Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Verubecestat, SCH 900931
MK-8931 · 3 trials · 3 indications
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.
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.
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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) |
| Part 1, Panel A - Severe Renal Impairment Group | EXPERIMENTAL | - |
| Part 1, Panel B - Healthy Control Group to Match Panel A | EXPERIMENTAL | - |
| Part 2, Panel C - Moderate Renal Impairment Group | EXPERIMENTAL | - |
| Part 2, Panel D - Healthy Control Group to Match Panel C | EXPERIMENTAL | - |
| Part 2, Panel E - Mild Renal Impairment Group | EXPERIMENTAL | - |
| Part 2, Panel F - Healthy Control Group to Match Panel E | EXPERIMENTAL | - |
| Treatment A: MK-8931 12 mg | EXPERIMENTAL | Participants receiving 12 mg MK-8931 for 7 days |
| Treatment B: MK-8931 40 mg | EXPERIMENTAL | Participants receiving MK-8931 40 mg for 7 days |
| Treatment C: Placebo matching MK-8931 12 mg or 40 mg | PLACEBO_COMPARATOR | Participants receiving placebo matching MK-8931 12 mg or 40 mg for 7 days |
| Treatment D: MK-8931 60 mg | EXPERIMENTAL | Participant receiving MK-8931 60 mg for 7 days |
| Treatment E: Placebo matching MK-8931 60 mg | PLACEBO_COMPARATOR | Participants receiving placebo matching MK-8931 60 mg for 7 days |
| Name | Type | Description |
|---|---|---|
| MK-8931 | DRUG | MK-8931 40 mg |
| Placebo | DRUG | Placebo capsules, orally, once per day for 7 days |
Inclusion Criteria: Participants with HI 1. Adult male or female participants, 45-85 years of age, inclusive, at screening. 2. Body Mass Index (BMI) ≥ 19 and ≤ 40 kg/m\^2, at screening. 3. Continuous non-smokers or light smokers (\< 10 cigarettes/day or the equivalent). 4. Baseline health is judged...
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MK-8931 is an investigational small molecule being studied for Alzheimer's Disease and Amnestic Mild Cognitive Impairment. It is in Phase 1 clinical development and is not approved by the FDA. The drug is being developed by Merck & Company, Inc. (MRK).
MK-8931 is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The drug is an investigational small molecule in Phase 1 clinical trials for Alzheimer's Disease and Amnestic Mild Cognitive Impairment.
MK-8931 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. Two Phase 1 trials have been completed, with a total enrollment of 44 participants across studies in Alzheimer's Disease and related conditions.
MK-8931 has completed two Phase 1 trials. NCT01496170 studied safety, tolerability, and pharmacodynamics in 32 participants with Alzheimer's Disease. NCT01537757 examined pharmacokinetics in 12 subjects with renal insufficiency. Both trials are completed.
MK-8931 is also known as verubecestat. It is an investigational small molecule being developed by Merck & Company, Inc. for Alzheimer's Disease and Amnestic Mild Cognitive Impairment. The drug is in Phase 1 clinical development.