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Trial record 1 of 1 for:    NCT05494736
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MK-8527 Single-Dose Trial in HIV-1 Infected Participants (MK-8527-004)

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ClinicalTrials.gov Identifier: NCT05494736
Recruitment Status : Recruiting
First Posted : August 10, 2022
Last Update Posted : May 15, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief Summary:
This is a single-dose clinical study to evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-8527 in antiretroviral therapy (ART)-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. The primary hypothesis is that, at a dose that is safe and generally well tolerated, MK-8527 will have antiretroviral activity as measured by a reduction from baseline in plasma HIV-1 ribonucleic acid (RNA) of ≥1.0 log10 copies/mL.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-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 : November 17, 2022
Estimated Primary Completion Date : October 23, 2023
Estimated Study Completion Date : October 23, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: Panel A: MK-8527 1.0 mg
Participants receive a single oral dose of MK-8527 1.0 mg.
 Drug: MK-8527
MK-8527 capsule taken by mouth.
Experimental: Panel B: MK-8527 ≤10.0 mg
Participants receive a single oral dose of MK-8527 ≤10.0 mg.
 Drug: MK-8527
MK-8527 capsule taken by mouth.
Experimental: Panel C: MK-8527 ≤10.0 mg
Participants receive a single oral dose of MK-8527 ≤10.0 mg.
 Drug: MK-8527
MK-8527 capsule taken by mouth.


Outcome Measures
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Primary Outcome Measures :
  1. Change from baseline in plasma HIV-1 ribonucleic acid (RNA) [ Time Frame: Baseline and 168 hours postdose on Day 1 ]
    The change from baseline in HIV-1 RNA will be determined.

  2. Number of participants experiencing ≥1 adverse event (AE) [ Time Frame: Up to 28 days ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  3. Number of participants discontinuing from study due to an AE [ Time Frame: Up to 28 days ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.


Secondary Outcome Measures :
  1. Area Under the Concentration-Time Curve from Predose to 168 hours postdose (AUC0-168) of MK-8527 Triphosphate (MK-8527-TP) in Peripheral Blood Mononuclear Cells (PBMCs) [ Time Frame: Predose and 4, 12, 24, 96, 120, 144, and 168 hours postdose ]
    Intracellular MK-8527-TP AUC0-168 will be determined in PBMCs.

  2. Area Under the Concentration-Time Curve from Predose to Last Measurable Concentration (AUC0-last) of MK-8527-TP in PBMCs [ Time Frame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose ]
    Intracellular MK-8527-TP AUC0-last will be determined in PBMCs.

  3. Area Under the Concentration-Time Curve from Predose to Infinity (AUC0-inf) of MK-8527-TP in PBMCs [ Time Frame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose ]
    Intracellular MK-8527-TP AUC0-inf will be determined in PBMCs.

  4. Time to Maximum Concentration (Tmax) of MK-8527-TP in PBMCs [ Time Frame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose ]
    Intracellular MK-8527-TP Tmax will be determined in PBMCs.

  5. Maximum Concentration (Cmax) of MK-8527-TP in PBMCs [ Time Frame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose ]
    Intracellular MK-8527-TP Cmax will be determined in PBMCs.

  6. Concentration at 168 Hours Postdose (C168) of MK-8527-TP in PBMCs [ Time Frame: 168 hours postdose ]
    C168 of MK-8527-TP will be determined in PBMCs.

  7. Apparent terminal half-life (t½) of MK-8527-TP in PBMCs [ Time Frame: Predose and 4, 12, 24, 96, 120, 144, 168, 192, 240, 336, 504, and 672 hours postdose ]
    The apparent t½ of MK-8527-TP will be determined in PBMCs.

  8. AUC0-last of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose ]
    The AUC0-last of MK-8527 will be determined in plasma.

  9. AUC0-inf of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose ]
    The AUC0-inf of MK-8527 will be determined in plasma.

  10. Tmax of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose ]
    The Tmax of MK-8527 will be determined in plasma.

  11. Cmax of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose ]
    The Cmax of MK-8527 will be determined in plasma.

  12. Clast of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose ]
    The Clast of MK-8527 will be determined in plasma.

  13. Apparent t½ of MK-8527 in Plasma [ Time Frame: Predose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose ]
    The apparent t½ of MK-8527 will be determined in plasma.

  14. Correlation Between Intracellular C168 of MK-8527-TP in PBMCs and Change from Baseline in Plasma HIV-1 RNA [ Time Frame: Predose and 168 hours postdose ]
    The correlation between between the C168 of MK-8527-TP in PBMCs and the change from baseline in plasma HIV-1 RNA levels 168 hours after dosing will calculated.


Eligibility Criteria
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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.


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

Inclusion Criteria:

  • Is in good health other than HIV-1 infection
  • Is documented HIV-1 positive
  • Is ART-naïve, which is defined as not having received any marketed antiretroviral agent for treatment of HIV-1 infection (prior use of an ART for PrEP or investigational therapy is permitted if the last dose was ≥30 days prior to study drug administration)
  • Is willing to receive no other ART for the monitoring period of this study
  • If male, agrees to the following during the intervention period and for at least 8 weeks after the last dose of study intervention: abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent; or uses contraception unless confirmed to be azoospermic
  • A female participant is eligible to participate if not pregnant or breastfeeding, and at least one of the following applies: is not a woman of childbearing potential (WOCBP); or is a WOCBP and uses a highly effective contraceptive, has a negative pregnancy test within 24 hours of study intervention administration, abstains from breastfeeding for at least 56 days after study intervention, and has medical/menstrual/recent sexual activity reviewed by the investigator to decrease the risk of an early undetected pregnancy

Exclusion Criteria:

  • Has a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
  • Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years
  • Has a history of cancer (malignancy) other than adequately treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other malignancy that has been successfully treated and unlikely to recur for the duration of the study in the opinion of the investigator
  • Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food
  • Is positive for hepatitis B surface antigen
  • Has a history of chronic hepatitis C unless there has been documented cure
  • Has had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit
  • Is 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 intervention, throughout the study, until the poststudy visit
  • Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit
  • Is an excessive smoker (ie, more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day
  • Consumes greater than 3 servings of alcoholic beverages (1 serving is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day. Participants who consume 4 servings of alcoholic beverages per day may be enrolled at the discretion of the investigator
  • Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
  • Has a positive urine drug screen (except for cannabis or benzodiazepines, for which there is a current prescription from a licensed medical provider) at screening and/or predose; rechecks are allowed
Contacts and Locations
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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): NCT05494736


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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South Africa
Josha Research ( Site 0003) Recruiting
Bloemfontein, Free State, South Africa, 9301
Contact: Study Coordinator    +27825724468      
Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0002) Recruiting
Johannesburg, Gauteng, South Africa, 2092
Contact: Study Coordinator    +27834158967      
Desmond Tutu Health Foundation ( Site 0001) Recruiting
Cape Town, Western Cape, South Africa, 7925
Contact: Study Coordinator    27216506726      
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05494736    
Other Study ID Numbers: 8527-004
MK-8527-004 ( Other Identifier: Merck )
First Posted: August 10, 2022    Key Record Dates
Last Update Posted: May 15, 2023
Last Verified: May 2023
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

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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:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
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