Study to Evaluate the Safety and Tolerability of a Once Daily Dose of 50 mg E2609 in Healthy Japanese Subjects

An adverse event is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious adverse event is defined as any adverse event occurring at any dose that results in any of the following outcomes: results in death; is life threatening; results in inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life function; results in a congenital anomaly/birth defect; or can be defined as any other important medical event.

Laboratory test values will be assigned a low/normal/high (LNH) classification according to whether the value was below (L), within (N), or above (H) the laboratory parameter's reference range. Clinical significance will be determined by the Investigator.

Vital sign measurements (ie, systolic and diastolic blood pressure [BP] [millimeters of mercury (mmHg)], heart rate [beats per minute], respiratory rate [breaths per minute], body temperature [centigrade]) will be obtained in the supine position by a validated method. Clinical significance will be determined by the Investigator.

Twelve-lead standard ECGs will be recorded in triplicate. ECGs will be recorded after the participant has been in the supine position for at least 10 minutes before and during the reading. In addition, all ECGs will be obtained before blood draws. Clinical significance will be determined by the Investigator.

The suicidality rating scale will rate a participant's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The decision to classify an isolated suicidality rating scale response as an adverse event will be exercised through medical and scientific judgment.

Participants reporting adverse events (AEs) relating to abnormal dreams, nightmares, or sleep terrors will be questioned using the Waketime Questionnaire which is comprised of 5 individual questions. A participant is asked to rate the quality of their sleep as: 1, Very sound or restful; 2, Sound or restful; 3, Average quality; 4, Restless; or 5, Very restless.

Cmax is defined as the maximum observed concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered. Using non-compartmental analysis, plasma concentrations of E2609 and metabolites will be analyzed to determine Cmax. Cmax will be summarized as the mean and standard deviation for all participants.

Cmin is defined as the minimum observed concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered. Using non-compartmental analysis, plasma concentrations of E2609 and metabolites will be analyzed to determine Cmin. Cmin will be summarized as the mean and standard deviation for all participants.

Tmax is defined as the time from dosing to reach the maximum observed concentration a drug achieves in a specified compartment or test area of the body after the drug has been administered. Using non-compartmental analysis, plasma concentrations of E2609 and metabolites will be analyzed to determine Tmax. Tmax will be summarized as the median for all participants.

AUC represents the total drug exposure over a defined period of time. Plasma concentrations of E2609 and its metabolites will be analyzed using a non-compartmental analysis approach to determine individual participant estimates of AUC(0-24h). AUC(0-24h) will be summarized as the mean and standard deviation for all participants and will be expressed in nanograms x hour per milliliter (ng*hr/mL).

Terminal half-life is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity. Plasma concentrations of E2609 and its metabolites will be analyzed using a non-compartmental analysis approach to determine t1/2. t1/2 will be summarized as the mean and standard deviation for all participants and will be expressed in hours.

Css,av is the average steady-state concentration of a drug. Steady state will be achieved when the rate of E2609 administration and the rate of E2609 elimination are equal. Plasma concentrations of E2609 and its metabolites will be analyzed using a non-compartmental analysis approach to determine the Css,av.

Rac is equal to the ratio of the AUC during a dosage interval at steady state to the AUC of a dosage interval after the first dose. Plasma concentrations of E2609 and its metabolites will be analyzed using a non-compartmental analysis approach to determine Rac. Rac will be summarized as the mean and standard deviation for all participants

CLss/F is the rate and extent of absorption and clearance of E2609 from the plasma. Plasma concentrations of E2609 and metabolites will be analyzed using a non-compartmental analysis approach to determine CLss/F.

NAT2 genotyping will be conducted, and the predicted phenotype (eg, slow, intermediate, or rapid acetylators) will be used in the statistical analysis to evaluate the relative impact of NAT2 polymorphisms on plasma concentrations of E2609 and/or its metabolites.