A Trial of Centanafadine Efficacy, Safety, and Tolerability in Adult Subjects With Binge Eating Disorder

Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities

Laboratory assessments included hematology, serum chemistry, and urinalysis. Abnormality criteria included: In milligrams per deciliter (mg/dL) \[high bilirubin ≥2.0, low/high calcium ≤8.2/ ≥12, high cholesterol fasting ≥240, high glucose, fasting ≥100, high triglycerides, fasting ≥150, high urate ≥8.5 female / ≥10.5 male, high protein urine ≥2 units increase\]; high creatine kinase (units per liter \[U/L\]) \>3xupper limit of normal (ULN); high eosinophils/leukocytes ≥10%, low neutrophils/leukocytes ≤15%; In 10\^3/microliter (µL) \[low or high leukocytes ≤2.8x10\^9/L or ≥16.0x10\^9/L, low neutrophils ≤1.5x10\^9/L\]. The categories with at least one participant with clinically relevant value are reported here.

Time frame: From first dose of study drug up to 1 week post last dose (Up to 9 weeks)

Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities

Vital sign measurements included heart rate in supine and standing positions (low: \<50 beats per minute \[bpm\] and decrease ≥10 bpm; High: \>100 bpm and increase ≥10 bpm), systolic blood pressure (BP) in supine and standing positions (low: \<90 millimeters of mercury \[mmHg\] and decrease ≥20 mmHg; High: ≥140 mmHg and increase ≥20 mmHg), diastolic BP in supine and standing positions (low: \<60 mmHg and decrease ≥10 mmHg; High: ≥90 mmHg and increase ≥10 mmHg), weight in kilograms (kg) (low: ≥7% decrease; High: ≥7% increase), orthostatic hypotension, (≥30mmHg decrease is systolic BP or ≥20 mmHg in diastolic BP after at least 3 minutes of standing compared to the previous supine BP), and orthostatic tachycardia (≥25 bpm increase in heart rate from supine to standing). The categories with at least one participant with clinically relevant value are reported here.

Time frame: From first dose of study drug up to 1 week post last dose (Up to 9 weeks)

Number of Participants With Potentially Clinically Relevant 12-Lead Electrocardiogram (ECG) Abnormalities

12-lead ECG abnormality criteria included Rhythm: Supraventricular premature beat (not present at baseline and present post baseline); and Conduction: Primary (1°) atrioventricular block (PR ≥200 milliseconds \[msec\] and increase of ≥50 msec).

Time frame: From first dose of study drug up to 1 week post last dose (Up to 9 weeks)

Study Medication Withdrawal Questionnaire (SMWQ) Total Mean Score

SMWQ is a questionnaire to assess withdrawal symptoms subsequent to completion of dosing with IMP. The SMWQ is a modification of the Amphetamine Withdrawal Questionnaire, in which in which the terms "amphetamines and methamphetamine" are replaced with the term "the study medication." This change was intended to prevent bias by implying that the trial medication might be an amphetamine or amphetamine-like stimulant when presented with the survey. This questionnaire comprises of 13 items which describe symptoms associated with the cessation of study medication use for which participants indicate severity on a scale with scores ranging from 0 (no withdrawal symptoms) to 4 (most severe withdrawal symptom). The total score is calculated as the sum of all the scores for the 13 items, ranging from 0 to 52. Lower scores indicate less withdrawal symptoms.

Time frame: Week 8

Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score

The HAM-A scale assesses both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). It consists of 14 items to rate the severity of symptoms of anxiety, each scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Total score was calculated as the sum of the 14 individual item scores, ranging from 0 to 56 and categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. A higher score indicates a more severe anxiety.

Time frame: Baseline, Week 8

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

The MADRS is a diagnostic questionnaire used by clinician to assess the participant's severity of depression. The questionnaire includes questions on ten symptoms: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, difficulty concentrating, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each question is scored on a range of 0 to 6 points and the total score was calculated as the sum of the 10 individual item scores, ranging from 0 to 60 categorized as: 0 to 6: normal/symptoms absent, 7 to 19: mild depression, 20 to 34: moderate depression, and 35 to 60: severe depression. Higher scores indicate increased depressive symptoms.

Time frame: Baseline, Week 8

Number of Participants With Suicidality as Measured by Columbia Suicide Severity Rating Scale (C-SSRS) Score

The C-SSRS is a clinician-administered instrument that systematically assess suicidal ideation (SI) and suicidal behavior rating scale. It rates an individual's degree of SI on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). The scale identifies specific behaviors ranging from "preparatory acts or behavior" to "suicide" which may be indicative of an individual's intent to complete suicide. Suicidality was reported in this outcome measure, defined as at least 1 occurrence of suicidal ideation or at least 1 occurrence of suicidal behavior for each assessment period.

Time frame: Week 8