Clinical trial NCT03615183: A Study of MK-8527 in Human Immunodeficiency Type 1 Virus (HIV-1) Infected Participants (MK-8527-002)
Official title: A Single-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8527 Monotherapy in Anti-Retroviral Therapy (ART)-Naïve, HIV-1 Infected Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus
AIDS Virus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-08-03
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the anti-retroviral activity of MK-8527 in HIV-1 infected, ART-naïve participants. The primary hypothesis is that MK-8527 has superior anti-retroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours postdose.

Detailed description: Up to five panels (Panels A-E) of 6 participants each will be enrolled in a sequential manner. In each panel, participants will receive a single dose of MK-8527 up to 50 mg. Historical data from previous single does studies will be used for placebo (control) comparisons.

Eligibility criteria: Inclusion Criteria

* Other than HIV infection, is in good health
* Is documented HIV-1 positive
* Diagnosed with HIV-1 infection ≥ 3 months prior to screening or perform the French 2008 Haute Autorité de Santé (HAS) Algorithm to confirm chronic HIV.
* Is ART-naïve which is defined as having never received any antiretroviral agent or the following: ≤30 consecutive days of an investigational antiretroviral agent, excluding an Nucleoside reverse transcriptase inhibitors (NRTI), or ≤60 consecutive days of combination ART not including an NRTI
* Has not received an investigational agent or marketed ART within 30 days of study drug administration
* Is willing to receive no other ART for the monitoring period of the study
* Has a Body Mass Index (BMI) ≤35 kg/m\^2, inclusive
* If the male participant has a female partner(s) of childbearing potential, he must agree to use a medically acceptable method of contraception during the study and for 120 days after the last dose of study drug. If their partner is pregnant, males must agree to use a condom and no additional method of contraception is required for the pregnant partner
* If the participant is a female with reproductive potential, she must demonstrate a serum β-human chorionic gonadotropin (β-hCG) level consistent with the nongravid state at the prestudy (screening) visit and agree to use (and/or have their partner use) 2 acceptable methods of birth control beginning at the prestudy (screening) visit, throughout the study (including washout intervals between treatment periods/panels) and until 28 days after the last dose of study drug.
* If the participant is a postmenopausal female: she is without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at prestudy (screening)
* If the participant is a surgically sterile female: she is status posthysterectomy, or oophorectomy

Exclusion Criteria

* Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma) may be enrolled in the study at the discretion of the investigator.
* Is mentally or legally incapacitated at the time of the prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder over the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
* History of cancer (malignancy)
* History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
* Positive for hepatitis B surface antigen
* 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 (VL)
* Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks
* Unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the poststudy visit.
* Participated in another investigational study within 4 weeks
* Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day.
* Consumes excessive amounts, defined as greater than 6 servings (1 serving approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
* Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
* Has a positive urine drug screen

Primary outcomes:
measure: Change From Baseline in Plasma HIV-1 RNA
timeFrame: Baseline and 168 hours postdose
measure: Percentage of Participants Who Report 1 or More Adverse Events (AEs)
timeFrame: Up to 28 days
measure: Percentage of Participants Who Were Discontinued From the Study Due to an AE
timeFrame: Up to 28 days
Secondary outcomes:
measure: Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose
measure: Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
measure: Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
measure: Maximum Concentration (Cmax) of MK-8527-TP in PBMC
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
measure: Time to Cmax (Tmax) of MK-8527-TP in PBMC
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
measure: Concentration at 168 Hours (C168) of MK-8527-TP in PBMC
timeFrame: 168 hours postdose for each panel
measure: Apparent Terminal Half Life (t1/2) of MK-8527-TP in PBMC
timeFrame: Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose
measure: Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
measure: Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527 in Plasma
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
measure: Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527 in Plasma
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
measure: Maximum Concentration (Cmax) of MK-8527 in Plasma
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
measure: Time to Cmax (Tmax) of MK-8527 in Plasma
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
measure: Concentration at 168 Hours (C168) of MK-8527 in Plasma
timeFrame: 168 hours postdose
measure: Apparent Terminal Half Life (t1/2) of MK-8527 in Plasma
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose
Other outcomes:
Locations:
city: Bucharest
country: Romania
facility: Matei Bals Infectious Diseases Institute ( Site 0001)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: