules (active drug and/or placebo) once or twice per day for 10 days

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353898

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01353898     History of Changes
Other Study ID Numbers: 1972-003  2011-000071-14 
Study First Received: May 12, 2011
Results First Received: January 6, 2016
Last Updated: January 6, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2016