Attention Deficit DisorderPhase 3NCT03605680

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

A Phase 3 study testing Centanafadine SR in people with Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study evaluates the efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with attention-deficit/hyperactivity disorder (ADHD). Participants will either receive a twice-daily dose of centanafadine sustained-release tablets, or twice-daily placebo. Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder
What is being tested?: Centanafadine SR
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 604 participants
Where: 1 siteUnited States
Study dates: 16 Jan 2019to 11 Apr 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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 (NCT03605849) 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 investigational medicinal product (IMP).
Participants must have a Clinical Global Impression-Severity of Illness Scale (CGI-S) score of ≥ 4 (≥ moderate impairment) at baseline.

Who cannot join

Participants with a DSM-5 diagnosis of Other Specified or Unspecified Attention Deficit/Hyperactivity Disorder.
Participants 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 International Neuropsychiatric Interview (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 during 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 over-the-counter (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.

Trial locations and contacts

1 site in 1 country.

United States1 site

For additional information regarding sites, contact 844-687-8522
New York, New York, 10022

Other trials in United States

About this study

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

Read the detailed description

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

Conditions: Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder
Being tested: Centanafadine SR, Placebo
Keywords: Centanafadine, ADHD, ADD
Medical subject headings: Attention Deficit Disorder with Hyperactivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Centanafadine SRDrug
Also called EB-1020
100 mg, BID, oral tablets
PlaceboOther
BID, oral tablet.
Centanafadine SRDrug
Also called EB-1020
200 mg, BID, oral tablets

Study groups in NCT03605680
Study group	Role	What they receive
Single-blind Run-in Period: Placebo	Experimental	Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1). Receives: Other: Placebo
Double-blind Treatment Period: Centanafadine SR 200 mg	Experimental	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. Receives: Drug: Centanafadine SR
Double-blind Treatment Period: Centanafadine SR 400 mg	Experimental	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. Receives: Drug: Centanafadine SR
Double-blind Treatment Period: Placebo	Placebo comparator	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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS)
The Adult Investigator Symptom Rating Scale (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). Negative change from Baseline indicates improvement. Mixed-effect model repeated measure (MMRM) was used for analysis.
Measured: Baseline and Day 42

Secondary outcomes (1)

Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S)
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.
Measured: Baseline and Day 42

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 201911 Apr 2020

First posted30 Jul 2018
Study start16 Jan 2019
Primary completion11 Apr 2020
Study completion11 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Attention Deficit DisorderStudies of the same condition, open and under way.
More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 604 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03605680
Sponsor's protocol ID: 405-201-00013
Status last verified: Feb 2022
First submitted: 28 Jun 2018
Last updated: 15 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03605680
Acronym / sponsor ID: 405-201-00013
Conditions: Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder
Keywords: Centanafadine, ADHD, ADD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 604 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
Study start: 16 Jan 2019 (actual)
Primary completion: 11 Apr 2020 (actual)
Study completion: 11 Apr 2020 (actual)
First posted: 30 Jul 2018 (actual)
Results: Posted 5 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Single-blind Run-in Period: Placebo	Experimental	Other: PlaceboPlacebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).
Double-blind Treatment Period: Centanafadine SR 200 mg	Experimental	Drug: Centanafadine SRFollowing 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.
Double-blind Treatment Period: Centanafadine SR 400 mg	Experimental	Drug: Centanafadine SRFollowing 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.
Double-blind Treatment Period: Placebo	Placebo comparator	Other: PlaceboFollowing 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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 (NCT03605849) 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 investigational medicinal product (IMP).
Participants must have a Clinical Global Impression-Severity of Illness Scale (CGI-S) score of ≥ 4 (≥ moderate impairment) at baseline.

Key exclusion criteria (5 listed)

Participants with a DSM-5 diagnosis of Other Specified or Unspecified Attention Deficit/Hyperactivity Disorder.
Participants 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 International Neuropsychiatric Interview (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 during 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 over-the-counter (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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Centanafadine SRAlso: EB-1020100 mg, BID, oral tablets	Drug	Double-blind Treatment Period: Centanafadine SR 200 mg
PlaceboBID, oral tablet.	Other	Double-blind Treatment Period: Placebo, Single-blind Run-in Period: Placebo
Centanafadine SRAlso: EB-1020200 mg, BID, oral tablets	Drug	Double-blind Treatment Period: Centanafadine SR 400 mg

Primary outcome

Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS)
Time frame: Baseline and Day 42
The Adult Investigator Symptom Rating Scale (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). Negative change from Baseline indicates improvement. Mixed-effect model repeated measure (MMRM) was used for analysis.

1 secondary outcome

Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S)
Time frame: Baseline and Day 42

Results and safety

Results posted to the registry on 5 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Single-blind (SB) Run-in Period: Placebo	604	466
Double-blind Treatment Period: Centanafadine SR 200 mg	0	0
Double-blind Treatment Period: Centanafadine SR 400 mg	0	0
Double-blind Treatment Period: Placebo	0	0

Primary outcome: Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS)

Time frame: Baseline and Day 42. Least squares mean (Standard Error). Unit: score on a scale

Measure	Double-blind Treatment Period: Centanafadine SR 200 mg n = 147	Double-blind Treatment Period: Centanafadine SR 400 mg n = 147	Double-blind Treatment Period: Placebo n = 144
Value	-10.1 (0.99)	-9.73 (0.98)	-6.98 (0.98)

Double-blind Treatment Period: Centanafadine SR 200 mg vs Double-blind Treatment Period: Placebo: Least Squares (LS ) Mean Difference: -3.15 (95% CI -5.79 to -0.51), p =0.0193, MMRM
Double-blind Treatment Period: Centanafadine SR 400 mg vs Double-blind Treatment Period: Placebo: LS Mean Difference: -2.74 (95% CI -5.35 to -0.14), p =0.0392, MMRM

Population analysed: Efficacy sample FAS included all participants in the safety sample who had a Baseline value and at least one valid post-randomization efficacy evaluation for AISRS total score in the Double-blind Treatment Period. Overall number analysed are the participants with data available for analysis.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 59 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo: SB Run-in Period Only	0 of 138 (0%)	2 of 138 (1.4%)	0 of 138
Placebo + Centanafadine SR 200 mg	2 of 149 (1.3%)	25 of 149 (16.8%)	0 of 149
Placebo + Centanafadine SR 400 mg	0 of 149 (0%)	22 of 149 (14.8%)	0 of 149
Placebo + Placebo	0 of 148 (0%)	18 of 148 (12.2%)	0 of 148

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. 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.

Related trials for Attention Deficit Disorder

Enrolling by invitationPhase 3
An Open-Label Study to Assess the Long-Term Safety of Solriamfetol in Children and Adolescents With ADHD
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Not yet recruitingPhase 2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS) (time frame: Baseline and Day 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03605680.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.