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Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04003103
Recruitment Status : Completed
First Posted : July 1, 2019
Results First Posted : March 21, 2023
Last Update Posted : April 12, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
This study will evaluate the safety, tolerability and pharmacokinetics (PK) of 6 once-monthly doses of oral islatravir (60 mg and 120 mg) compared with placebo in adults at low risk of HIV-1 infection

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Islatravir Drug: Placebo Phase 2

Detailed Description:
This study is ongoing for collection of safety follow-up of infants born to mothers participating in the study. The present results are based on the Week 68 interim analysis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral MK-8591 Once-Monthly in Participants at Low- Risk for HIV-1 Infection
Actual Study Start Date : September 19, 2019
Actual Primary Completion Date : March 18, 2022
Actual Study Completion Date : November 24, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Islatravir 60 mg
60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
Drug: Islatravir
Islatravir 30 mg capsules taken by mouth.
Other Name: MK-8591

Drug: Placebo
Placebo capsules taken by mouth.

Experimental: Islatravir 120 mg
120 mg islatravir administered once monthly, orally in capsule form for 24 weeks
Drug: Islatravir
Islatravir 30 mg capsules taken by mouth.
Other Name: MK-8591

Placebo Comparator: Placebo
Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
Drug: Placebo
Placebo capsules taken by mouth.




Primary Outcome Measures :
  1. Number of Participants With ≥1 Adverse Event (AE) Through Week 36 [ Time Frame: Up to 36 weeks ]
    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.

  2. Number of Participants Discontinuing From Study Therapy Due to AE [ Time Frame: Up to 20 weeks ]
    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 Therapy Due to ≥1 Drug-related AE [ Time Frame: Up to 20 weeks ]
    A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.

  4. Number of Participants With ≥1 Drug-related AE Through Week 36 [ Time Frame: Up to 36 weeks ]
    A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.

  5. Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36 [ Time Frame: Up to 36 weeks ]
    An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.

  6. Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36 [ Time Frame: Up to 36 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').

  7. Number of Participants With ≥1 Drug-related SAE Through Week 36 [ Time Frame: Up to 36 weeks ]
    An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.

  8. Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36 [ Time Frame: Up to 36 weeks ]
    A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).

  9. Number of Participants With an AE Resulting in Death Through Week 36 [ Time Frame: Up to 36 weeks ]
    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 Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL [ Time Frame: Day 1 and Day 140: predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit. ]
    The AUC0-672 of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

  2. Maximum Plasma Concentration (Cmax) of ISL [ Time Frame: Day 1 and Week 20, collect predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit. ]
    The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

  3. Trough Plasma Concentration (Ctrough) of ISL [ Time Frame: Day 1 and Week 20: predose and 30-min postdose. Day 2: 24 hours post Day 1 dose. Weeks 1, 2, 3, 21, 22, 23 and 24: any time during the study visit. Weeks 4, 8, 12 and 16: predose. ]
    The plasma Ctrough of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

  4. Apparent Plasma Terminal Half-life (t1/2) of ISL [ Time Frame: Day 1 and Week 20, collect predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit. ]
    The plasma t1/2 of ISL after dosing on Day 140 is reported. Only ISL-treated participants are included in the PK analysis.

  5. Number of Participants With ≥1 AE Through Week 24 [ Time Frame: Up to 24 weeks ]
    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.

  6. Number of Participants With ≥1 Drug-related AE Through Week 24 [ Time Frame: Up to 24 weeks ]
    A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.

  7. Number of Participants With ≥1 SAE Through Week 24 [ Time Frame: Up to 24 weeks ]
    An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.

  8. Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24 [ Time Frame: Up to 24 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').

  9. Number of Participants With ≥1 Drug-related SAE Through Week 24 [ Time Frame: Up to 24 weeks ]
    An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.

  10. Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24 [ Time Frame: Up to 24 weeks ]
    A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).

  11. Number of Participants With an AE Resulting in Death Through Week 24 [ Time Frame: Up to 24 weeks ]
    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.



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 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Is in general good health with acceptable laboratory values at screening
  • Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test result before randomization
  • Has low risk of HIV infection, within 12 months prior to screening visit or the rescreening visit (if applicable)
  • Use contraceptives consistent with local regulations
  • Female is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP)
  • A WOCBP is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; or has a negative pregnancy test.

Exclusion Criteria:

  • Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
  • Has an active diagnosis of hepatitis due to any cause
  • Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 30 days prior to Day

    1 through the duration of the study.

  • Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to Day1 through the duration of the study.
  • Has previously been randomized in a study and received islatravir (MK-8591).
  • Female is expecting to conceive or donate eggs at any time during the study
  • Has QTc interval (using Fridericia correction) >450 msec (for males) or >460 msec (for females) or deemed clinically abnormal by the investigator.

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): NCT04003103


Locations
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United States, Florida
Research Centers of America, LLC ( Site 0007)
Hollywood, Florida, United States, 33024
United States, Maryland
Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)
Baltimore, Maryland, United States, 21287
United States, Nebraska
Celerion, Inc. ( Site 0006)
Lincoln, Nebraska, United States, 68502
United States, Pennsylvania
Magee Womens Research Institute ( Site 0001)
Pittsburgh, Pennsylvania, United States, 15213
Israel
Hadassah Ein Karem Jerusalem ( Site 0016)
Jerusalem, Yerushalayim, Israel, 9112001
Rambam Medical Center ( Site 0017)
Haifa, Israel, 3109601
South Africa
JOSHA Research ( Site 0015)
Bloemfontein, Free State, South Africa, 9301
Clinical HIV Research Unit CHRU ( Site 0014)
Johannesburg, Gauteng, South Africa, 2092
Emavundleni Vaccine Centre ( Site 0011)
Cape Town, Western Cape, South Africa, 7750
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:
Study Protocol  [PDF] December 8, 2021
Statistical Analysis Plan  [PDF] December 8, 2021

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04003103    
Other Study ID Numbers: 8591-016
Merck Protocol Number ( Other Identifier: MK-8591-016 )
2019-001704-38 ( EudraCT Number )
First Posted: July 1, 2019    Key Record Dates
Results First Posted: March 21, 2023
Last Update Posted: April 12, 2023
Last Verified: April 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
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Disease Attributes
Pathologic Processes
Islatravir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents