Study of Flexible Doses of the Triple Reuptake Inhibitor EB-1020 Sustained Release (SR) in the Treatment of Adult Males With Attention-Deficit Hyperactivity Disorder

NCT01939353 | Completed Phase 2 Results FDA Drug

• 1 other identifier: EB-1020-SR-ADHD-201
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

This was a Phase 2 exploratory study to evaluate the efficacy and safety of EB-1020 SR (centanafadine sustained release \[CTN SR\]) in treating participants who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for Attention-Deficit Hyperactivity Disorder (ADHD) on the Mini International Neuropsychiatric Interview Plus, Version 6.0 (M.I.N.I.-Plus). Evaluations included determining an effectiveness signal for ADHD and related symptoms and exploring dosing, tolerability, onset of action, and duration of effect. Dose-response/tolerability relationships with CTN SR were also explored. The 1-week placebo run-in \[single-blind (SB)\] was also used for informal safety comparison purposes.

Conditions

Adult ADHD

Keywords

Adult ADHD; centanafadine sustained release

Outcome Measures

Primary Outcomes (1)

• Change From Baseline-2 in ADHD Symptoms to Week 4 as Assessed by the Adult Attention-Deficit Hyperactivity Disorder Rating Scale (AD HD-RS-IV)

  The ADHD-RS-IV consists of 18 items with first 9 items assessing inattentive symptoms and the last 9 items assessing hyperactive-impulsive symptoms scored on a 4-point Likert-type severity scale with 0 (none), 1 (mild), 2 (moderate), and 3 (severe) with a total score ranging from 0 to 54. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.

  Baseline, Week 4

Secondary Outcomes (13)

• Change From Baseline-2 in ADHD Symptoms as Assessed by the Adult ADHD-RS-IV

  Baseline-2, Weeks 1, 2, 3, and 6 (Follow-up Visit)

• Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale

  Baseline-2 and Week 4

• Percentage of Participants Who Are Responders for ADHD Symptoms as Measured by the ADHD-RS-IV

  Baseline-2, Weeks 1, 2, 3, and 4

• Percentage of Participants Who Are High Responders for ADHD Symptoms as Measured by the ADHD-RS-IV

  Baseline-2, Weeks 1, 2, 3, and 4

• Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV

  Baseline-2, Weeks 1, 2, 3 and 4

Study Arms (1)

Centanafadine SR 100-500 mg

EXPERIMENTAL

Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received centanafadine (CTN) 100 mg, sustained release (SR) tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.

Drug: CTN SR; Drug: Placebo

Interventions

CTN SR DRUG

CTN SR tablets

Also known as: EB-1020 SR

Centanafadine SR 100-500 mg

Placebo DRUG

CTN SR-matching placebo tablets

Centanafadine SR 100-500 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants had to be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use.
• Participants must have met DSM-IV-TR diagnostic criteria for ADHD (Combined, Predominantly Inattentive or Predominantly Hyperactive-Impulsive Types) on the M.I.N.I.-Plus.
• Participants must have had an ADHD-RS-IV score of greater than or equal to 28 at the placebo run-in baseline and CTN SR treatment baseline.
• Participants must have had a Clinical Global Impression of Severity (ADHD version) score of greater than or equal to 4.
• Participants must be able to read well enough to understand the informed consent form and other participant materials.
• Participants must have been able to be reliably rated on the psychiatric scales required by the protocol based on investigator's judgment.
• Participants must have been able to read and understand English.
• Participants must have had a body mass index of approximately 18 to 35 kilograms/meter squared.
• Sexually active, fertile males must have used effective birth control if their partners were women of childbearing potential. Women of childbearing potential (if a partner of a male participant) included any female who had experienced menarche and who had not undergone successful surgical sterilization or women on hormone replacement therapy with documented serum follicle stimulating hormone level greater than 35 milli-international units/milliliter. Even women who were using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or were practicing abstinence or where the partner was sterile (for example, vasectomy), should have been considered to be of childbearing potential.

You may not qualify if:

• Participant had a DSM-IV-TR diagnosis of ADHD not otherwise specified.
• Participants rated as having a greater than or equal to 30% improvement in ADHD symptoms or a score of less than 28 on the ADHD-RS-IV after Week 1 (placebo run-in). Such participants were withdrawn from the study prior to receiving any active drug.
• Participant had a current or lifetime history of bipolar disorder or any psychotic disorder as established by M.I.N.I.-Plus.
• Participant had a current history (past 90 days) of major depression, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder or post-traumatic stress disorder as established by the M.I.N.I.-Plus.
• History in the past 20 years of electroconvulsive therapy or lifetime history of vagal nerve stimulation or deep brain stimulation for the treatment of depression.
• Participants with a history of drug or alcohol use disorders (abuse or dependence) must have been free of the diagnosis and of substance use for at least 6 months prior to the Screening visit.
• Participant had a history of epilepsy, seizures, syncope, unexplained blackout spell(s), head trauma with clinically significant loss of consciousness or noninfantile febrile seizures.
• Participant had a currently active medical condition (other than ADHD) that, in the opinion of the investigator, could have interfered with the ability of the participant to participate in the study safely.
• Participant had a history of clinically significant, diagnosed cardiovascular disease of any kind, including uncontrolled hypertension. Participant had newly diagnosed cardiovascular disease of any kind in the investigator's judgment.
• The participant had an intelligence quotient less than 80.
• In the opinion of the investigator, the participant had not derived significant therapeutic benefit from 2 or more ADHD therapies given with an adequate dose and duration in adulthood (age 18 or older); that is, 1 failed course of treatment was acceptable, but 2 failed courses of treatment were not acceptable.
• Participant taking medication specifically for treatment of ADHD symptoms (for example, stimulants, atomoxetine, tricyclic antidepressants, bupropion, modafinil) must have been off stimulants for 2 weeks and off nonstimulant ADHD therapies for 3 weeks prior to the placebo run-in visit and must have returned to the baseline level of ADHD symptoms in the opinion of the investigator. Participants must not have had evidence of a discontinuation or withdrawal reaction.
• Participant was currently taking any antidepressant medication for any condition.
• Participant was currently taking antipsychotic medication or an anticonvulsant medication (for example, phenytoin, carbamazepine, lamotrigine, or valproic acid) at anticonvulsant doses.
• Participant had a known history of allergy to CTN.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (3)

Unknown Facility

Bradenton, Florida, 34201, United States

Location

Unknown Facility

Maitland, Florida, 32751, United States

Location

Unknown Facility

Las Vegas, Nevada, 89128, United States

Location

Related Links

• Otsuka Clinical Trial Website
• Otsuka Clinical Trial Transparency

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This was a single-blind trial in which participants were blinded to investigational product throughout the trial. Participants were not informed of the exact timing of CTN SR versus placebo treatment, in order to maintain the blinded nature of the placebo treatment and reduce potential placebo effects.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 11, 2013
• Study Start: October 3, 2013
• Primary Completion: February 20, 2014
• Study Completion: February 20, 2014
• Last Updated: April 30, 2026
• Results First Posted: October 18, 2021

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• 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 the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

US (3)