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

The CGI-S is a standardized, clinician-administered global rating scale that measures disease severity on scale with a score range of 0 to 7 where, 0 = not assessed; 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. A higher score on the CGI-S represents a higher severity of disease. LS mean was determined by MMRM method with change from baseline value as dependent variable and included treatment, trial center, visit week, treatment-by-week interaction as fixed effects and baseline-by-week interaction as covariates.

An AE is defined as any untoward medical occurrence in a clinical trial participant administered an IMP and which does not necessarily have a causal relationship with this treatment. AESIs were newly acquired skin eruptions that were non-traumatic which included eruptions such as skin rashes, skin irritations, skin reactions, or acneiform lesions. AEs related to abuse included: Feeling abnormal (floaty feeling in the head), euphoric mood (feeling high). MHIs included: IMP accounting errors, not involving suspected abuse nor diversion by participant; Non-compliance with trial procedures, not involving suspected abuse nor diversion by participant; and other cases involving neither suspected abuse nor diversion of trial IMP by participant.

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.

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.

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).

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.

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.

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.

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.