Evaluation of Safety, Tolerability, Pharmacokinetics, and Antiretroviral Activity of Ulonivirine (MK-8507) in Human Immunodeficiency Virus (HIV-1)-Infected Participants (MK-8507-003)

Study Overview
=================
Brief Summary
-----------------
The study will evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of a single dose of ulonivirine in antiretroviral therapy (ART)-naive, HIV-1 infected participants. The hypothesis tested in the study is that at a safe and well-tolerated dose, ulonivirine has superior antiretroviral activity to a historical placebo control, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours postdose.

Official Title
-----------------
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-8507 in HIV-1 Infected Patients

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

Intervention / Treatment
-----------------
* Drug: Ulonivirine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male, or non-pregnant and non-breastfeeding female, or postmenopausal or surgically sterile female (confirmed with medical records, examination, or laboratory test). Male participants with female partner of childbearing potential agrees to use a medically acceptable method of contraception during the study and 90 days after receiving study drug. Body mass index <=35 kg/m^2 Other than HIV infection, baseline health judged to be stable at screening and/or prior to administration of study drug No clinically-significant electrocardiogram abnormality Documented to be HIV-1 positive as determined by a positive enzyme-linked immunosorbent assay (ELISA) or quantitative polymerase chain reaction (PCR) result with confirmation Has a screening plasma Cluster of Differentiation (CD4) T-cell count of >200 /mm^3 Has a plasma HIV-1 RNA >= 10,000 copies/mL within 30 days before administration of study drug ART-naive, defined as never having received any ART agent, or have received <=30 consecutive days of an investigational ART agent, excluding non-nucleoside reverse transcriptase inhibitors (NNRTIs), or have received <=60 consecutive days of combination ART, excluding NNRTIs Has not received an investigational agent or licensed ART within 30 days of study drug administration Diagnosed with HIV-1 infection >=3 months before screening Willing to receive no other ART for the duration of the study Has no evidence of mutations conferring resistance to NNRTIs at screening Exclusion Criteria: Mentally or legally institutionalized or incapacitated, has significant emotional problems, or has a history of clinically significant psychiatric disorder History of clinically significant and not stably controlled abnormalities or diseases History of cancer, with the exceptions of 1) adequately-treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, 2) other malignancies which have been successfully treated >=10 years before screening, or 3) participants who are highly unlikely to sustain a recurrence for the duration of the study History of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to drugs or food Positive for hepatitis B surface antigen History of chronic hepatitis C virus (HCV) unless there has been a documented cure or a negative HCV viral load Had major surgery, or donated or lost >=1 unit ( 500 mL) of blood within 4 weeks before screening Participated in another investigational trial within 4 weeks before administration of study drug Unable to refrain from or anticipates the use of any medication beginning 4 weeks before administration of study drug and throughout the trial. Certain medications are permitted. Consumes >3 glasses of alcoholic beverages per day (1 glass is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of distilled spirits). Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator. Consumes >10 cigarettes per day and is unwilling to restrict smoking to <=10 cigarettes per day Regular user of any illicit drugs or has a history of drug abuse (including alcohol) within 2 years Has an immediate family member who is investigational site or sponsor staff directly involved with the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A: Ulonivirine 600 mg<br>Single oral dose of ulonivirine 600 mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast | Drug: Ulonivirine<br>* MK-8507 administered as a single oral dose<br>* Other names: MK-8507;|
| Experimental: Panel B: Ulonivirine 150 mg<br>Single oral dose of ulonivirine 150 mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast | Drug: Ulonivirine<br>* MK-8507 administered as a single oral dose<br>* Other names: MK-8507;|
| Experimental: Panel C: Ulonivirine <=600 mg<br>Single oral dose of ulonivirine <=600 mg mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast. Inclusion of Panel C in the study, and the dose selected, will be decided pending evaluation of results for Panels A and B. | Drug: Ulonivirine<br>* MK-8507 administered as a single oral dose<br>* Other names: MK-8507;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Plasma HIV-1 RNA |  | 168 hours (7 days) postdose | 
| Number of Participants with One or More Adverse Experiences |  | Up to 21 days postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve of Ulonivirine (AUC0-168hr) |  | Up to 168 hours postdose | 
| Maximum Plasma Concentration of Ulonivirine (Cmax) |  | Up to 336 hours postdose | 
| Time of Maximum Plasma Concentration of Ulonivirine (Tmax) |  | Up to 336 hours postdose | 
| Plasma Concentration of Ulonivirine at 168 Hours Postdose (C168hr) |  | 168 hours postdose | 
| Plasma Concentration of Ulonivirine at 336 Hours Postdose (C336hr) |  | 336 hours postdose | 
| Apparent Terminal Half-Life (T1/2) of Plasma Ulonivirine |  | Up to 336 hours postdose |