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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004017-92 | EudraCT Number | ||
| MK-8583-002 | Other Identifier | Merck Protocol Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A: MK-8583 100mg | Experimental | After fasting, a single oral dose of 100 mg MK-8583 in capsule form. |
|
| B: MK-8583 ≤ 150 mg | Experimental | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments |
|
| C: MK-8583 ≤ 150 mg | Experimental | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form, with the dose based on the results from earlier treatments |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8583 | Drug | A single oral dose of MK-8583 in capsule form |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to Day 29 |
| 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. | Day 1 |
| 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. | Baseline (pre-dose) and 168 hours post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charite Research Organisation GmbH ( Site 0001) | Berlin | 10117 | Germany |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | A: MK-8583 100mg | After fasting, a single oral dose of 100 mg MK-8583 in capsule form. |
| FG001 | B: MK-8583 ≤ 150 mg | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. |
| FG002 | C: MK-8583 ≤ 150 mg | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | A: MK-8583 100mg | After fasting, a single oral dose of 100 mg MK-8583 in capsule form. |
| BG001 | B: MK-8583 ≤ 150 mg | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Count of Participants | Participants | Up to Day 29 |
|
Up to Day 29
All participants who received at least one dose of treatment. Due to an earlier than anticipated achievement of the study objectives, a decision was made not to conduct Panels B and C.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK-8583 100 mg | After fasting, a single oral dose of 100 mg MK-8583 in capsule form. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 9, 2018 | Feb 14, 2020 | Prot_SAP_000.pdf |
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| Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose |
| 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. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose |
| 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. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose |
| 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). | 168 hr postdose |
| 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. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose |
| 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). | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| 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. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
| BG002 | C: MK-8583 ≤ 150 mg | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| A: MK-8583 100mg |
After fasting, a single oral dose of 100 mg MK-8583 in capsule form. |
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Day 1 |
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | log10 copies/mL | Baseline (pre-dose) and 168 hours post-dose. |
|
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*nmol/L | Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours postdose |
|
|
|
| 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. | 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. | Posted | Median | Full Range | hr. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose |
|
|
|
| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 168 hr postdose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 312 and 672 hours postdose |
|
|
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*nmol/L | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
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| 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. | 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. | Posted | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
| 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. | 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. | Posted | Median | Full Range | hr. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
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| 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. | 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. | Posted | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
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| 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. | 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. | Posted | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
| 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. | 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. | Posted | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*nmol/L | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*nmol/L | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
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| 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. | 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. | Posted | Median | Full Range | hr. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours postdose |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 4 |
| 5 |
| EG001 | B: MK-8583 ≤ 150 mg | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | C: MK-8583 ≤ 150 mg | After fasting, a single oral dose of ≤ 150 mg MK-8583 in capsule form. | 0 | 0 | 0 | 0 | 0 | 0 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment | Due to the nature of this Adverse Event and the small sample size for this study, the specific Adverse Event term for this Adverse Event is not disclosed due to patient confidentiality concerns. |
|
| Hepatic enzyme increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.