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

Phase 2
Completed
Conditions
Binge-Eating Disorder
Interventions
Drug: Placebo
Registration Number
NCT05113953
Lead Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
147
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Centanafadine 400 mgCentanafadineParticipants will receive centanafadine 200 mg SR tablets, orally, twice daily (BID) at a TDD of 400 mg for 8 weeks.
Centanafadine 200 mgCentanafadineParticipants 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.
Centanafadine 200 mgPlaceboParticipants 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.
PlaceboPlaceboParticipants will receive centanafadine matching placebo tablets, orally, BID for 8 weeks.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Number of Binge Eating Days Per WeekBaseline, Weeks 7 to 8

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total ScoreBaseline, Week 8

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.

Change From Baseline in Clinical Global Impression - Severity (CGI-S) ScoreBaseline, Week 8

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.

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

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.

Study Medication Withdrawal Questionnaire (SMWQ) Total Mean ScoreWeek 8

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.

Number of Participants With Suicidality as Measured by Columbia Suicide Severity Rating Scale (C-SSRS) ScoreWeek 8

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.

Number of Participants With Potentially Clinically Relevant Laboratory AbnormalitiesFrom first dose of study drug up to 1 week post last dose (Up to 9 weeks)

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.

Number of Participants With Potentially Clinically Relevant Vital Sign AbnormalitiesFrom first dose of study drug up to 1 week post last dose (Up to 9 weeks)

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.

Number of Participants With Potentially Clinically Relevant 12-Lead Electrocardiogram (ECG) AbnormalitiesFrom first dose of study drug up to 1 week post last dose (Up to 9 weeks)

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).

Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total ScoreBaseline, Week 8

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.

Trial Locations

Locations (25)

NoesisPharma, LLC

🇺🇸

Phoenix, Arizona, United States

Southern California Research LLC

🇺🇸

Beverly Hills, California, United States

Pharmacology Research Institute - San Fernando Valley

🇺🇸

Encino, California, United States

Collaborative Neuroscience Research, LLC

🇺🇸

Garden Grove, California, United States

Pacific Clinical Research Management Group LLC

🇺🇸

Upland, California, United States

Mountain View Clinical Research, LLC

🇺🇸

Denver, Colorado, United States

Clinical Neuroscience Solutions - Jacksonville

🇺🇸

Jacksonville, Florida, United States

Miami Dade Medical Research Institute

🇺🇸

Miami, Florida, United States

iResearch Atlanta

🇺🇸

Decatur, Georgia, United States

Psych Atlanta, PC

🇺🇸

Marietta, Georgia, United States

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NoesisPharma, LLC
🇺🇸Phoenix, Arizona, United States

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