HIV-1 Infection
Conditions
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
This study is ongoing for collection of safety follow-up of infants born to mothers participating in the study. The present results are based on the Week 68 interim analysis.
Interventions
DRUGIslatravir
Islatravir 30 mg capsules taken by mouth.
DRUGPlacebo
Placebo capsules taken by mouth.
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ≥1 Adverse Event (AE) Through Week 36 | Up to 36 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 From Study Therapy Due to 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. |
| Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE | Up to 20 weeks | A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy. |
| Number of Participants With ≥1 Drug-related AE Through Week 36 | Up to 36 weeks | A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention. |
| Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36 | Up to 36 weeks | An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event. |
| Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36 | Up to 36 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death'). |
| Number of Participants With ≥1 Drug-related SAE Through Week 36 | Up to 36 weeks | An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy. |
| Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36 | Up to 36 weeks | A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1). |
| Number of Participants With an AE Resulting in Death Through Week 36 | Up to 36 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 |
|---|---|---|
| Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24 | Up to 24 weeks | A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1). |
| Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL | Day 1 and Day 140: 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. | The AUC0-672 of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis. |
| Number of Participants With an AE Resulting in Death Through Week 24 | Up to 24 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. |
| Maximum Plasma Concentration (Cmax) of ISL | 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. | The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis. |
| Trough Plasma Concentration (Ctrough) of ISL | Day 1 and Week 20: predose and 30-min postdose. Day 2: 24 hours post Day 1 dose. Weeks 1, 2, 3, 21, 22, 23 and 24: any time during the study visit. Weeks 4, 8, 12 and 16: predose. | The plasma Ctrough of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis. |
| Apparent Plasma Terminal Half-life (t1/2) of ISL | 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. | The plasma t1/2 of ISL after dosing on Day 140 is reported. Only ISL-treated participants are included in the PK analysis. |
| Number of Participants With ≥1 AE Through Week 24 | Up to 24 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 With ≥1 Drug-related AE Through Week 24 | Up to 24 weeks | A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention. |
| Number of Participants With ≥1 SAE Through Week 24 | Up to 24 weeks | An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event. |
| Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24 | Up to 24 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death'). |
| Number of Participants With ≥1 Drug-related SAE Through Week 24 | Up to 24 weeks | An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy. |
Countries
Israel, South Africa, United States
Participant flow
Recruitment details
Healthy HIV-uninfected male and female participants were enrolled at 9 study centers in 3 countries.
Participants by arm
| Arm | Count |
|---|---|
| Islatravir 60 mg Participants receive two ISL 30 mg capsules + two ISL placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68. | 97 |
| Islatravir 120 mg Participants receive four ISL 30 mg capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68. | 97 |
| Placebo Participants receive four placebo capsules once monthly from Day 1 to Week 24 plus 12 weeks of follow-up in the Treatment Phase. The Extended Follow-up Phase is from Week 36 to Week 68. | 48 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 3 | 2 |
| Overall Study | Status not recorded | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 1 | 1 |
Baseline characteristics
| Characteristic | Islatravir 60 mg | Islatravir 120 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 33.6 Years STANDARD_DEVIATION 9.9 | 33.2 Years STANDARD_DEVIATION 9.7 | 30.9 Years STANDARD_DEVIATION 7.9 | 32.9 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 9 Participants | 8 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 88 Participants | 40 Participants | 206 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants | 48 Participants | 16 Participants | 101 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 3 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 55 Participants | 44 Participants | 29 Participants | 128 Participants |
| Sex: Female, Male Female | 66 Participants | 64 Participants | 33 Participants | 163 Participants |
| Sex: Female, Male Male | 31 Participants | 33 Participants | 15 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 97 | 0 / 97 | 0 / 48 |
| other Total, other adverse events | 24 / 97 | 23 / 97 | 16 / 48 |
| serious Total, serious adverse events | 1 / 97 | 0 / 97 | 0 / 48 |
Outcome results
Primary
Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.
Time frame: Up to 20 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE | 1 Participants |
| Islatravir 120 mg | Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE | 1 Participants |
| Placebo | Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE | 0 Participants |
Primary
Number of Participants Discontinuing From Study Therapy Due to 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 participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants Discontinuing From Study Therapy Due to AE | 1 Participants |
| Islatravir 120 mg | Number of Participants Discontinuing From Study Therapy Due to AE | 1 Participants |
| Placebo | Number of Participants Discontinuing From Study Therapy Due to AE | 0 Participants |
Primary
Number of Participants With ≥1 Adverse Event (AE) Through Week 36
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 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Adverse Event (AE) Through Week 36 | 66 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Adverse Event (AE) Through Week 36 | 63 Participants |
| Placebo | Number of Participants With ≥1 Adverse Event (AE) Through Week 36 | 36 Participants |
Primary
Number of Participants With ≥1 Drug-related AE Through Week 36
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.
Time frame: Up to 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Drug-related AE Through Week 36 | 9 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Drug-related AE Through Week 36 | 14 Participants |
| Placebo | Number of Participants With ≥1 Drug-related AE Through Week 36 | 12 Participants |
Primary
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36
A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).
Time frame: Up to 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36 | 0 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36 | 0 Participants |
| Placebo | Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36 | 0 Participants |
Primary
Number of Participants With ≥1 Drug-related SAE Through Week 36
An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.
Time frame: Up to 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Drug-related SAE Through Week 36 | 0 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Drug-related SAE Through Week 36 | 0 Participants |
| Placebo | Number of Participants With ≥1 Drug-related SAE Through Week 36 | 0 Participants |
Primary
Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36
An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.
Time frame: Up to 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36 | 1 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36 | 0 Participants |
| Placebo | Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36 | 0 Participants |
Primary
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').
Time frame: Up to 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36 | 5 Participants |
| Islatravir 120 mg | Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36 | 4 Participants |
| Placebo | Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36 | 1 Participants |
Primary
Number of Participants With an AE Resulting in Death Through Week 36
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 36 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With an AE Resulting in Death Through Week 36 | 0 Participants |
| Islatravir 120 mg | Number of Participants With an AE Resulting in Death Through Week 36 | 0 Participants |
| Placebo | Number of Participants With an AE Resulting in Death Through Week 36 | 0 Participants |
Secondary
Apparent Plasma Terminal Half-life (t1/2) of ISL
The plasma t1/2 of ISL after dosing on Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
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.
Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Islatravir 60 mg | Apparent Plasma Terminal Half-life (t1/2) of ISL | Day 1 | NA Hours | — |
| Islatravir 60 mg | Apparent Plasma Terminal Half-life (t1/2) of ISL | Day 140 | 175 Hours | Geometric Coefficient of Variation 16.2 |
| Islatravir 120 mg | Apparent Plasma Terminal Half-life (t1/2) of ISL | Day 1 | NA Hours | — |
| Islatravir 120 mg | Apparent Plasma Terminal Half-life (t1/2) of ISL | Day 140 | 177 Hours | Geometric Coefficient of Variation 19.8 |
Secondary
Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL
The AUC0-672 of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Time frame: Day 1 and Day 140: 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.
Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Islatravir 60 mg | Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL | Day 1 | 7.88 hr*umol/L | Geometric Coefficient of Variation 56.8 |
| Islatravir 60 mg | Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL | Day 140 | 21.2 hr*umol/L | Geometric Coefficient of Variation 140.3 |
| Islatravir 120 mg | Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL | Day 1 | 16.6 hr*umol/L | Geometric Coefficient of Variation 50.5 |
| Islatravir 120 mg | Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL | Day 140 | 37.6 hr*umol/L | Geometric Coefficient of Variation 136.6 |
Secondary
Maximum Plasma Concentration (Cmax) of ISL
The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
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.
Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Islatravir 60 mg | Maximum Plasma Concentration (Cmax) of ISL | Day 1 | 0.387 µmol/L | Geometric Coefficient of Variation 279.9 |
| Islatravir 60 mg | Maximum Plasma Concentration (Cmax) of ISL | Day 140 | 0.376 µmol/L | Geometric Coefficient of Variation 597.7 |
| Islatravir 120 mg | Maximum Plasma Concentration (Cmax) of ISL | Day 1 | 0.954 µmol/L | Geometric Coefficient of Variation 186.2 |
| Islatravir 120 mg | Maximum Plasma Concentration (Cmax) of ISL | Day 140 | 0.792 µmol/L | Geometric Coefficient of Variation 349.6 |
Secondary
Number of Participants With ≥1 AE Through Week 24
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 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 AE Through Week 24 | 58 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 AE Through Week 24 | 60 Participants |
| Placebo | Number of Participants With ≥1 AE Through Week 24 | 32 Participants |
Secondary
Number of Participants With ≥1 Drug-related AE Through Week 24
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.
Time frame: Up to 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Drug-related AE Through Week 24 | 9 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Drug-related AE Through Week 24 | 14 Participants |
| Placebo | Number of Participants With ≥1 Drug-related AE Through Week 24 | 12 Participants |
Secondary
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24
A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).
Time frame: Up to 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24 | 0 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24 | 0 Participants |
| Placebo | Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24 | 0 Participants |
Secondary
Number of Participants With ≥1 Drug-related SAE Through Week 24
An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.
Time frame: Up to 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 Drug-related SAE Through Week 24 | 0 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 Drug-related SAE Through Week 24 | 0 Participants |
| Placebo | Number of Participants With ≥1 Drug-related SAE Through Week 24 | 0 Participants |
Secondary
Number of Participants With ≥1 SAE Through Week 24
An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.
Time frame: Up to 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With ≥1 SAE Through Week 24 | 1 Participants |
| Islatravir 120 mg | Number of Participants With ≥1 SAE Through Week 24 | 0 Participants |
| Placebo | Number of Participants With ≥1 SAE Through Week 24 | 0 Participants |
Secondary
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').
Time frame: Up to 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24 | 3 Participants |
| Islatravir 120 mg | Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24 | 3 Participants |
| Placebo | Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24 | 1 Participants |
Secondary
Number of Participants With an AE Resulting in Death Through Week 24
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 24 weeks
Population: All participants who received ≥1 dose of study therapy are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 60 mg | Number of Participants With an AE Resulting in Death Through Week 24 | 0 Participants |
| Islatravir 120 mg | Number of Participants With an AE Resulting in Death Through Week 24 | 0 Participants |
| Placebo | Number of Participants With an AE Resulting in Death Through Week 24 | 0 Participants |
Secondary
Trough Plasma Concentration (Ctrough) of ISL
The plasma Ctrough of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Time frame: Day 1 and Week 20: predose and 30-min postdose. Day 2: 24 hours post Day 1 dose. Weeks 1, 2, 3, 21, 22, 23 and 24: any time during the study visit. Weeks 4, 8, 12 and 16: predose.
Population: ISL-treated participants with data available who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment, according to the underlying scientific model, are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Islatravir 60 mg | Trough Plasma Concentration (Ctrough) of ISL | Day 1 | 0.000556 µmol/L | Geometric Coefficient of Variation 36.6 |
| Islatravir 60 mg | Trough Plasma Concentration (Ctrough) of ISL | Day 140 | 0.000809 µmol/L | Geometric Coefficient of Variation 37 |
| Islatravir 120 mg | Trough Plasma Concentration (Ctrough) of ISL | Day 1 | 0.00101 µmol/L | Geometric Coefficient of Variation 37 |
| Islatravir 120 mg | Trough Plasma Concentration (Ctrough) of ISL | Day 140 | 0.000124 µmol/L | Geometric Coefficient of Variation 42 |