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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000998-37 | EudraCT Number | ||
| MK-8504-002 | 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 monotherapy with MK-8504 (a tenofovir pro-drug), in ART-naïve Human Immunodeficiency Virus (HIV)-1 infected participants. The primary hypothesis is that MK-8504, at a dose that is sufficiently safe and well tolerated, has superior antiretroviral activity compared to placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) at 168 hours post-dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-8504 100 mg (Panel A) | Experimental | Participants receive a single oral dose of MK-8504 100 mg. |
|
| MK-8504 240 mg (Panel B) | Experimental | Participants receive a single oral dose of MK-8504 240 mg. |
|
| MK-8504 ≤240 mg (Panel C) | Experimental | Participants receive a single oral dose of MK-8504 ≤240 mg. |
|
| MK-8504 ≤240 mg (Panel D) | Experimental | Participants receive a single oral dose of MK-8504 ≤240 mg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8504 | Drug | After at least an 8-hour fast, a single oral dose of MK-8504 will be administered in capsule form. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) at 168 Hours Post-Dose | Plasma samples were collected from participants after a single dose of MK-8504 to assess viral load. The log10 plasma HIV-RNA (copies/mL) measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. Change from baseline to 168 hours post-dose was determined for each treatment group. Results are expressed as change in HIV RNA log10 (copies/mL). | Baseline, 168 hours post-dose |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants experiencing at least one AE was reported for each arm. | From Day 1 through Post-Trial Visit (up to 25 days) |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants that discontinued study treatment due to an AE was reported for each arm. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Last Measurable Concentration (AUC0-last) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-last of plasma MK-8504. AUC0-last was defined as the area under the concentration time curve of plasma MK-8504 from time 0 to last measurement, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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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 0002) | Berlin | Germany | ||||
| St Stephen's Clinical Research ( Site 0001) |
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Twelve participants infected with Human Immunodeficiency Virus 1 (HIV-1) were enrolled into Panels A and B. Due to an earlier than anticipated achievement of the study primary study objectives, Panels C and D were not conducted and no participants were enrolled in these panels.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-8504 100 mg (Panel A) | Participants receive a single oral dose of MK-8504 100 mg. |
| FG001 | MK-8504 240 mg (Panel B) | Participants receive a single oral dose of MK-8504 240 mg. |
| FG002 | MK-8504 ≤240 mg (Panel C) | Participants were to receive a single oral dose of MK-8504 ≤240 mg. This panel did not enroll any participants. |
| FG003 | MK-8504 ≤240 mg (Panel D) | Participants were to receive a single oral dose of MK-8504 ≤240 mg. This panel did not enroll any participants. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-8504 100 mg (Panel A) | Participants receive a single oral dose of MK-8504 100 mg. |
| BG001 | MK-8504 240 mg (Panel B) | Participants receive a single oral dose of MK-8504 240 mg. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) at 168 Hours Post-Dose | Plasma samples were collected from participants after a single dose of MK-8504 to assess viral load. The log10 plasma HIV-RNA (copies/mL) measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. Change from baseline to 168 hours post-dose was determined for each treatment group. Results are expressed as change in HIV RNA log10 (copies/mL). | All randomized participants | Posted | Least Squares Mean | 95% Confidence Interval | log10 (copies/mL) | Baseline, 168 hours post-dose |
|
From Day 1 through Post-Trial Visit (up to 25 days)
All participants that received at least one dose of treatment.
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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-8504 100 mg (Panel A) | Participants receive a single oral dose of MK-8504 100 mg. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.0 | 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 | Jul 14, 2017 | May 3, 2019 | Prot_SAP_000.pdf |
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| Day 1 |
| Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Infinity (AUC0-inf) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-inf of plasma MK-8504. AUC0-inf was defined as the area under the concentration time curve of plasma MK-8504 from time 0 to infinite time, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to 168 Hours (AUC0-168hr) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-168hr of plasma MK-8504. Because plasma MK-8504 was expected to rapidly disappear from plasma based on prior experience with healthy participants, sampling was done until 72 hrs and AUC0-168 hr was computed from these data assuming 1) a mono-exponential concentration decline after 72hrs; 2) accurate estimation of the elimination rate based on available data; and 3) no involvement of other processes besides elimination after 72 hrs. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Time to Maximum Concentration of MK-8504 in Plasma (Tmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Tmax of plasma MK-8504. Tmax was defined as the time at which maximum concentration of MK-8504 in plasma was observed, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Maximum Concentration of MK-8504 in Plasma (Cmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Cmax of plasma MK-8504. Cmax was defined as the maximum concentration of MK-8504 in plasma observed, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Apparent Terminal Half Life of MK-8504 in Plasma (t½) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine t½ of plasma MK-8504. t½ was defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Apparent Total Clearance of MK-8504 in Plasma (CL/F) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine CL/F of plasma MK-8504. CL/F was defined as the apparent total clearance of the drug from plasma after oral administration, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8504 in Plasma | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Vz/F of plasma MK-8504. Vz/F was defined as the apparent volume of distribution of the drug in plasma during the terminal phase after non-intravenous administration, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to 168 Hours (Intracellular AUC0-168hr) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular AUC0-168hr of TFP-DP in PBMCs. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular AUC0-168hr was defined as the area under the concentration time curve of TFV-DP in PBMCs from time 0 to 168 hours, following a single dose of MK-8504. | Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours post-dose |
| Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to Infinity (Intracellular AUC0-inf) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular AUC0-inf of TFV-DP in PBMCs. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular AUC0-inf was defined as the area under the concentration time curve of TFV-DP in PBMCs from time 0 to infinite time, following a single dose of MK-8504. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
| Intracellular Time to Maximum Concentration (Intracellular Tmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular Tmax of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular Tmax was defined as the time at which maximum intracellular concentration of TFV-DP in PBMCs was observed, following a single dose of MK-8504. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
| Intracellular Maximum Concentration (Intracellular Cmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular Cmax of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular Cmax was defined as the maximum intracellular concentration of TFV-DP in PBMCs observed, following a single dose of MK-8504. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
| Intracellular Apparent Terminal Half Life (Intracellular t½) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular t½ of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular t½ was defined as the time required to divide the intracellular concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504. | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
| Intracellular Concentration of Tenofovir-Diphosphate (TFV-DP) at 168 Hours (Intracellular C168hr) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state, processed for PBMC samples, and used to determine the intracellular C168hr of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular C168hr was defined as the intracellular concentration of TFV-DP in PBMCs at 168 hours, following a single dose of MK-8504. | 168 hours post-dose |
| Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Last Measurable Concentration (AUC0-last) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-last of plasma tenofovir. AUC0-last was defined as the area under the concentration time curve of plasma tenofovir from time 0 to last measurement, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Infinity (AUC0-inf) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-inf of plasma tenofovir. AUC0-inf was defined as the area under the concentration time curve of plasma tenofovir from time 0 to infinite time, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to 168 Hours (AUC0-168hr) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-168hr of plasma tenofovir. Because plasma tenofovir was expected to rapidly disappear from plasma based on prior experience with healthy participants, sampling was done until 72 hrs and AUC0-168 hr was computed from these data assuming 1) a mono-exponential concentration decline after 72hrs; 2) accurate estimation of the elimination rate based on available data; and 3) no involvement of other processes besides elimination after 72 hrs. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Time to Maximum Concentration of Tenofovir in Plasma (Tmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Tmax of plasma tenofovir. Tmax was defined as the time at which maximum concentration of tenofovir in plasma was observed, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Maximum Concentration of Tenofovir in Plasma (Cmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Cmax of plasma tenofovir. Cmax was defined as the maximum concentration of tenofovir in plasma observed, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| Apparent Terminal Half Life of Tenofovir in Plasma (t½) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine t½ of plasma tenofovir. t½ was defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504. | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
| London |
| United Kingdom |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Baseline Plasma HIV-1 Ribonucleic Acid (RNA) | Mean | Standard Deviation | Log10 copies/mL |
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Participants receive a single oral dose of MK-8504 240 mg. |
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| Primary | Number of Participants Who Experienced At Least One Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants experiencing at least one AE was reported for each arm. | All participants that received at least one dose of treatment. | Posted | Count of Participants | Participants | From Day 1 through Post-Trial Visit (up to 25 days) |
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| Primary | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants that discontinued study treatment due to an AE was reported for each arm. | All participants that received at least one dose of treatment. | Posted | Count of Participants | Participants | Day 1 |
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| Secondary | Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Last Measurable Concentration (AUC0-last) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-last of plasma MK-8504. AUC0-last was defined as the area under the concentration time curve of plasma MK-8504 from time 0 to last measurement, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma pharmacokinetic (PK) data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to Infinity (AUC0-inf) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-inf of plasma MK-8504. AUC0-inf was defined as the area under the concentration time curve of plasma MK-8504 from time 0 to infinite time, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Area Under the Concentration-Time Curve of MK-8504 in Plasma From Time 0 to 168 Hours (AUC0-168hr) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-168hr of plasma MK-8504. Because plasma MK-8504 was expected to rapidly disappear from plasma based on prior experience with healthy participants, sampling was done until 72 hrs and AUC0-168 hr was computed from these data assuming 1) a mono-exponential concentration decline after 72hrs; 2) accurate estimation of the elimination rate based on available data; and 3) no involvement of other processes besides elimination after 72 hrs. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Time to Maximum Concentration of MK-8504 in Plasma (Tmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Tmax of plasma MK-8504. Tmax was defined as the time at which maximum concentration of MK-8504 in plasma was observed, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Full Range | Hour (hr) | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Maximum Concentration of MK-8504 in Plasma (Cmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Cmax of plasma MK-8504. Cmax was defined as the maximum concentration of MK-8504 in plasma observed, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Apparent Terminal Half Life of MK-8504 in Plasma (t½) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine t½ of plasma MK-8504. t½ was defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | 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 post-dose |
