We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Active, not recruiting
First Posted : July 1, 2019
Last Update Posted : August 25, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE June 27, 2019
First Posted Date  ICMJE July 1, 2019
Last Update Posted Date August 25, 2022
Actual Study Start Date  ICMJE September 19, 2019
Actual Primary Completion Date March 18, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
  • Participants with an adverse event [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 adverse event (AE)
  • Participants who discontinued from study therapy [ Time Frame: Up to week 20 ]
    Percentage of participants who discontinued from study therapy due to an AE
  • Participants with a drug-related AE [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 drug-related AE
  • Participants with a serious adverse event [ Time Frame: Up to Week 68 ]
    Percentage of participants with at least 1 serious AE (SAE)
  • 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
  • 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
  • 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
  • Participants with an AE resulting in death [ Time Frame: Up to Week 68 ]
    Percentage of participants with an AE which results in death
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Participants with an adverse event [ Time Frame: Up to Week 24 ]
    Percentage of participants with at least 1 adverse event (AE)
  • Participants who discontinued from study therapy [ Time Frame: Up to week 20 ]
    Percentage of participants who discontinued from study therapy due to an AE
  • Participants with a drug-related AE [ Time Frame: Up to Week 24 ]
    Percentage of participants with at least 1 drug-related AE
  • Participants with a serious adverse event [ Time Frame: Up to Week 24 ]
    Percentage of participants with at least 1 serious AE (SAE)
  • 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
  • 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
  • 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
  • Participants with an AE resulting in death [ Time Frame: Up to Week 24 ]
    Percentage of participants with an AE which results in death
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Area under the concentration-time curve of plasma MK-8591 [ 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 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 MK-8591
  • Maximum concentration of plasma MK-8591 [ 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 2, 3, 21, 22, 23 and 24: collect at any time during the study visit. ]
    Maximum concentration (Cmax) post-dose of plasma MK-8591
  • Trough concentration of plasma MK-8591 [ 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 2, 3, 21, 22, 23 and 24: collect at any time during the study visit. ]
    Trough concentration (Ctrough) post-dose of plasma MK-8591
  • Apparent terminal half-life of plasma MK-8591 [ 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 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 MK-8591
  • AUC of MK-8591-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, 44, 52, 60, and 68 ]
    AUC from time 0-672 hours post-dose of MK-8591-triphosphate in peripheral blood mononuclear cells (PBMCs)
  • Maximum concentration of MK-8591-triphosphate in PBMCs [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 44, 52, 60, and 68 ]
    Maximum concentration (Cmax) post-dose of MK-8591-triphosphate in PBMCs
  • Trough concentration of MK-8591-triphosphate in PBMCs [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 44, 52, 60, and 68 ]
    Trough concentration (Ctrough) post-dose of MK-8591-triphosphate in PBMCs
  • Apparent terminal half-life of MK-8591-triphosphate in PBMCs [ Time Frame: Day 1, Day 2, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 21, 22, 23, 24, 44, 52, 60, and 68 ]
    Apparent terminal half-life (t1/2) post-dose of MK-8591-triphosphate in PBMCs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Islatravir 60 mg
    60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
    Interventions:
    • Drug: Islatravir
    • Drug: Placebo
  • Experimental: Islatravir 120 mg
    120 mg islatravir administered once monthly, orally in capsule form for 24 weeks
    Intervention: Drug: Islatravir
  • Placebo Comparator: Placebo
    Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
    Intervention: Drug: Placebo
Publications * Devanathan AS, Cottrell ML. Pharmacology of HIV Cure: Site of Action. Clin Pharmacol Ther. 2021 Apr;109(4):841-855. doi: 10.1002/cpt.2187. Epub 2021 Mar 5. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 7, 2022)
242
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2019)
250
Estimated Study Completion Date  ICMJE March 30, 2023
Actual Primary Completion Date March 18, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel,   South Africa,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04003103
Other Study ID Numbers  ICMJE 8591-016
Merck Protocol Number ( Other Identifier: MK-8591-016 )
2019-001704-38 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP