A Trial Evaluating the Long-term Safety and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder

An Open-label, 52-Week, Multicenter Trial Evaluating the Long-term Safety and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder

This study will evaluate the long-term safety and tolerability of centanafadine sustained-release tablets, administered twice daily in the treatment of adults with attention deficit hyperactivity disorder (ADHD).

Study Overview

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

Detailed Description

This open-label study will assess the overall safety and tolerability of 400 mg total daily dose centanafadine sustained-release tablets in subjects, over the course of approximately 52 weeks. This study will accept rollover subjects from both the 405-201-00013 and 405-201-00014 trials. For individuals that did not participate in one of the studies mentioned above, they will be able to enroll if they meet the inclusion criteria as outlined below.

• Study Type: Interventional
• Enrollment (Actual): 660
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Culver City, California, United States, 90230
      • 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

De Novo Subjects [De Novo Enrollment has ended 20Sep2019].

Inclusion Criteria:

• De novo subjects 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.
• Subjects are 18 to 55 years of age, inclusive, at the time of consent.
• Subjects have BMI of 18 to 40, inclusive
• Subjects are willing to discontinue all prohibited psychotropic medications starting from the time of signing the informed consent and up to the 10-day safety follow-up period.

Exclusion Criteria:

• Subject has a DSM-5 diagnosis of Other Specified or Unspecified Attention-Deficit/Hyperactivity Disorder as confirmed by ACDS Version 1.2.
• Subject has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this trial or is uncontrolled and associated with significant symptoms, including but not limited to: a current major depressive episode (per DSM-5 criteria), current symptoms (past 90 days) meeting the DSM-5 criteria for a diagnosis of generalized anxiety disorder, obsessive compulsive disorder, panic disorder, or posttraumatic stress disorder, as established by the MINI. NOTE: Subjects with mild mood or anxiety symptoms that do not meet criteria for diagnosis, who do not require treatment based on the Investigator's assessment, and do not confound efficacy or safety assessments in the opinion of the examining Investigator, may be included.
• Subjects that have a positive alcohol test (via breathalyzer or blood), a positive drug screen for cocaine, or other illicit drugs (excluding marijuana). Subjects with a positive drug screen for confirmed prescription medications at baseline will not be permitted to continue participation in Trial 405-201-00015. NOTE: Subjects that tested positive for marijuana may be permitted to be enrolled if they have no evidence of a substance use disorder, and if they agree to refrain from use for the duration of the trial. Allowance for subjects testing positive for marijuana at screening require explicit approval from the medical monitor.

Rollover Subjects: Rollover Enrollment has ended 28Aug2020.

Inclusion Criteria:

• Subjects who completed the double-blind treatment period and 7-day follow-up after last dose of investigational medicinal product (IMP) in double-blind trials and who, in the opinion of the investigator, could potentially benefit from centanafadine for ADHD.

Exclusion Criteria:

• Subjects who, during the double-blind phase 3 trial experienced, in the opinion of the investigator, poor tolerability to trial medication or whose safety assessments resulted in new concerns that would suggest the subject may not be appropriate for a 52-week treatment with trial medication.
• Subjects who have re-initiated any therapy for adult ADHD during the 7-day follow-up period after the final treatment visit of the double-blind phase 3 trial.
• Subjects that have a positive alcohol test (via breathalyzer or blood), a positive drug screen for cocaine, or other illicit drugs (excluding marijuana). Subjects with a positive drug screen for confirmed prescription medications at baseline will not be permitted to continue participation in Trial 405-201-00015. NOTE: Subjects that test positive for marijuana may not be permitted to rollover into the open label study, and must agree to refrain from use for the duration of the open label trial. Allowance for subjects testing positive for marijuana at time of rollover requires explicit approval from the medical monitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Centanafadine; 400 mg total daily dose	Drug: Centanafadine SR; 200 mg, BID, oral tablets; Other Names: EB-1020

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event (AE) Reporting	Frequency and severity of treatment-emergent adverse events (TEAEs) will be assessed to determine safety and tolerability of centanafadine SR tablets	Up to 52 weeks or early termination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adult ADHD Investigator Symptom Rating Scale (AISRS)	18-item scale with a total score range of 0 to 54 points. Composed of 2 subscales that can range from 0 to 27 points. A higher value represents a worse outcome. Efficacy endpoint. Results will be assessed to determine effectiveness of drug.	Up to 52 weeks or early termination
Clinical Global Impression-Severity of Illness Scale (CGI-S)	An observer-rated scale with a total score range of 0 to 7. A higher score represents a worse outcome.Efficacy endpoint. Results will be assessed to determine effectiveness of drug.	Up to 52 weeks or early termination
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 52 weeks or early termination

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Actual): September 7, 2021
• Study Completion (Actual): September 7, 2021

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): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

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: 405-201-00015

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 an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
• 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