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)
Study Details
Study Description
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 |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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 Names:
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 Names:
|
| 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
|
Outcome Measures
Primary Outcome Measures
- Participants with an adverse event [Up to Week 68]
Percentage of participants with at least 1 adverse event (AE)
- Participants who discontinued from study therapy [Up to week 20]
Percentage of participants who discontinued from study therapy due to an AE
- Participants with a drug-related AE [Up to Week 68]
Percentage of participants with at least 1 drug-related AE
- Participants with a serious adverse event [Up to Week 68]
Percentage of participants with at least 1 serious AE (SAE)
- Participants with a Grade 3 to 5 AE [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 [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 [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 [Up to Week 68]
Percentage of participants with an AE which results in death
Secondary Outcome Measures
- Area under the concentration-time curve of plasma islatravir [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Up to week 24]
Percentage of participants with at least 1 AE resulting in death up to week 24
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Centers of America, LLC ( Site 0007) | Hollywood | Florida | United States | 33024 |
| 2 | Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002) | Baltimore | Maryland | United States | 21287 |
| 3 | Celerion, Inc. ( Site 0006) | Lincoln | Nebraska | United States | 68502 |
| 4 | Magee Womens Research Institute ( Site 0001) | Pittsburgh | Pennsylvania | United States | 15213 |
| 5 | Hadassah Ein Karem Jerusalem ( Site 0016) | Jerusalem | Yerushalayim | Israel | 9112001 |
| 6 | Rambam Medical Center ( Site 0017) | Haifa | Israel | 3109601 | |
| 7 | JOSHA Research ( Site 0015) | Bloemfontein | Free State | South Africa | 9301 |
| 8 | Clinical HIV Research Unit CHRU ( Site 0014) | Johannesburg | Gauteng | South Africa | 2092 |
| 9 | Emavundleni Vaccine Centre ( Site 0011) | Cape Town | Western Cape | South Africa | 7750 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8591-016
- Merck Protocol Number
- 2019-001704-38