Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
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 developed for Alzheimer's disease and amnestic mild cognitive impairment, a condition often preceding Alzheimer's. It has been studied in patients with these conditions, as well as in healthy volunteers with renal or hepatic insufficiency to assess how the body processes the drug.
MK-8931 is being developed by Merck & Company, Inc., a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol MRK. Merck has conducted clinical trials to evaluate the safety, tolerability, and pharmacodynamics of MK-8931 in participants with Alzheimer's disease.
MK-8931 is in Phase 1 clinical development. All three clinical trials listed for MK-8931 are Phase 1 studies that have been completed. The drug is investigational and has not been approved by regulatory authorities, as it remains in early-stage clinical testing.
MK-8931 has been studied in three completed Phase 1 trials: NCT01496170, a safety and pharmacodynamics study in 32 participants with Alzheimer's disease; NCT01537757, a pharmacokinetics study in 12 subjects with renal insufficiency; and NCT02910739, a study in 16 participants with hepatic insufficiency.
MK-8931 is also known as verubecestat. This alternative name is used in some clinical and scientific contexts. The drug has been investigated under both names in research related to Alzheimer's disease and amnestic mild cognitive impairment.
MK-8931 targets the beta-secretase enzyme, also known as BACE1, which plays a role in the production of amyloid-beta plaques in the brain. By inhibiting this enzyme, the drug aims to reduce the formation of these plaques, which are associated with Alzheimer's disease pathology.