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| Secondary | Apparent Total Clearance of MK-8504 in Plasma (CL/F) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine CL/F of plasma MK-8504. CL/F was defined as the apparent total clearance of the drug from plasma after oral administration, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters (L)/hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8504 in Plasma | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Vz/F of plasma MK-8504. Vz/F was defined as the apparent volume of distribution of the drug in plasma during the terminal phase after non-intravenous administration, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters (L) | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to 168 Hours (Intracellular AUC0-168hr) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular AUC0-168hr of TFP-DP in PBMCs. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular AUC0-168hr was defined as the area under the concentration time curve of TFV-DP in PBMCs from time 0 to 168 hours, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 4, 12, 24, 48, 72, 96, and 168 hours post-dose |
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| Secondary | Intracellular Area Under the Concentration-Time Curve of Tenofovir-Diphosphate (TFV-DP) From Time 0 to Infinity (Intracellular AUC0-inf) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular AUC0-inf of TFV-DP in PBMCs. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular AUC0-inf was defined as the area under the concentration time curve of TFV-DP in PBMCs from time 0 to infinite time, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
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| Secondary | Intracellular Time to Maximum Concentration (Intracellular Tmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular Tmax of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular Tmax was defined as the time at which maximum intracellular concentration of TFV-DP in PBMCs was observed, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data. | Posted | Geometric Mean | Full Range | hours (hr) | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
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| Secondary | Intracellular Maximum Concentration (Intracellular Cmax) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular Cmax of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular Cmax was defined as the maximum intracellular concentration of TFV-DP in PBMCs observed, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
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| Secondary | Intracellular Apparent Terminal Half Life (Intracellular t½) of Tenofovir-Diphosphate (TFV-DP) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state pre- and post-dose, processed for PBMC samples, and used to determine the intracellular t½ of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular t½ was defined as the time required to divide the intracellular concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour (hr) | Pre-dose, 4, 12, 24, 48, 72, 96, 168, 240, 384, and 600 hours post-dose |
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| Secondary | Intracellular Concentration of Tenofovir-Diphosphate (TFV-DP) at 168 Hours (Intracellular C168hr) In Peripheral Blood Mononuclear Cells (PBMCs) | Blood samples were collected in a fasted state, processed for PBMC samples, and used to determine the intracellular C168hr of TFV-DP. TFV-DP is formed via metabolism of MK-8504 in plasma, PBMC and in other tissues. Intracellular C168hr was defined as the intracellular concentration of TFV-DP in PBMCs at 168 hours, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available PBMC PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | 168 hours post-dose |
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| Secondary | Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Last Measurable Concentration (AUC0-last) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-last of plasma tenofovir. AUC0-last was defined as the area under the concentration time curve of plasma tenofovir from time 0 to last measurement, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma pharmacokinetic (PK) data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to Infinity (AUC0-inf) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-inf of plasma tenofovir. AUC0-inf was defined as the area under the concentration time curve of plasma tenofovir from time 0 to infinite time, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Area Under the Concentration-Time Curve of Tenofovir in Plasma From Time 0 to 168 Hours (AUC0-168hr) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine AUC0-168hr of plasma tenofovir. Because plasma tenofovir was expected to rapidly disappear from plasma based on prior experience with healthy participants, sampling was done until 72 hrs and AUC0-168 hr was computed from these data assuming 1) a mono-exponential concentration decline after 72hrs; 2) accurate estimation of the elimination rate based on available data; and 3) no involvement of other processes besides elimination after 72 hrs. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM·hr | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Time to Maximum Concentration of Tenofovir in Plasma (Tmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Tmax of plasma tenofovir. Tmax was defined as the time at which maximum concentration of tenofovir in plasma was observed, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Full Range | Hour (hr) | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Maximum Concentration of Tenofovir in Plasma (Cmax) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine Cmax of plasma tenofovir. Cmax was defined as the maximum concentration of tenofovir in plasma observed, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, and 72 hours post-dose |
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| Secondary | Apparent Terminal Half Life of Tenofovir in Plasma (t½) | Plasma samples were collected in a fasted state pre- and post-dose and used to determine t½ of plasma tenofovir. t½ was defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-8504. | The analysis population consisted of all participants who received at least 1 dose of study treatment, were compliant with the study procedure, and had available plasma PK data. | 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 post-dose |
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| 0 |
| 6 |
| 0 |
| 6 |
| 5 |
| 6 |
| EG001 | MK-8504 240 mg (Panel B) | Participants receive a single oral dose of MK-8504 240 mg. | 0 | 6 | 0 | 6 | 6 | 6 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Rectal tenesmus | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Catheter site bruise | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Tooth abscess | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Tooth infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Abnormal dreams | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
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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. Sponsor review can be expedited to meet publication timelines.
| PBMC TFV-DP C168hr values pooled, natural log transformed and analyzed based on a linear model containing a fixed effect for dose level. The posterior probability that the true GM of PBMC TFV-DP C168hr level was ≥0.1 μM was calculated for the dose level using flat priors under a normal likelihood assumption. An 80% posterior probability for a dose level that also exhibits acceptable safety and tolerability would satisfy the secondary PK hypothesis. | Posterior Probability (percentage) | 99 | Posterior Probability (percentage) of true geometric mean (GM) C168hr TFV-DP level in PBMCs ≥0.1 μM | Other |