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| ID | Type | Description | Link |
|---|---|---|---|
| Celerion Project Number | Other Identifier | CA13011 | |
| Merck Protocol Number | Other Identifier | MK-8931-016 |
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This study consists of Part I and an optional Part II. The purpose of Part I is to compare the plasma pharmacokinetics of verubecestat (MK-8931) following administration of a single oral dose of 40 mg MK-8931 to participants with moderate hepatic insufficiency (HI) to that of healthy matched controls. An interim safety and pharmacokinetic analysis on the basis of Part I will be performed in order to support the decision to continue with the optional Part II. If a decision to continue with Part II is made, participants with mild HI will be enrolled to receive a single oral dose of 40mg MK-8931. If any healthy participants from Part I do not meet the matching criteria for Part II additional healthy participants will be enrolled.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: MK-8931 40 mg in Moderate HI Participants | Experimental | Single oral dose of MK-8931 40 mg tablet in participants with moderate HI in fasted state (Part I) |
|
| Part I: MK-8931 40 mg in Healthy Participants | Active Comparator | Single oral dose of MK-8931 40 mg tablet in healthy matched participants in fasted state (Part I) |
|
| Part II: MK-8931 40 mg in Mild HI Participants | Experimental | Single oral dose of MK-8931 40 mg tablet in participants with mild HI in fasted state (Part II) |
|
| Part II: MK-8931 40 mg in Healthy Participants | Active Comparator | Single oral dose of MK-8931 40 mg tablet in healthy matched participants in fasted state (Part II) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8931 | Drug | MK-8931 40 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Versus Time Curve of MK-8931 From 0 to Infinity (AUC0-∞) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-∞, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) extrapolated to infinity after a single oral dose of MK-8931 40 mg. Individual AUC0-∞ values were natural log (ln) transformed and evaluated with an analysis of covariance (ANCOVA) model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-∞ in each arm. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
| Maximum Observed Plasma Concentration of MK-8931 (Cmax) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Cmax, defined as the maximum plasma concentration of MK-8931 observed following oral dosing. Individual Cmax values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for Cmax in each arm. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose |
| Area Under the Concentration Versus Time Curve of MK-8931 From 0 to the Time of the Last Quantifiable (Above LLOQ) Sample (AUC0-last) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-last, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) to the time of the last sample with quantifiable MK-8931 (above the lower limit of quantification; LLOQ) after a single oral dose of MK-8931 40 mg. Individual AUC0-last values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-last in each arm. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing an Adverse Event | The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE. |
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Inclusion Criteria: Participants with HI
Adult male or female participants, 45-85 years of age, inclusive, at screening.
Body Mass Index (BMI) ≥ 19 and ≤ 40 kg/m^2, at screening.
Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).
Baseline health is judged to be stable based on medical history (except for the hepatic insufficiency condition).
Participant has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI with features of cirrhosis due to any etiology.
Part 1 only: Participant's score on the Child-Pugh scale must range from 7 to 9 (moderate HI) at screening.
Part 2 only: Participant's score on the Child-Pugh scale must range from 5 to 6 (mild HI) at screening.
Participants must be completely informed of the unknown risks of pregnancy and agree not to become pregnant or father a child during the time they are participating in this study.
For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to dosing and throughout the study or be using an acceptable birth control method.
Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing.
Male participants must agree not to donate sperm from dosing until 90 days after dosing.
Understands the study procedures in informed consent forms (ICFs), be willing and able to comply with the protocol, and provides written informed consent for the trial, including for Future Biomedical Research. Future Biomedical Research participation is voluntary and is not required in order to participate in the trial.
Inclusion Criteria: Healthy Control Participants
Healthy adult male or female participants, 45-85 years of age, inclusive, at screening.
BMI ≥ 19 and ≤ 40 kg/m^2 at screening.
Continuous non-smokers or light smokers (< 10 cigarettes/day or the equivalent).
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator.
Participants must be completely informed of the unknown risks of pregnancy and agree not to become pregnant or father a child during the time they are participating in this study.
For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to dosing and throughout the study or be using an acceptable birth control method.
Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing.
Male participants must agree not to donate sperm from dosing until 90 days after dosing.
Understands the study procedures in ICFs, be willing and able to comply with the protocol, and provides written informed consent for the trial, including for Future Biomedical Research. Future Biomedical Research participation is voluntary and is not required in order to participate in the trial.
