HIV-1
Conditions
Brief summary
This study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral therapy (ART) activity of islatravir (MK-8591) monotherapy in ART-naive, human immunodeficiency virus-1 (HIV-1) infected participants. The primary hypothesis is that at a safe and tolerable dose of islatravir, the true mean difference in the plasma HIV-1 ribonucleic acid (RNA) reduction from baseline between islatravir and placebo is at least 0.5 log (base10) copies/mL.
Interventions
DRUG1 mg islatravir
Single oral dose of 1 mg islatravir administered following ≥8 hour fast
DRUG2 mg islatravir
Single oral dose of 2 mg islatravir administered following ≥8 hour fast
DRUG10 mg islatravir
Single oral dose of 10 mg islatravir administered following ≥8 hour fast
DRUG30 mg islatravir
Single oral dose of 30 mg islatravir administered following ≥8 hour fast
DRUG0.5 mg islatravir
Single oral dose of 0.5 mg islatravir administered following ≥8 hour fast
DRUG0.25 mg islatravir
Single oral dose of 0.25 mg islatravir administered following ≥8 hour fast
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Non-pregnant, non-breast feeding, postmenopausal or surgically sterile female * Female with reproductive potential agrees to use (or have male partner use) two acceptable methods of birth control * Male agrees to use acceptable method of contraception during study and for 90 days after last dose of trial drug * Has stable baseline health, other than HIV infection * Has no significantly abnormal electrocardiogram * Is HIV-1 positive * Have a screening plasma HIV-1 RNA ≥ 10,000 copies/mL within 30 days prior to the treatment phase of this study. For inclusion in Panel Islatravir Extended Observation, participants must also have a screening plasma HIV-1 RNA ≤ 25,000 copies/mL within 30 days prior to the treatment phase. * Is ART naive * Has not received any investigational agent or marketed ART within 30 days of trial drug administration * Is diagnosed with HIV-1 infection \>= 3 months prior to screening * Is willing to receive no other ART during treatment phase of study * Has no evidence of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs)
Exclusion criteria
* Is mentally or legally institutionalized/incapacitated, or has significant emotional problems, or has a history of clinically significant psychiatric disorder of the last 5 years * Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary, major neurological abnormalities or diseases * Has a history of cancer (malignancy) * Has a history of significant multiple and/or severe allergies, or had an anaphylactic reaction to drugs or food * Is positive for hepatitis B surface antigen * Has a history of chronic Hepatitis C * Had major surgery or lost 500 mL of blood with 4 weeks prior to screening visit * Has participated in another investigational trial within 4 weeks prior to dosing visit * Will use any medications, prescribed drugs, or herbal remedies 4 weeks prior to dosing of trial drug, up to the post-trial visit * Consumes excessive amounts of alcohol, caffeinated beverages, or tobacco products * Uses illicit drugs or has a history of drug abuse within the prior 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose | Baseline and 168 hours (7 days) post-dose | Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches. |
| Number of Participants With One or More Adverse Events | Up to 21 days post-dose | An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) | 168 hours after islatravir administration | Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine C168hr. |
| Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample. | Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine TMax. |
| Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample. | Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine apparent terminal t1/2. |
| Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) | 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample. | Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine AUC0-168hr. |
| Maximum Plasma Concentration (Cmax) of Islatravir | Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration | Blood was collected for the determination of Cmax of islatravir in plasma. |
| Time to Maximum Plasma Concentration (Tmax) of Islatravir | Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration | Blood was collected for the determination of Tmax of islatravir in plasma. |
| Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma | Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration | Blood was collected for the determination of apparent terminal t1/2 of islatravir in plasma. |
| Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) | Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration. Value at 168 hours was extrapolated. | Blood was collected for the determination of AUC0-168hr of islatravir in plasma. |
| Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample. | Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine Cmax. |
Participant flow
Pre-assignment details
Additional panels (F: 0.25 mg islatravir; and G: 30 mg islatravir Extended Observation) were initially planned but were not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Panel A: 10 mg Islatravir Participants received a single dose of 10 mg islatravir. | 6 |
| Panel B: 2 mg Islatravir Participants received a single dose of 2 mg islatravir. | 6 |
| Panel C: 30 mg Islatravir Participants received a single dose of 30 mg islatravir. | 6 |
| Panel D: 1 mg Islatravir Participants received a single dose of 1 mg islatravir. | 6 |
| Panel E: 0.5 mg Islatravir Participants received a single dose of 0.5 mg islatravir. | 6 |
| Total | 30 |
Baseline characteristics
| Characteristic | Panel A: 10 mg Islatravir | Panel B: 2 mg Islatravir | Panel C: 30 mg Islatravir | Panel D: 1 mg Islatravir | Panel E: 0.5 mg Islatravir | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 31.5 Years STANDARD_DEVIATION 10 | 42.2 Years STANDARD_DEVIATION 9.8 | 35.5 Years STANDARD_DEVIATION 9.1 | 32.7 Years STANDARD_DEVIATION 12.7 | 35.5 Years STANDARD_DEVIATION 11.3 | 35.5 Years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Plasma HIV-1 Ribonucleic Acid (RNA) | 4.68 log10 copies/mL STANDARD_DEVIATION 0.39 | 4.7 log10 copies/mL STANDARD_DEVIATION 0.25 | 4.17 log10 copies/mL STANDARD_DEVIATION 0.41 | 4.66 log10 copies/mL STANDARD_DEVIATION 0.2 | 4.59 log10 copies/mL STANDARD_DEVIATION 0.5 | 4.56 log10 copies/mL STANDARD_DEVIATION 0.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 29 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 6 | 5 / 6 | 6 / 6 | 5 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose
Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches.
Time frame: Baseline and 168 hours (7 days) post-dose
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had available plasma HIV-1 RNA data at baseline and 168 hours post-dose, and were evaluable for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: 10 mg Islatravir | Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose | -1.67 log10 copies/mL |
| Panel B: 2 mg Islatravir | Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose | -1.35 log10 copies/mL |
| Panel C: 30 mg Islatravir | Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose | -1.60 log10 copies/mL |
| Panel D: 1 mg Islatravir | Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose | -1.30 log10 copies/mL |
| Panel E: 0.5 mg Islatravir | Change From Baseline in Plasma HIV-1 RNA at 168 Hours Post-Dose | -1.20 log10 copies/mL |
Comparison: Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean of pooled historical placebo data was -0.03 log10 copies/mL (95% CI -014, 0.09) change from baseline at 168 hours post dose.
Comparison: Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean of pooled historical placebo data was -0.03 log10 copies/mL (95% CI -014, 0.09) change from baseline at 168 hours post dose.
Comparison: Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean of pooled historical placebo data was -0.03 log10 copies/mL (95% CI -014, 0.09) change from baseline at 168 hours post dose.
Comparison: Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean of pooled historical placebo data was -0.03 log10 copies/mL (95% CI -014, 0.09) change from baseline at 168 hours post dose.
Comparison: Adjusted by Placebo data pooled from historical placebo data from recent monotherapy studies in HIV-1 infected participants (NCT00100048, NCT01466985, NCT01152255, and NCT01353898) and fitted with a longitudinal data analysis (LDA) model containing fixed effects for study and time, and a random effect for participants. LS mean of pooled historical placebo data was -0.03 log10 copies/mL (95% CI -014, 0.09) change from baseline at 168 hours post dose.
