Clinical trial NCT02174159: Evaluation of Safety, Tolerability, Pharmacokinetics, and Antiretroviral Activity of Ulonivirine (MK-8507) in Human Immunodeficiency Virus (HIV-1)-Infected Participants (MK-8507-003)
Official title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiretroviral Activity of MK-8507 in HIV-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-06-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change from Baseline in Plasma HIV-1 RNA
timeFrame: 168 hours (7 days) postdose
measure: Number of Participants with One or More Adverse Experiences
timeFrame: Up to 21 days postdose
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve of Ulonivirine (AUC0-168hr)
timeFrame: Up to 168 hours postdose
measure: Maximum Plasma Concentration of Ulonivirine (Cmax)
timeFrame: Up to 336 hours postdose
measure: Time of Maximum Plasma Concentration of Ulonivirine (Tmax)
timeFrame: Up to 336 hours postdose
measure: Plasma Concentration of Ulonivirine at 168 Hours Postdose (C168hr)
timeFrame: 168 hours postdose
measure: Plasma Concentration of Ulonivirine at 336 Hours Postdose (C336hr)
timeFrame: 336 hours postdose
measure: Apparent Terminal Half-Life (T1/2) of Plasma Ulonivirine
timeFrame: Up to 336 hours postdose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Schurmann D, Jackson Rudd D, Schaeffer A, De Lepeleire I, Friedman EJ, Robberechts M, Zhang S, Liu Y, Kandala B, Keicher C, Daumer M, Hofmann J, Grobler JA, Stoch SA, Iwamoto M, Ankrom W. Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):191-198. doi: 10.1097/QAI.0000000000002834.