Exclusion Criteria: Participants with HI
Exclusion Criteria: Healthy Control Participants
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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Per protocol, this study was divided into Part I and an optional Part II, with Part II initiating only after interim analysis (IA) of Part I. Following Part I IA, the pharmacokinetic (PK) criterion necessary to initiate enrollment for Part II was not met. As a result, the study was completed normally without enrollment into the optional Part II.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part I: MK-8931 40 mg in Moderate HI Participants | Single oral dose of MK-8931 (40 mg tablet) in participants with moderate Hepatic Insufficiency (HI) in fasted state (Part I) |
| FG001 | Part I: MK-8931 40 mg in Healthy Participants | Single oral dose of MK-8931 (40 mg tablet) in healthy matched participants in fasted state (Part I) |
| FG002 | Part II: MK-8931 40 mg in Mild HI Participants | Single oral dose of MK-8931 (40 mg tablet) in participants with mild HI in fasted state (Part II) |
| FG003 | Part II: MK-8931 40 mg in Healthy Participants | Single oral dose of MK-8931 (40 mg tablet) in healthy matched participants in fasted state (Part II) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part I: MK-8931 40 mg in Moderate HI Participants | Single oral dose of MK-8931 (40 mg tablet) in participants with moderate HI in fasted state (Part I) |
| BG001 | Part I: MK-8931 40 mg in Healthy Participants |
| 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 | Area Under the Concentration Versus Time Curve of MK-8931 From 0 to Infinity (AUC0-∞) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-∞, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) extrapolated to infinity after a single oral dose of MK-8931 40 mg. Individual AUC0-∞ values were natural log (ln) transformed and evaluated with an analysis of covariance (ANCOVA) model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-∞ in each arm. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of AUC0-∞. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | micromolar(µM)*hour(hr) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
Up to 14 days following MK-8931 40 mg administration.
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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 | Part I: MK-8931 40 mg in Moderate HI Participants | Single oral dose of MK-8931 (40 mg tablet) in participants with moderate HI in fasted state (Part I) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | 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 | Jan 5, 2017 | Feb 7, 2018 | Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000613570 | verubecestat |
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|
| Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
| Area Under the Concentration Versus Time Curve of MK-8931 From 0 to 24 Hours (AUC0-24hr) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-24hr, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) until 24 hours after single oral dosing of MK-8931 40 mg. Individual AUC0-24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-24hr in each arm. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after MK-8931 40 mg dose |
| Plasma Concentration of MK-8931 at 24 Hours (C24hr) | Blood samples were collected 24 hours following oral dosing of MK-8931 and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified to determine C24hr, defined as the plasma concentration of MK-8931 at 24 hours after single oral dosing of MK-8931 40 mg. Individual C24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for C24hr in each arm. | 24 hours after MK-8931 40 mg dose |
| Apparent Clearance of MK-8931 After Extravascular Administration (CL/F) | Geometric mean apparent clearance of MK-8931 after extravascular administration (CL/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine CL/F, defined as the rate of MK-8931 elimination normalized to the bioavailability of MK-8931 in the plasma following oral MK-8931 administration. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
| Time to Maximum Observed MK-8931 Plasma Drug Concentration (Tmax) | Median time to maximum observed MK-8931 plasma drug concentration (Tmax) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Tmax, defined as the amount of time required following MK-8931 administration for the plasma concentration of MK-8931 to reach maximum observed concentration. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose |
| Apparent Terminal Half-Life of MK-8931 (t1/2) | Geometric mean apparent terminal half-life (t1/2) of MK-8931 was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine t1/2, defined as the time required for the plasma MK-8931 concentration to decrease to 50% of maximum. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
| Apparent Volume of Distribution of MK-8931 During the Terminal Phase After Extravascular Administration (Vz/F) | Geometric mean apparent volume of distribution of MK-8931 during the terminal phase after extravascular administration (Vz/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Vz/F, defined as the total amount of MK-8931 administered normalized to the bioavailability of MK-8931 in the plasma during the terminal phase following oral MK-8931 administration. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
| Up to 14 days following MK-8931 40 mg administration. |
| Number of Participants Discontinuing Study Due to an Adverse Event | The number of participants discontinuing study due to an AE was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE. | Up to 14 days following MK-8931 40 mg administration. |
Single oral dose of MK-8931 (40 mg tablet) in healthy matched participants in fasted state (Part I)
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Full Range | kg/m^2 |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Part I: MK-8931 40 mg in Moderate HI Participants | Single oral dose of MK-8931 (40 mg tablet) in participants with moderate HI in fasted state (Part I) |
| OG001 | Part I: MK-8931 40 mg in Healthy Participants | Single oral dose of MK-8931 (40 mg tablet) in healthy matched participants in fasted state (Part I) |
|
|
|
