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

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets After Oral Administration in Adult Subjects With Binge Eating Disorder

The primary objective of this study is to assess the efficacy of 2 doses of centanafadine sustained-release (SR) (200 milligrams [mg] and 400 mg total daily dose [TDD]) compared with placebo in adults with moderate to severe binge eating disorder (BED).

Study Overview

• Status: Completed
• Conditions: Binge-Eating Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Centanafadine

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • NoesisPharma, LLC
  • California
    • Beverly Hills, California, United States, 90210
      • Southern California Research LLC
    • Encino, California, United States, 91316
      • Pharmacology Research Institute - San Fernando Valley
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research, LLC
    • Upland, California, United States, 91786
      • Pacific Clinical Research Management Group LLC
  • Colorado
    • Denver, Colorado, United States, 80209
      • Mountain View Clinical Research, LLC
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions - Jacksonville
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta, Pc
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
    • Prairie Village, Kansas, United States, 66208
      • Collective Medical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
  • Missouri
    • Weldon Spring, Missouri, United States, 63304
      • St. Charles Psychiatric Associates & Midwest Research Group
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices and Research - Portsmouth
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
  • New York
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine
    • New York, New York, United States, 10128
      • Medical Research Network, LLC
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Mason, Ohio, United States, 45040
      • Craig and Frances Linder Center of Hope
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78737
      • Psychiatry + Psychotherapy Partners Austin
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult participants 18 to 65 years of age (inclusive) at the time of informed consent.
• A primary diagnosis of BED, or is diagnosed at screening, according to Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) criteria and confirmed by the Structured Clinical Interview for DSM-5 (SCID).
• BED with a history of at least 2 binge eating days per week for 6 months prior to screening.
• A rating of 4 or higher on the Clinical Global Impression - Severity (CGI-S) at screening and baseline.
• Body mass index (BMI) of 18 to 45 kg/m^2, inclusive.

Exclusion Criteria:

• Lifetime history of bulimia nervosa or anorexia nervosa.
• Participation in a formal weight loss program within 3 months of screening or planning to start a weight loss program during the trial.
• History of bariatric surgery.
• Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 18.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Centanafadine 400 mg; Participants will receive centanafadine 200 mg SR tablets, orally, twice daily (BID) at a TDD of 400 mg for 8 weeks.	Drug: Centanafadine; Sustained-release oral tablets
Experimental: Centanafadine 200 mg; Participants will receive centanafadine 100 mg SR tablets, orally, BID at a TDD of 200 mg along with centanafadine matching placebo tablets, orally, BID for 8 weeks.	Drug: Placebo; Oral tablets; Drug: Centanafadine; Sustained-release oral tablets
Placebo Comparator: Placebo; Participants will receive centanafadine matching placebo tablets, orally, BID for 8 weeks.	Drug: Placebo; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Number of Binge Eating Days Per Week	Binge eating day was defined as a day with at least one binge eating episode. Least squares (LS) mean was determined by Mixed-effect Model Repeated Measures (MMRM) method with change from baseline in binge eating days per week at scheduled visit as dependent variable and included fixed effect terms for treatment, trial center, visit week, and an interaction term of treatment by visit week.	Baseline, Weeks 7 to 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score	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.	Baseline, Week 8
Number of Participants With Adverse Events (AEs), Adverse Events of Special Interest (AESIs) Related to Rash, AEs Related to Abuse, and AEs Involving Medication Handling Irregularities (MHIs)	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.	From first dose of study drug up to 1 week post last dose (Up to 9 weeks)
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.	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.	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).	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.	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.	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.	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.	Week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score	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.	Baseline, Weeks 1, 2, 3, 4, and 6
Mean Clinical Global Impression - Change (CGI-C) Score	The CGI-C is a single-item, 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to their baseline state at the beginning of treatment, rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. A higher score on the CGI-C represents a greater disease progression.	Week 8
Change From Baseline in Yale-Brown Obsessive-Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) Score	The Y-BOCS-BE is a clinician-rated scale that assesses obsession with binge eating thoughts and compulsiveness of binge eating behaviors. The Y-BOCS-BE is a 10-item scale, divided into 2 subscales with 5 items each: obsessions and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and total scores range from 0 to 40. A score of 0 to 7 is considered sub-clinical; 8 to 15 as mild; 16 to 23 as moderate; 24 to 31 as severe; and 32 to 40 as extreme obsession and compulsiveness of binge eating. 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.	Baseline, Week 8
Percentage of Participants With Four-Week Cessation From Binging	Percentages are rounded off to the nearest single decimal point.	Week 8
Change From Baseline in Number of Binge Episodes Per Week	All binge eating episodes were recorded daily by the participant in a binge eating diary. At each visit, the investigator reviewed the completed diary and assessed the number of binges for each day. Number of binge episodes per week are reported. 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.	Baseline, Weeks 7 to 8
Change From Baseline in Patient Global Impression - Severity (PGI-S) Score	The PGI-S is a single-item self-report of the participant's severity of symptoms. Severity is rated on a 7-point scale: 1 = no symptoms; 2 = minimal; 3 = mild; 4 = moderate; 5 = marked; 6 = severe; 7 = very severe. A higher score indicates more severe symptoms. 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.	Baseline, Week 8
Mean Patient Global Impression - Change (PGI-C) Score	The PGI-C is a single-item, self-report that requires the participant to assess how much his/her illness has improved or worsened relative to baseline and rate on a 7-point scale: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. A higher score indicates a greater disease progression.	Week 8
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores	The SF-36 is a health-related survey that assesses participant's health status and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health, mental health, social functioning, and vitality. The 8 domains are combined to form 2 component scores: PCS and MCS. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health-related quality of life. 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.	Baseline, Week 8
Change From Baseline in Eating Disorder Examination Questionnaire-7-Item Version (EDE-Q7) Total Score	The EDE-Q7 is a self-report version of the eating disorder examination (EDE) and measures eating-disorder psychopathology in the past 28 days and over longer intervals. It comprises of 3 subscale scores (dietary restraint, shape/weight overvaluation, and body dissatisfaction). An EDE-Q global (total) score is calculated as average of 3 subscale scores and ranges from 0 (absence of the feature) to 6 (extreme degree). A higher score indicates a more severe outcome. LS mean was determined by ANCOVA model with treatment and trial center as fixed factors and baseline value as covariate.	Baseline, Week 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2021
• Primary Completion (Actual): August 19, 2022
• Study Completion (Actual): August 19, 2022

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 29, 2021
• First Posted (Actual): November 9, 2021

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Binge Eating Disorder; Centanafadine
• Additional Relevant MeSH Terms: Mental Disorders; Feeding and Eating Disorders; Binge-Eating Disorder; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 405-201-00056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No