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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV-1 Infection

Treatments: Drug: Ulonivirine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02174159

2014-000660-18 (EudraCT Number)

8507-003

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Panel A: Ulonivirine 600 mg

Experimental group

Description:

Single oral dose of ulonivirine 600 mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast

Treatment:

Drug: Ulonivirine

Panel B: Ulonivirine 150 mg

Experimental group

Description:

Single oral dose of ulonivirine 150 mg (supplied as 10 mg and 100 mg tablets) administered after an overnight fast

Treatment:

Drug: Ulonivirine

Panel C: Ulonivirine <=600 mg

Experimental group

Description:

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.

Treatment:

Drug: Ulonivirine