Primary
Number of Participants With One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to 21 days post-dose
Population: All participants who received at least one dose of investigational drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: 10 mg Islatravir | Number of Participants With One or More Adverse Events | 5 Participants |
| Panel B: 2 mg Islatravir | Number of Participants With One or More Adverse Events | 5 Participants |
| Panel C: 30 mg Islatravir | Number of Participants With One or More Adverse Events | 6 Participants |
| Panel D: 1 mg Islatravir | Number of Participants With One or More Adverse Events | 5 Participants |
| Panel E: 0.5 mg Islatravir | Number of Participants With One or More Adverse Events | 6 Participants |
Secondary
Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma
Blood was collected for the determination of apparent terminal t1/2 of islatravir in plasma.
Time frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had apparent terminal t1/2 of islatravir in plasma data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma | 59.7 Hours | Geometric Coefficient of Variation 15.4 |
| Panel B: 2 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma | 47.4 Hours | Geometric Coefficient of Variation 74.6 |
| Panel C: 30 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma | 56.8 Hours | Geometric Coefficient of Variation 11.2 |
| Panel D: 1 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma | 10.4 Hours | Geometric Coefficient of Variation 144 |
| Panel E: 0.5 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir in Plasma | 2.31 Hours | Geometric Coefficient of Variation 16.7 |
Secondary
Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine apparent terminal t1/2.
Time frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had apparent terminal t1/2 of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 128 Hours | Geometric Coefficient of Variation 42.2 |
| Panel B: 2 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 120 Hours | Geometric Coefficient of Variation 14.7 |
| Panel C: 30 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 78.5 Hours | Geometric Coefficient of Variation 31.4 |
| Panel D: 1 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 118 Hours | Geometric Coefficient of Variation 16.1 |
| Panel E: 0.5 mg Islatravir | Apparent Terminal Half-Life (t1/2) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 95.3 Hours | Geometric Coefficient of Variation 38.2 |
Secondary
Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr)
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine AUC0-168hr.
Time frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had AUC0-168hr of triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) | 227 hr*pmol/10^6 cells | Geometric Coefficient of Variation 33.3 |
| Panel B: 2 mg Islatravir | Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) | 46.9 hr*pmol/10^6 cells | Geometric Coefficient of Variation 38.1 |
| Panel C: 30 mg Islatravir | Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) | 926 hr*pmol/10^6 cells | Geometric Coefficient of Variation 47.7 |
| Panel D: 1 mg Islatravir | Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) | 35.9 hr*pmol/10^6 cells | Geometric Coefficient of Variation 27.6 |
| Panel E: 0.5 mg Islatravir | Area Under the Concentration-Time Curve of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells From Time 0 to 168 Hours (AUC0-168hr) | 23.1 hr*pmol/10^6 cells | Geometric Coefficient of Variation 83 |
Secondary
Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr)
Blood was collected for the determination of AUC0-168hr of islatravir in plasma.
Time frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration. Value at 168 hours was extrapolated.
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had plasma AUC-168hr of islatravir data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) | 1020 hr*nM | Geometric Coefficient of Variation 16.8 |
| Panel B: 2 mg Islatravir | Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) | 143 hr*nM | Geometric Coefficient of Variation 39.6 |
| Panel C: 30 mg Islatravir | Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) | 3020 hr*nM | Geometric Coefficient of Variation 24.6 |
| Panel D: 1 mg Islatravir | Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) | 88.3 hr*nM | Geometric Coefficient of Variation 33.8 |
| Panel E: 0.5 mg Islatravir | Area Under the Plasma Concentration-Time Curve of Islatravir From Time 0 to 168 Hours (AUC0-168hr) | 38.3 hr*nM | Geometric Coefficient of Variation 25.8 |
Secondary
Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr)
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine C168hr.
Time frame: 168 hours after islatravir administration
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had C168hr of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) | 0.983 pmol/10^6 cells | Geometric Coefficient of Variation 26 |
| Panel B: 2 mg Islatravir | Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) | 0.188 pmol/10^6 cells | Geometric Coefficient of Variation 39.2 |
| Panel C: 30 mg Islatravir | Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) | 4.83 pmol/10^6 cells | Geometric Coefficient of Variation 85.9 |
| Panel D: 1 mg Islatravir | Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) | 0.164 pmol/10^6 cells | Geometric Coefficient of Variation 31.4 |
| Panel E: 0.5 mg Islatravir | Concentration of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells at 168 Hours Post-Dose (C168hr) | 0.116 pmol/10^6 cells | Geometric Coefficient of Variation 85.6 |
Secondary
Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine Cmax.
Time frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had Cmax of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 2.81 pmol/10^6 cells | Geometric Coefficient of Variation 49.9 |
| Panel B: 2 mg Islatravir | Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 0.495 pmol/10^6 cells | Geometric Coefficient of Variation 62.9 |
| Panel C: 30 mg Islatravir | Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 8.9 pmol/10^6 cells | Geometric Coefficient of Variation 60.3 |
| Panel D: 1 mg Islatravir | Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 0.408 pmol/10^6 cells | Geometric Coefficient of Variation 49.3 |
| Panel E: 0.5 mg Islatravir | Maximum Concentration (Cmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 0.263 pmol/10^6 cells | Geometric Coefficient of Variation 54.5 |
Secondary
Maximum Plasma Concentration (Cmax) of Islatravir
Blood was collected for the determination of Cmax of islatravir in plasma.
Time frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had plasma Cmax of islatravir data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: 10 mg Islatravir | Maximum Plasma Concentration (Cmax) of Islatravir | 235 nM | Geometric Coefficient of Variation 32.1 |
| Panel B: 2 mg Islatravir | Maximum Plasma Concentration (Cmax) of Islatravir | 43.8 nM | Geometric Coefficient of Variation 51.2 |
| Panel C: 30 mg Islatravir | Maximum Plasma Concentration (Cmax) of Islatravir | 678 nM | Geometric Coefficient of Variation 29.6 |
| Panel D: 1 mg Islatravir | Maximum Plasma Concentration (Cmax) of Islatravir | 38.8 nM | Geometric Coefficient of Variation 31.3 |
| Panel E: 0.5 mg Islatravir | Maximum Plasma Concentration (Cmax) of Islatravir | 20.3 nM | Geometric Coefficient of Variation 36.4 |
Secondary
Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells
Blood was collected to measure intracellular islatravir triphosphate concentration in peripheral blood mononuclear cells and determine TMax.
Time frame: 4, 12, 24, 96, 120, 144, and 168 hours after islatravir administration. Value at predose was inferred from plasma predose sample.
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had Tmax of islatravir triphosphate in peripheral blood mononuclear cells data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: 10 mg Islatravir | Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 12 Hour |
| Panel B: 2 mg Islatravir | Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 8 Hour |
| Panel C: 30 mg Islatravir | Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 24 Hour |
| Panel D: 1 mg Islatravir | Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 8 Hour |
| Panel E: 0.5 mg Islatravir | Time to Maximum Concentration (Tmax) of Islatravir Triphosphate in Peripheral Blood Mononuclear Cells | 12 Hour |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Islatravir
Blood was collected for the determination of Tmax of islatravir in plasma.
Time frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, and 96 hours after islatravir administration
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with study procedures, had plasma Tmax of islatravir data available, and were evaluable for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: 10 mg Islatravir | Time to Maximum Plasma Concentration (Tmax) of Islatravir | 1 Hour |
| Panel B: 2 mg Islatravir | Time to Maximum Plasma Concentration (Tmax) of Islatravir | 0.5 Hour |
| Panel C: 30 mg Islatravir | Time to Maximum Plasma Concentration (Tmax) of Islatravir | 0.75 Hour |
| Panel D: 1 mg Islatravir | Time to Maximum Plasma Concentration (Tmax) of Islatravir | 0.5 Hour |
| Panel E: 0.5 mg Islatravir | Time to Maximum Plasma Concentration (Tmax) of Islatravir | 0.5 Hour |