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

• ClinicalTrials.gov Identifier: NCT03605836
• Recruitment Status: Completed
• First Posted: July 30, 2018
• Last Update Posted: October 19, 2020
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description

Brief Summary:

This study evaluates the efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with ADHD. Patients will either receive a twice-daily dose of centanafadine sustained-release tablets, or twice-daily placebo.

Condition or disease	Intervention/treatment	Phase
Attention Deficit Disorder; Attention Deficit Hyperactivity Disorder	Drug: Centanafadine SR; Other: Placebo	Phase 3

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 440 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 16, 2019
• Actual Primary Completion Date: May 14, 2020
• Actual Study Completion Date: May 14, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Centanafadine Treatment 1; Total daily dose of 200 mg	Drug: Centanafadine SR; 100 mg, BID, oral tablets; Other Name: EB-1020
Experimental: Centanafadine Treatment 2; Total daily dose of 400 mg	Drug: Centanafadine SR; 200 mg, BID, oral tablets; Other Name: EB-1020
Placebo Comparator: Placebo	Other: Placebo; BID, oral tablet

Outcome Measures

Primary Outcome Measures :

1. Adult ADHD Investigator Symptom Rating Scale (AISRS) [ Time Frame: Up to 49 days or early termination ]
   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. Change from baseline in AISRS total score to assess efficacy.

Secondary Outcome Measures :

1. Clinical Global Impression-Severity of Illness Scale (CGI-S) [ Time Frame: Up to 42 days or early termination ]
   An observer-rated scale with a total score range of 0 to 7. A higher score represents a worse outcome. Change from baseline to assess efficacy

Other Outcome Measures:

1. Adverse Event Reporting [ Time Frame: Up to 77 days or early termination ]
   Frequency and severity of treatment-emergent adverse events (TEAEs) will be assessed to determine safety and tolerability of centanafadine SR tablets
2. ADHD Impact Module - Adult (AIM-A) [ Time Frame: Up to 49 days or early termination ]
   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.
3. Adult ADHD Self Report Scale (ASRS) [ Time Frame: Up to 77 days or early termination ]
   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
4. AISRS [ Time Frame: Up to 77 days or early termination ]
   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.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• 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 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. Subjects 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 subjects 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. Subjects 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.
• Subjects must have a Clinical Global Impression-Severity of Illness Scale (CGI-S) score of ≥ 4 (≥ moderate impairment) at baseline.

Exclusion Criteria:

• Subject has a DSM-5 Diagnosis of Other Specified or Unspecified Attention Deficit/Hyperactivity Disorder.
• Subject 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, subject 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 subject 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.
• Subjects 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 subject is unable to adhere to the treatment regimen or other requirements outlined in the protocol.

Contacts and Locations

Locations

United States, Florida

For additional information regarding sites, contact 844-687-8522

Orlando, Florida, United States, 32806

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

More Information

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT03605836
• Other Study ID Numbers: 405-201-00014
• First Posted: July 30, 2018
• Last Update Posted: October 19, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• 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.
• 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
• URL: https://clinical-trials.otsuka.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Centanafadine; ADD; ADHD

Additional relevant MeSH terms:

Hyperkinesis; Disease; Attention Deficit Disorder with Hyperactivity; Pathologic Processes; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases