HIV, HIV Pre-exposure Prophylaxis
Conditions
Brief summary
This double-blind, placebo-controlled study was designed to assess the safety, tolerability, and pharmacokinetics of oral MK-8527 taken once monthly (QM) in participants at low risk for human immunodeficiency virus Type 1 (HIV-1) infection.
Interventions
DRUGMK-8527
MK-8527 capsule
Placebo capsule matched to MK-8527
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test result before randomization * Has low-risk of HIV infection * Females: is not pregnant or breastfeeding and is either not a participant of childbearing potential (POCBP) OR is a POCBP and uses an acceptable contraception or is abstinent from penile-vaginal intercourse
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, including active hepatitis B (HBV) infection (defined as HBsAg-positive) or hepatitis C virus (HCV) infection (defined as detectable HCV ribonucleic acid \[RNA\]) * Prior use of MK-8527 or islatravir (MK-8591)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ≥1 Adverse Event (AE) | Up to ~28 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. |
| Number of Participants Discontinuing Study Therapy Due to Adverse Event (AE) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Day 1: predose and 0.5, 4, and 24 hours postdose. Week 20: 0.5, 4, and 24 hours postdose | The plasma AUC0-last of MK-8527 is reported. |
| Maximum Plasma Concentration (Cmax) of MK-8527 | Day 1: predose and 0.5, 4, and 24 hours postdose. Week 20: 0.5, 4, and 24 hours postdose | The plasma Cmax of MK-8527 is reported. |
Countries
Israel, South Africa, United States
Participant flow
Recruitment details
Adult participants who were at low risk of human immunodeficiency virus Type 1 (HIV-1) infection were recruited.
Participants by arm
| Arm | Count |
|---|---|
| MK-8527 3 mg QM Participants received oral MK-8527 3 mg QM for 6 months, followed by an 8-week blinded safety follow-up period. | 101 |
| MK-8527 6 mg QM Participants received oral MK-8527 6 mg QM for 6 months, followed by an 8-week blinded safety follow-up period. | 101 |
| MK-8527 12 mg QM Participants received oral MK-8527 12 mg QM for 6 months, followed by an 8-week blinded safety follow-up period. | 99 |
| Placebo to MK-8527 Participants received oral placebo matched to MK-8527 QM for 6 months, followed by an 8-week blinded safety follow-up period. | 49 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 | 0 | 0 |
| Overall Study | Miscellaneous | 2 | 0 | 0 | 1 |
| Overall Study | Randomized by mistake (no study treatment given) | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | MK-8527 3 mg QM | MK-8527 6 mg QM | MK-8527 12 mg QM | Placebo to MK-8527 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.4 Years STANDARD_DEVIATION 10.12 | 30.0 Years STANDARD_DEVIATION 9.8 | 29.6 Years STANDARD_DEVIATION 8.84 | 29.8 Years STANDARD_DEVIATION 8.9 | 30.0 Years STANDARD_DEVIATION 9.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 13 Participants | 14 Participants | 11 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants | 86 Participants | 84 Participants | 38 Participants | 291 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants | 40 Participants | 40 Participants | 21 Participants | 145 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 5 Participants | 2 Participants | 17 Participants |
| Race (NIH/OMB) White | 49 Participants | 54 Participants | 51 Participants | 26 Participants | 180 Participants |
| Sex: Female, Male Female | 58 Participants | 59 Participants | 58 Participants | 29 Participants | 204 Participants |
| Sex: Female, Male Male | 43 Participants | 42 Participants | 41 Participants | 20 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 101 | 1 / 99 | 0 / 49 |
| other Total, other adverse events | 38 / 101 | 43 / 101 | 32 / 99 | 21 / 49 |
| serious Total, serious adverse events | 2 / 101 | 0 / 101 | 1 / 99 | 1 / 49 |
Outcome results
Primary
Number of Participants Discontinuing Study Therapy Due to Adverse Event (AE)
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.
Time frame: Up to ~20 weeks
Population: All randomized participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8527 3 mg QM | Number of Participants Discontinuing Study Therapy Due to Adverse Event (AE) | 0 Participants |
| MK-8527 6 mg QM | Number of Participants Discontinuing Study Therapy Due to Adverse Event (AE) | 2 Participants |
| MK-8527 12 mg QM | Number of Participants Discontinuing Study Therapy Due to Adverse Event (AE) | 1 Participants |
| Placebo to MK-8527 | Number of Participants Discontinuing Study Therapy Due to Adverse Event (AE) | 2 Participants |
Primary
Number of Participants With ≥1 Adverse Event (AE)
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.
Time frame: Up to ~28 weeks
Population: All randomized participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8527 3 mg QM | Number of Participants With ≥1 Adverse Event (AE) | 62 Participants |
| MK-8527 6 mg QM | Number of Participants With ≥1 Adverse Event (AE) | 69 Participants |
| MK-8527 12 mg QM | Number of Participants With ≥1 Adverse Event (AE) | 66 Participants |
| Placebo to MK-8527 | Number of Participants With ≥1 Adverse Event (AE) | 31 Participants |
Secondary
Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527
The plasma AUC0-last of MK-8527 is reported.
Time frame: Day 1: predose and 0.5, 4, and 24 hours postdose. Week 20: 0.5, 4, and 24 hours postdose
Population: Participants treated with active MK-8527 who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8527 3 mg QM | Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Day 1 | 0.132 hr*µmol/L | Geometric Coefficient of Variation 84.8 |
| MK-8527 3 mg QM | Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Week 20 | 0.129 hr*µmol/L | Geometric Coefficient of Variation 81.5 |
| MK-8527 6 mg QM | Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Day 1 | 0.397 hr*µmol/L | Geometric Coefficient of Variation 36.1 |
| MK-8527 6 mg QM | Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Week 20 | 0.404 hr*µmol/L | Geometric Coefficient of Variation 37.3 |
| MK-8527 12 mg QM | Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Day 1 | 0.861 hr*µmol/L | Geometric Coefficient of Variation 34.1 |
| MK-8527 12 mg QM | Area Under the Plasma Concentration-Time Curve From Dosing to Last Measurable Concentration (AUC0-last) of MK-8527 | Week 20 | 0.836 hr*µmol/L | Geometric Coefficient of Variation 55 |
Secondary
Maximum Plasma Concentration (Cmax) of MK-8527
The plasma Cmax of MK-8527 is reported.
Time frame: Day 1: predose and 0.5, 4, and 24 hours postdose. Week 20: 0.5, 4, and 24 hours postdose
Population: Participants treated with active MK-8527 who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8527 3 mg QM | Maximum Plasma Concentration (Cmax) of MK-8527 | Day 1 | 0.0289 µmol/L | Geometric Coefficient of Variation 69 |
| MK-8527 3 mg QM | Maximum Plasma Concentration (Cmax) of MK-8527 | Week 20 | 0.0320 µmol/L | Geometric Coefficient of Variation 67.5 |
| MK-8527 6 mg QM | Maximum Plasma Concentration (Cmax) of MK-8527 | Day 1 | 0.0490 µmol/L | Geometric Coefficient of Variation 75.6 |
| MK-8527 6 mg QM | Maximum Plasma Concentration (Cmax) of MK-8527 | Week 20 | 0.0538 µmol/L | Geometric Coefficient of Variation 73.5 |
| MK-8527 12 mg QM | Maximum Plasma Concentration (Cmax) of MK-8527 | Day 1 | 0.113 µmol/L | Geometric Coefficient of Variation 64.5 |
| MK-8527 12 mg QM | Maximum Plasma Concentration (Cmax) of MK-8527 | Week 20 | 0.108 µmol/L | Geometric Coefficient of Variation 72.5 |