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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 : Recruiting
First Posted : July 1, 2019
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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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

Study Design
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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 : December 15, 2020
Estimated Study Completion Date : October 19, 2021

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: 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 once monthly for 24 weeks
Other Name: MK-8591

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


Outcome Measures
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Primary Outcome Measures :
  1. Participants with an adverse event [ Time Frame: Up to Week 24 ]
    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 24 ]
    Percentage of participants with at least 1 drug-related AE

  4. Participants with a serious adverse event [ Time Frame: Up to Week 24 ]
    Percentage of participants with at least 1 serious AE (SAE)

  5. Participants with a Grade 3 to 5 AE [ Time Frame: Up to Week 24 ]
    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 24 ]
    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 24 ]
    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 24 ]
    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. AUC of islatravir-triphosphate in peripheral blood mononuclear cells [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 25-26, 26-27, 28, 32, 36, 25-26, 26-27, 28, 32, 36, 44, 52, 60, and 68 ]
    AUC from time 0-672 hours post-dose of islatravir-triphosphate in peripheral blood mononuclear cells (PBMCs)

  6. Maximum concentration of islatravir-triphosphate in PBMCs [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 25-26, 26-27, 28, 32, 36, 25-26, 26-27, 28, 32, 36, 44, 52, 60, and 68 ]
    Maximum concentration (Cmax) post-dose of islatravir-triphosphate in PBMCs

  7. Trough concentration of islatravir-triphosphate in PBMCs [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 25-26, 26-27, 28, 32, 36, 44, 52, 60, and 68 ]
    Trough concentration (Ctrough) post-dose of islatravir-triphosphate in PBMCs

  8. Apparent terminal half-life of islatravir-triphosphate in PBMCs [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 25-26, 26-27, 28, 32, 36, 44, 52, 60, and 68 ]
    Apparent terminal half-life (t1/2) post-dose of islatravir-triphosphate in PBMCs


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 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
  • 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.
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): NCT04003103


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

Locations
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United States, Florida
Research Centers of America, LLC ( Site 0007) Recruiting
Hollywood, Florida, United States, 33024
Contact: Study Coordinator    954-990-7649      
United States, Maryland
Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002) Recruiting
Baltimore, Maryland, United States, 21287
Contact: Study Coordinator    443-287-7156      
United States, Nebraska
Celerion, Inc. ( Site 0006) Recruiting
Lincoln, Nebraska, United States, 68502
Contact: Study Coordinator    402-437-6390      
United States, Pennsylvania
Magee Womens Research Institute ( Site 0001) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Study Coordinator    412-383-1313      
Israel
Rambam Medical Center ( Site 0017) Recruiting
Haifa, Heifa, Israel, 3109601
Contact: Study Coordinator    +97247776700      
Hadassah Ein Karem Jerusalem ( Site 0016) Recruiting
Jerusalem, Yerushalayim, Israel, 9112001
Contact: Study Coordinator    +97226779374      
South Africa
JOSHA Research ( Site 0015) Recruiting
Bloemfontein, Free State, South Africa, 9300
Contact: Study Coordinator    +27514128160      
Clinical HIV Research Unit CHRU ( Site 0014) Recruiting
Johannesburg, Gauteng, South Africa, 2092
Contact: Study Coordinator    +27112768800      
Emavundleni Vaccine Centre ( Site 0011) Recruiting
Cape Town, Western Cape, South Africa, 7750
Contact: Study Coordinator    +27216505851      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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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: March 27, 2020
Last Verified: March 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