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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)

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ClinicalTrials.gov Identifier: NCT04003103
Recruitment Status : Active, not recruiting
First Posted : July 1, 2019
Last Update Posted : December 10, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 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
Estimated Primary Completion Date : March 15, 2022
Estimated Study Completion Date : March 15, 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 administered orally in capsule form swallowed whole once monthly for 24 weeks
Other Name: MK-8591

Drug: Placebo
Placebo for islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks

Experimental: Islatravir 120 mg
120 mg islatravir administered once monthly, orally in capsule form for 24 weeks
Drug: Islatravir
Islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks
Other Name: MK-8591

Placebo Comparator: Placebo
Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
Drug: Placebo
Placebo for islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks




Primary Outcome Measures :
  1. Participants with an adverse event [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 adverse event (AE)

  2. Participants who discontinued from study therapy [ Time Frame: Up to week 20 ]
    Percentage of participants who discontinued from study therapy due to an AE

  3. Participants with a drug-related AE [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 drug-related AE

  4. Participants with a serious adverse event [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 serious AE (SAE)

  5. Participants with a Grade 3 to 5 AE [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 Grade 3 (severe AE) to 5 (death) AE

  6. Participants with a serious and drug-related AE [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 AE which is both serious and drug-related

  7. Participants with a Grade 3 to 5 and drug-related AE [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 AE which is both Grade 3 (severe AE) to 5 (death) AE and drug-related

  8. Participants with an AE resulting in death [ Time Frame: Up to Week 68 ]
    Percentage of participants with an AE which results in death


Secondary Outcome Measures :
  1. Area under the concentration-time curve of plasma islatravir [ 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. ]
    Area under the concentration-time curve (AUC) from time 0 to 672 hours post-dose of plasma islatravir

  2. Maximum concentration of plasma islatravir [ 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. ]
    Maximum concentration (Cmax) post-dose of plasma islatravir

  3. Trough concentration of plasma islatravir [ 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. ]
    Trough concentration (Ctrough) post-dose of plasma islatravir

  4. Apparent terminal half-life of plasma islatravir [ 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. ]
    Apparent terminal half-life (t1/2) post-dose of plasma islatravir

  5. Participants with an AE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 AE up to week 24

  6. Participants with a drug-related AE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 drug-related AE up to week 24

  7. Participants with a SAE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 SAE up to week 24

  8. Participants with Grade 3 to 5 AE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 Grade 3 to 5 AE up to week 24

  9. Participants with a serious and drug-related AE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 serious and drug-related AE up to week 24

  10. Participants with Grade 3 to 5 and drug-related AE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 Grade 3 to 5 and drug-related AE up to week 24

  11. Participants with an AE resulting in death up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 AE resulting in death up to week 24



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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 Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04003103    
Other Study ID Numbers: 8591-016
Merck Protocol Number ( Other Identifier: MK-8591-016 )
First Posted: July 1, 2019    Key Record Dates
Last Update Posted: December 10, 2020
Last Verified: December 2020
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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Infection
Communicable Diseases
4'-ethynyl-2-fluoro-2'-deoxyadenosine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents