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

Study Overview
=================
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.

Official Title
-----------------
A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1972 in HIV-1 Infected Patients

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Drug: MK-1972
* Drug: Placebo to MK-1972


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-1972 50 mg once daily (Part I)<br>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<br>* 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<br>Drug: Placebo to MK-1972<br>* 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<br>|
| Experimental: MK-1972 200 mg once daily (Part I)<br>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<br>* 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<br>Drug: Placebo to MK-1972<br>* 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<br>|
| Experimental: MK-1972 800 mg once daily (Part I)<br>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<br>* 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<br>Drug: Placebo to MK-1972<br>* 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<br>|
| Experimental: MK-1972 25 mg twice daily (Part I)<br>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<br>* 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<br>Drug: Placebo to MK-1972<br>* 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<br>|
| Experimental: MK-1972 100 mg twice daily (Part I)<br>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<br>* 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<br>Drug: Placebo to MK-1972<br>* 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<br>|
| Placebo Comparator: Placebo twice daily (Part I)<br>Ten capsules containing placebo were taken orally, twice per day for 10 days (Part I) | Drug: Placebo to MK-1972<br>* 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<br>|
| Experimental: MK-1972 800 mg twice daily (Part II)<br>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<br>* 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<br>Drug: Placebo to MK-1972<br>* 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<br>|
| Placebo Comparator: Placebo twice daily (Part II)<br>Ten capsules containing placebo were taken orally, twice per day for 10 days (Part II) | Drug: Placebo to MK-1972<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) | 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. | From consent to 14 days after the last dose (up to Day 24) | 
| Change From Baseline to Day 10 in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Due to Treatment With MK-1972 or Placebo | 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. | Baseline and Day 10 (24 hours post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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 |