A Study of MK-8527 in Human Immunodeficiency Type 1 Virus (HIV-1) Infected Participants (MK-8527-002)

NCT03615183 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 8527-0022018-001861-18MK-8527-002
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus; AIDS Virus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Plasma HIV-1 RNA

  Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.

  Baseline and 168 hours postdose

• Percentage of Participants Who Report 1 or More Adverse Events (AEs)

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized.

  Up to 28 days

• Percentage of Participants Who Were Discontinued From the Study Due to an AE

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized.

  Up to 28 days

Secondary Outcomes (14)

• Area Under the Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC)

  Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose

• Area Under the Concentration Time Curve From Hour 0 to Last (AUC0-last) of MK-8527-TP in PBMC

  Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

• Area Under the Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-8527-TP in PBMC

  Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

• Maximum Concentration (Cmax) of MK-8527-TP in PBMC

  Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

• Time to Cmax (Tmax) of MK-8527-TP in PBMC

  Predose and 4, 12, 24, 96, 120, 144, 168, 240, 336, 504, 672 hours or 28 days postdose

Study Arms (5)

Panel A: 10 mg MK-8527

EXPERIMENTAL

Single oral dose of 10 mg MK-8527 capsule after an 8-hour fast

Drug: MK-8527

Panel B: 3 mg MK-8527

EXPERIMENTAL

Single oral dose of 3 mg MK-8527 capsule after an 8-hour fast

Drug: MK-8527

Panel C: 1 mg MK-8527

EXPERIMENTAL

Single oral dose of 1 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels.

Drug: MK-8527

Panel D: ≤50 mg MK-8527

EXPERIMENTAL

Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels.

Drug: MK-8527

Panel E: ≤50 mg MK-8527

EXPERIMENTAL

Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels.

Drug: MK-8527

Interventions

MK-8527 DRUG

Single oral capsule

Panel A: 10 mg MK-8527; Panel B: 3 mg MK-8527; Panel C: 1 mg MK-8527; Panel D: ≤50 mg MK-8527; Panel E: ≤50 mg MK-8527

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Matei Bals Infectious Diseases Institute ( Site 0001)

Bucharest, 021105, Romania

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: February 11, 2019
• Primary Completion: September 26, 2019
• Study Completion: September 26, 2019
• Last Updated: September 28, 2020
• Results First Posted: September 28, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

RO (1)