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

Primary Purpose

Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Centanafadine SR
Placebo
Centanafadine SR
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Attention Deficit Disorder focused on measuring Centanafadine, ADD, ADHD

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Single-blind Run-in Period: Placebo

Double-blind Treatment Period: Centanafadine SR 200 mg

Double-blind Treatment Period: Centanafadine SR 400 mg

Double-blind Treatment Period: Placebo

Arm Description

Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 28, 2018
Last Updated
September 20, 2021
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03605836
Brief Title
A Trial to Evaluate the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
January 16, 2019 (Actual)
Primary Completion Date
May 14, 2020 (Actual)
Study Completion Date
May 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

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

5. Study Description

Brief Summary
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.
Detailed Description
Screening & Washout Period: up to 28 days Investigational Treatment Period: 49 days Follow-up Period : 7 days or 10 days

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder
Keywords
Centanafadine, ADD, ADHD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
590 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single-blind Run-in Period: Placebo
Arm Type
Experimental
Arm Description
Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).
Arm Title
Double-blind Treatment Period: Centanafadine SR 200 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Double-blind Treatment Period: Centanafadine SR 400 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Double-blind Treatment Period: Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Centanafadine SR
Other Intervention Name(s)
EB-1020
Intervention Description
100 mg, BID, oral tablets
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
BID, oral tablet
Intervention Type
Drug
Intervention Name(s)
Centanafadine SR
Other Intervention Name(s)
EB-1020
Intervention Description
200 mg, BID, oral tablets
Primary Outcome Measure Information:
Title
Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS) Score at Day 42
Description
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.
Time Frame
Baseline and Day 42
Secondary Outcome Measure Information:
Title
Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Day 42
Description
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.
Time Frame
Baseline and Day 42
Other Pre-specified Outcome Measures:
Title
Adverse Event Reporting
Description
Frequency and severity of treatment-emergent adverse events (TEAEs) will be assessed to determine safety and tolerability of centanafadine SR tablets
Time Frame
Up to 59 days
Title
ADHD Impact Module - Adult (AIM-A)
Description
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.
Time Frame
Up to 42 days
Title
Adult ADHD Self Report Scale (ASRS)
Description
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
Time Frame
Up to 42 days
Title
AISRS
Description
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.
Time Frame
Up to 42 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
For additional information regarding sites, contact 844-687-8522
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://clinical-trials.otsuka.com

Learn more about this trial

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

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