Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03615183
Recruitment Status : Recruiting
First Posted : August 3, 2018
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus AIDS Virus Drug: MK-8527 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 11, 2019
Estimated Primary Completion Date : December 13, 2019
Estimated Study Completion Date : December 13, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Panel A
Single oral dose of 10 mg MK-8527 capsule after an 8-hour fast
Drug: MK-8527
Single oral capsule

Experimental: Panel B
Single oral dose of 25 mg MK-8527 capsule after an 8-hour fast
Drug: MK-8527
Single oral capsule

Experimental: Panel C
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
Single oral capsule

Experimental: Panel D
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
Single oral capsule

Experimental: Panel E
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
Single oral capsule




Primary Outcome Measures :
  1. Change From Baseline in Plasma HIV-1 RNA [ Time Frame: Baseline and 168 hours postdose for each panel ]
    Blood samples taken to determine HIV-1 RNA levels at Predose (baseline) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose. The change from Baseline in plasma HIV-1 RNA (log10 copies/mL) in participants administered MK-8527 will be calculated and results will be compared with historical placebo data.

  2. Percentage of Participants Who Report 1 or More Adverse Events (AEs) [ Time Frame: Up to 28 days for each panel ]
    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.

  3. Percentage of Participants Who Were Discontinued From the Study Due to an AE [ Time Frame: Up to 28 days for each panel ]
    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.


Secondary Outcome Measures :
  1. Area Under the Concentration Time-curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527-TP in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Predose and 4, 6, 12, 24, 48, 96, 120, 144, and 168 hours postdose for each panel ]
    Blood samples taken at Predose and 4, 6, 12, 24, 48, 96, 120, 144, and 168 hours postdose of each dosing period to determine the AUC0-168 of MK-8527-TP, the active intercellular component of the study drug in PBMCs.

  2. Area Under the Concentration Time-curve from Hour 0 to last (AUC0-Last) of MK-8527-TP in PBMC [ Time Frame: Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose for each panel ]
    Blood samples taken at Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the AUC0-last of MK-8527-TP, the active intercellular component of the study drug in PBMCs.

  3. Area Under the Concentration Time-curve from Hour 0 to infinity (AUC0-Inf) of MK-8527-TP in PBMC [ Time Frame: Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose for each panel ]
    Blood samples taken at Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the AUC0-inf of MK-8527-TP, the active intercellular component of the study drug in PBMCs.

  4. Maximum Concentration (Cmax) of MK-8527-TP in PBMC [ Time Frame: Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period ]
    Blood samples taken at Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the Cmax of MK-8527-TP, the active intercellular component of the study drug in PBMCs.

  5. Time to Cmax (Tmax) of MK-8527-TP in PBMC [ Time Frame: Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period ]
    Blood samples taken at Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the Tmax of MK-8527-TP, the active intercellular component of the study drug in PBMCs.

  6. Concentration at 168 hours (C168) of MK-8527-TP in PBMC [ Time Frame: 168 hours postdose for each panel ]
    Blood samples taken at Predose and 0. 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 postdose of each dosing period. The concentration of MK-8527-TP in PBMCs at 168 hours postdose was determined.

  7. Apparent terminal t1/2 (t1/2) of MK-8527-TP in PBMC [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each panel ]
    Blood samples taken at Predose and 4, 6, 12, 24, 48, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the t1/2 of MK-8527-TP, the active intercellular component of the study drug in PBMCs.

  8. Area Under the Concentration Time-curve From Hour 0 to 168 Hours (AUC0-168) of MK-8527 in Plasma [ Time Frame: Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose of each panel ]
    Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose of each dosing period to determine the AUC0-168 of MK-8527 in plasma.

  9. Area Under the Concentration Time-curve from Hour 0 to last (AUC0-Last) of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each panel ]
    Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the AUC0-last of MK-8527 in plasma.

  10. Area Under the Concentration Time-curve from Hour 0 to infinity (AUC0-Inf) of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each panel ]
    Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the AUC0-inf of MK-8527 in plasma.

  11. Maximum Concentration (Cmax) of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each panel ]
    Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the Cmax of MK-8527 in plasma.

  12. Time to Cmax (Tmax) of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each panel ]
    Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the Tmax of MK-8527 in plasma.

  13. Concentration at 168 hours (C168) of MK-8527 in Plasma [ Time Frame: 168 hours postdose of each panel ]
    Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period. The concentration of MK-8527 in plasma at 168 hours postdose was determined.

  14. Apparent terminal t1/2 (t1/2) of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each panel ]
    Blood samples taken at Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose of each dosing period to determine the t1/2 of MK-8527 in plasma.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Critieria

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03615183


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Layout table for location information
Romania
Matei Bals Infectious Diseases Institute ( Site 0001) Recruiting
Bucharest, Romania, 021105
Contact: Study Coordinator    +40722218066      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03615183     History of Changes
Other Study ID Numbers: 8527-002
2018-001861-18 ( EudraCT Number )
MK-8527-002 ( Other Identifier: Merck Study Number )
First Posted: August 3, 2018    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Virus Diseases
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases