HIV-1 Infection
Conditions
Brief summary
This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-retroviral therapy (ART) activity of the tenofovir prodrug, MK-8583 monotherapy in ART-naïve, HIV-1 infected participants. The primary hypothesis is that at a dose that is sufficiently safe and generally well tolerated, MK-8583 has superior anti-retroviral activity compared to historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours post-dose.
Interventions
DRUGMK-8583
A single oral dose of MK-8583 in capsule form
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male with female partner(s) of child-bearing potential use required methods of birth control. * Female of reproductive potential must demonstrate a nongravid state at the pretrial (screening) visit and agree to use acceptable methods of birth control beginning at the pretrial (screening) visit, throughout the trial and until 30 days following cessation of treatment. * Postmenopausal female, defined as without menses for at least 1 year and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening). * Surgically sterile female's status is post hysterectomy or oophorectomy. * Is documented HIV-1 positive * Is diagnosed with HIV-1 infection ≥ 3 months prior to screening. * Is ART-naïve, defined as having never received any anti-retroviral agent; or ≤ 30 consecutive days of an investigational anti-retroviral agent, excluding a nucleoside reverse transcriptase inhibitor (NRTI), or ≤ 60 consecutive days of combination ART not including a NRTI.
Exclusion criteria
* Is mentally or legally institutionalized/incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder over the last 5 years. * Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases. * Has a history of cancer (malignancy). * Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food. * Is positive for Hepatitis B surface antigen. * Has a history of chronic Hepatitis C unless there has been documented cure. * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit. * Has participated in another investigational trial within 4 weeks or 5 half-lives, whichever is greater, prior to the pre-trial (screening) visit. * Uses or anticipates using any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of trial drug, throughout the trial, until the post-trial visit. * Consumes greater than 3 glasses of alcoholic beverages, wine or distilled spirits per day. * Consumes excessive amounts of caffeinated beverages per day. * Is an excessive smoker (i.e., more than 10 cigarettes/day) and is unwilling to restrict smoking to ≤10 cigarettes per day. * Has a positive urine drug screen (except for cannabis) at screening and/or pre-dose. * Has received any investigational agent or any anti-retroviral agent within 60 days of study drug administration; or intends to receive any ART during this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Adverse Event (AE) | Up to Day 29 | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Number of Participants Who Discontinued Study Due to an AE | Day 1 | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose. | Baseline (pre-dose) and 168 hours post-dose. | Plasma HIV-1 RNA was measured at baseline and 168 hours after dosing. Change from baseline for MK-8583 at 168 hours post-baseline was estimated from longitudinal data analysis (LDA) model containing fixed effects for time (predose, 168 hours postdose) and a random effect for participant. The change from baseline in plasma HIV-1 RNA in participants administered MK-8583 was compared with historical placebo data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration at 168 Hours Postdose (C168hr) of TFV-DP | 168 hr postdose | Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The concentration at 168 hours postdose (C168hr) of TFV-DP is presented. It is hypothesized that the true geometric mean (GM) of TFV-DP in PBMC is ≥ 0.1 μM (100 nmol/L). |
| Apparent Terminal Half-life (t1/2) of TFV-DP | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose | Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of intracellular TFV-DP is presented. |
| Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583 | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma MK-8583 is presented. The last quantified concentration value occurred at 2 hours (n=4) and 4 hours (n=1). |
| Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583 | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. |
| Tmax of Plasma MK-8583. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma MK-8583 is presented. |
| Cmax of MK-8583 | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma MK-8583 is presented. |
| t1/2 of MK-8583 | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. |
| Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP) | Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose | Values of TFV-DP in peripheral blood mononuclear cells (PBMCs) were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-168 hours post-dose (AUC0-168hr) for intracellular TFV-DP is presented. |
| Apparent Volume of Distribution (Vz/F) of MK-8583 | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. |
| AUC0-last of Tenofovir (TFV) | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma TFV is presented. |
| AUC0-inf of TFV | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-infinity (AUC0-inf) of plasma TFV is presented. |
| Tmax of TFV | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma TFV is presented. |
| Cmax of TFV | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma TFV is presented. |
| t1/2 of TFV | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of plasma TFV is presented. |
| Apparent Total Clearance (CL/F) of MK-8583 | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose | Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent total clearance (CL/F) of plasma MK-8583 is presented. |
| Time to Achieve Maximum Concentration (Tmax) of TFV-DP | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose | Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of intracellular TFV-DP is presented. |
| Maximum Concentration (Cmax) of TFV-DP | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose | Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of intracellular TFV-DP is presented. |
Countries
Germany
Participant flow
Recruitment details
Participants with human immunodeficiency virus-1 (HIV-1) infection who were naïve to anti-retroviral therapy (ART) were enrolled. Only participants from Panel A were recruited. Due to an earlier than anticipated achievement of the study objectives, a decision was made not to conduct Panels B and C.
Participants by arm
| Arm | Count |
|---|---|
| A: MK-8583 100mg After fasting, a single oral dose of 100 mg MK-8583 in capsule form. | 5 |
| B: MK-8583 ≤ 150 mg After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. | 0 |
| C: MK-8583 ≤ 150 mg After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. | 0 |
| Total | 5 |
Baseline characteristics
| Characteristic | Total | A: MK-8583 100mg | C: MK-8583 ≤ 150 mg | B: MK-8583 ≤ 150 mg |
|---|---|---|---|---|
| Age, Continuous | 30.2 Years STANDARD_DEVIATION 10.9 | 30.2 Years STANDARD_DEVIATION 10.9 | — | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 4 / 5 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 5 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose.
Plasma HIV-1 RNA was measured at baseline and 168 hours after dosing. Change from baseline for MK-8583 at 168 hours post-baseline was estimated from longitudinal data analysis (LDA) model containing fixed effects for time (predose, 168 hours postdose) and a random effect for participant. The change from baseline in plasma HIV-1 RNA in participants administered MK-8583 was compared with historical placebo data.
Time frame: Baseline (pre-dose) and 168 hours post-dose.
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| A: MK-8583 100mg | Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at 168 Hours Post-dose. | -0.63 log10 copies/mL |
Primary
Number of Participants Who Discontinued Study Due to an AE
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Day 1
Population: All participants who received at least one dose of treatment. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: MK-8583 100mg | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
Primary
Number of Participants With at Least One Adverse Event (AE)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to Day 29
Population: All participants who received at least one dose of treatment. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: MK-8583 100mg | Number of Participants With at Least One Adverse Event (AE) | 4 Participants |
Secondary
Apparent Terminal Half-life (t1/2) of TFV-DP
Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of intracellular TFV-DP is presented.
Time frame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment. One participant who had insufficient data on terminal phase was not included in the analysis. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Apparent Terminal Half-life (t1/2) of TFV-DP | 241 hr. | Geometric Coefficient of Variation 23.7 |
Secondary
Apparent Total Clearance (CL/F) of MK-8583
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent total clearance (CL/F) of plasma MK-8583 is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Due to insufficient plasma concentration data at the terminal phase, CL/F of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
Secondary
Apparent Volume of Distribution (Vz/F) of MK-8583
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Due to insufficient plasma concentration data at the terminal phase, Vz/F of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
Secondary
Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP)
Values of TFV-DP in peripheral blood mononuclear cells (PBMCs) were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-168 hours post-dose (AUC0-168hr) for intracellular TFV-DP is presented.
Time frame: Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Area Under the Concentration Time Curve From Time 0-168 Hours Postdose (AUC0-168hr) of Tenofovir Diphosphate (TFV-DP) | 324000 hr*nmol/L | Geometric Coefficient of Variation 179 |
Secondary
Area Under the Concentration Time Curve From Time 0-infinity (AUC0-inf) of MK-8583
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Due to insufficient plasma concentration data at the terminal phase, AUC0-inf of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
Secondary
Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma MK-8583 is presented. The last quantified concentration value occurred at 2 hours (n=4) and 4 hours (n=1).
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Area Under the Concentration Time Curve From Time 0-last Measurement (AUC0-last) of MK-8583 | 220 hr*nmol/L | Geometric Coefficient of Variation 415 |
Secondary
AUC0-inf of TFV
Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-infinity (AUC0-inf) of plasma TFV is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | AUC0-inf of TFV | 1550 hr*nmol/L | Geometric Coefficient of Variation 108 |
Secondary
AUC0-last of Tenofovir (TFV)
Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The area under the concentration time curve from time 0-last measurement (AUC0-last) of plasma TFV is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | AUC0-last of Tenofovir (TFV) | 1090 hr*nmol/L | Geometric Coefficient of Variation 187 |
Secondary
Cmax of MK-8583
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma MK-8583 is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Cmax of MK-8583 | 258 nmol/L | Geometric Coefficient of Variation 440 |
Secondary
Cmax of TFV
Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of plasma TFV is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Cmax of TFV | 64.3 nmol/L | Geometric Coefficient of Variation 137 |
Secondary
Concentration at 168 Hours Postdose (C168hr) of TFV-DP
Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The concentration at 168 hours postdose (C168hr) of TFV-DP is presented. It is hypothesized that the true geometric mean (GM) of TFV-DP in PBMC is ≥ 0.1 μM (100 nmol/L).
Time frame: 168 hr postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment. The PBMC sample from one participant was processed incorrectly, so was not included in the analysis. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Concentration at 168 Hours Postdose (C168hr) of TFV-DP | 940 nmol/L | Geometric Coefficient of Variation 414 |
Secondary
Maximum Concentration (Cmax) of TFV-DP
Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The maximum concentration (Cmax) of intracellular TFV-DP is presented.
Time frame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | Maximum Concentration (Cmax) of TFV-DP | 4660 nmol/L | Geometric Coefficient of Variation 182 |
Secondary
t1/2 of MK-8583
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Due to insufficient plasma concentration data at the terminal phase, t1/2 of plasma MK-8583 was not able to be calculated for any participants. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
Secondary
t1/2 of TFV
Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The apparent terminal half-life (t1/2) of plasma TFV is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A: MK-8583 100mg | t1/2 of TFV | 31.5 hr. | Geometric Coefficient of Variation 13.2 |
Secondary
Time to Achieve Maximum Concentration (Tmax) of TFV-DP
Values of TFV-DP in PBMCs were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of intracellular TFV-DP is presented.
Time frame: Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: MK-8583 100mg | Time to Achieve Maximum Concentration (Tmax) of TFV-DP | 12 hr. |
Secondary
Tmax of Plasma MK-8583.
Values of plasma MK-8583 were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma MK-8583 is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: MK-8583 100mg | Tmax of Plasma MK-8583. | 1 hr. |
Secondary
Tmax of TFV
Values of plasma TFV were natural-log transformed and analyzed based on a linear model containing a fixed effect for the MK-8583 100-mg dose. The time to achieve maximum concentration (Tmax) of plasma TFV is presented.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants from Panels B and C were not analyzed because they were not enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: MK-8583 100mg | Tmax of TFV | 2 hr. |