| Primary | Maximum Observed Plasma Concentration of MK-8931 (Cmax) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Cmax, defined as the maximum plasma concentration of MK-8931 observed following oral dosing. Individual Cmax values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for Cmax in each arm. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of Cmax. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | nanomolar (nM) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose |
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|
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| Primary | Area Under the Concentration Versus Time Curve of MK-8931 From 0 to the Time of the Last Quantifiable (Above LLOQ) Sample (AUC0-last) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-last, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) to the time of the last sample with quantifiable MK-8931 (above the lower limit of quantification; LLOQ) after a single oral dose of MK-8931 40 mg. Individual AUC0-last values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-last in each arm. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of AUC0-last. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | µM*hr | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
|
|
|
|
| Primary | Area Under the Concentration Versus Time Curve of MK-8931 From 0 to 24 Hours (AUC0-24hr) | Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine AUC0-24hr, defined as the area under the MK-8931 concentration versus time curve from 0 (predose) until 24 hours after single oral dosing of MK-8931 40 mg. Individual AUC0-24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for AUC0-24hr in each arm. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of AUC0-24hr. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | µM*hr | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours after MK-8931 40 mg dose |
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| Primary | Plasma Concentration of MK-8931 at 24 Hours (C24hr) | Blood samples were collected 24 hours following oral dosing of MK-8931 and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified to determine C24hr, defined as the plasma concentration of MK-8931 at 24 hours after single oral dosing of MK-8931 40 mg. Individual C24hr values were ln-transformed and evaluated with an ANCOVA model containing a categorical factor for participant group (Moderate HI, Healthy Matched Control) and continuous covariates for age and BMI. This ANCOVA model was used to compute a geometric least-squares mean and 95% confidence interval for C24hr in each arm. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of C24hr. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | nM | 24 hours after MK-8931 40 mg dose |
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|
|
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| Primary | Apparent Clearance of MK-8931 After Extravascular Administration (CL/F) | Geometric mean apparent clearance of MK-8931 after extravascular administration (CL/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine CL/F, defined as the rate of MK-8931 elimination normalized to the bioavailability of MK-8931 in the plasma following oral MK-8931 administration. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of CL/F. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters/hr | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
|
|
|
| Primary | Time to Maximum Observed MK-8931 Plasma Drug Concentration (Tmax) | Median time to maximum observed MK-8931 plasma drug concentration (Tmax) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Tmax, defined as the amount of time required following MK-8931 administration for the plasma concentration of MK-8931 to reach maximum observed concentration. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of Tmax. | Posted | Median | Full Range | hr | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after MK-8931 40 mg dose |
|
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| Primary | Apparent Terminal Half-Life of MK-8931 (t1/2) | Geometric mean apparent terminal half-life (t1/2) of MK-8931 was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine t1/2, defined as the time required for the plasma MK-8931 concentration to decrease to 50% of maximum. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of t1/2. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
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|
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| Primary | Apparent Volume of Distribution of MK-8931 During the Terminal Phase After Extravascular Administration (Vz/F) | Geometric mean apparent volume of distribution of MK-8931 during the terminal phase after extravascular administration (Vz/F) was assessed. Blood samples were collected at each pre-specified time point and plasma was isolated for analysis. Plasma MK-8931 concentration was then quantified at each time point to determine Vz/F, defined as the total amount of MK-8931 administered normalized to the bioavailability of MK-8931 in the plasma during the terminal phase following oral MK-8931 administration. | All participants who received the single dose of MK-8931 40 mg, complied with trial protocol, and had blood samples available for the evaluation of Vz/F. One participant with moderate HI discontinued study prior to collection of samples at 72, 96, and 120 hours post-dose and was excluded from analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after MK-8931 40 mg dose |
|
|
|
| Secondary | Number of Participants Experiencing an Adverse Event | The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE. | All participants as treated, consisting of all participants receiving the single dose of MK-8931 40 mg. | Posted | Count of Participants | Participants | Up to 14 days following MK-8931 40 mg administration. |
|
|
|
| Secondary | Number of Participants Discontinuing Study Due to an Adverse Event | The number of participants discontinuing study due to an AE was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE. | All participants as treated, consisting of all participants receiving the single dose of MK-8931 40 mg. | Posted | Count of Participants | Participants | Up to 14 days following MK-8931 40 mg administration. |
|
|
|
| 0 |
| 8 |
| 1 |
| 8 |
| 0 |
| 8 |
| EG001 | Part I: MK-8931 40 mg in Healthy Participants | Single oral dose of MK-8931 (40 mg tablet) in healthy matched participants in fasted state (Part I) | 0 | 8 | 0 | 8 | 0 | 8 |
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.
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |