A Trial to Evaluate the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder

A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder

This study evaluated the efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with ADHD. Participants either received a twice-daily dose of centanafadine sustained-release tablets, or twice-daily placebo.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder; Attention Deficit Disorder
• Intervention / Treatment: Drug: Centanafadine SR; Other: Placebo; Drug: Centanafadine SR

Detailed Description

Screening & Washout Period: up to 28 days Investigational Treatment Period: 49 days Follow-up Period : 7 days or 10 days

• Study Type: Interventional
• Enrollment (Actual): 590
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • For additional information regarding sites, contact 844-687-8522

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must meet the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for ADHD (including predominantly inattentive presentation, hyperactive presentation, or combined presentation) as confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) Version 1.2. To confirm that ADHD is the primary diagnosis, the Mini International Neuropsychiatric Interview (MINI) will be used to identify and exclude other psychiatric conditions which would preclude enrollment.
• Participants who were not receiving any pharmacological treatment for ADHD must have an Adult ADHD Investigator Symptom Rating Scale (AISRS) score of ≥ 28 at screening and baseline. Participants who were receiving pharmacological treatment for ADHD at screening must have a minimum AISRS score of ≥ 22 at screening, and a score of ≥ 28 at baseline.
• All participants must be willing to discontinue all prohibited psychotropic medications starting from the time of signing the informed consent through the 7-day follow-up period. Participants that do not rollover into Trial 405-201-00015 must be willing to discontinue all prohibited psychotropic medications starting from the time of signing the informed consent until after the follow-up telephone call 10 days after the last dose of IMP.
• Participants must have a Clinical Global Impression-Severity of Illness Scale (CGI-S) score of ≥ 4 (≥ moderate impairment) at baseline.

Exclusion Criteria:

• Participant has a DSM-5 Diagnosis of Other Specified or Unspecified Attention Deficit/Hyperactivity Disorder.
• Participant has a current comorbid psychiatric disorder that either could be expected to require treatment with medications prohibited in this trial, or to confound efficacy or safety assessments. Examples include, but are not limited to, psychotic disorder, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, a current major depressive episode, or posttraumatic stress disorder, as established by the MINI.
• In the opinion of the investigator, participants has not derived significant therapeutic benefit from 2 or more ADHD therapies of 2 different classes (eg, amphetamine and methylphenidate) given with an acceptable dose and duration of adulthood (aged 18 or older). NOTE: If participants has not derived significant therapeutic benefit due to an inability to tolerate side effects, eligibility can be discussed on case-by-case basis with the medical monitor.
• Participants who have a positive alcohol test (via breathalyzer or blood), a positive drug screen assessed prior to the baseline visit for cocaine, other illicit drugs (including marijuana), or prescription or OTC ADHD medications will be early terminated. This includes medications such as opioids or benzodiazepines taken without prescription.
• In the opinion of the investigator, the participants is unable to adhere to the treatment regimen or other requirements outlined in the protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-blind Run-in Period: Placebo; Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).	Other: Placebo; BID, oral tablet
Experimental: Double-blind Treatment Period: Centanafadine SR 200 mg; Following Single-blind Run-in Period, participants with <30% improvement on Adult ADHD Self Report Scale (ASRS) scale score were randomized to receive centanafadine 200 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Drug: Centanafadine SR; 200 mg, BID, oral tablets; Other Names: EB-1020; Drug: Centanafadine SR; 100 mg, BID, oral tablets; Other Names: EB-1020
Experimental: Double-blind Treatment Period: Centanafadine SR 400 mg; Following Single-blind Run-in Period, participants with <30% improvement on Adult ADHD Self Report Scale (ASRS) scale score were randomized to receive centanafadine 400 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Drug: Centanafadine SR; 200 mg, BID, oral tablets; Other Names: EB-1020; Drug: Centanafadine SR; 100 mg, BID, oral tablets; Other Names: EB-1020
Placebo Comparator: Double-blind Treatment Period: Placebo; Following Single-blind Run-in Period, participants with <30% improvement on Adult ADHD Self Report Scale (ASRS) scale score were randomized to receive centanafadine SR matching placebo tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Other: Placebo; BID, oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS) Score at Day 42	The AISRS is an 18-item clinician rating scale to evaluate individual ADHD symptoms on a scale of 0 (none) to 3 (severe). The total sum ranges from 0 (no ADHD symptoms) to 54 (extremely severe ADHD symptoms). Mixed-effect model repeated measure (MMRM) was used for the analysis.	Baseline and Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Day 42	CGI-S is an observer-rated scale used to measure symptom severity with a total score range of 0 to 7 where 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. A negative change from Baseline indicates improvement. MMRM was used for the analysis.	Baseline and Day 42

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event Reporting	Frequency and severity of treatment-emergent adverse events (TEAEs) will be assessed to determine safety and tolerability of centanafadine SR tablets	Up to 59 days
ADHD Impact Module - Adult (AIM-A)	Scale composed of 3 subscales with a maximum score of 100. A lower score indicates a worse outcome. Exploratory endpoint; comparison of baseline score to other points throughout the study.	Up to 42 days
Adult ADHD Self Report Scale (ASRS)	An 18 question report, total score ranges from 0 to 124. A higher score denotes a worse outcome. Exploratory endpoint; comparison of baseline score to other points throughout the study	Up to 42 days
AISRS	Change from baseline total score compared to every scheduled visit. Each subscale is composed of 9 items each. Scores can range from 0 to 27, with a higher score representing a worse outcome. Change from baseline scores are compared to every scheduled visit score.	Up to 42 days

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2019
• Primary Completion (Actual): May 14, 2020
• Study Completion (Actual): May 14, 2020

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 30, 2018

Study Record Updates

• Last Update Posted (Actual): October 18, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: ADHD; ADD; Centanafadine
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: 405-201-00014

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; Statistical Analysis Plan (SAP); Clinical Study Report (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