Clinical trial NCT06973577: A Trial of Centanafadine Efficacy and Safety in Adults With Attention-deficit/Hyperactivity Disorder and Comorbid Anxiety
Official title: Phase 3b, Randomized, Double-blind, 8-week, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Centanafadine Once Daily Extended-release Capsules for the Treatment of Adults With Attention-deficit/Hyperactivity Disorder and Comorbid Anxiety
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: ADHD
Anxiety
Generalized Anxiety
Social Anxiety Disorder
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-15
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase 3b, Randomized, Double-blind, 8-week, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Centanafadine Once Daily Extended-release Capsules for the Treatment of Adults with Attention-deficit/Hyperactivity Disorder and Comorbid Anxiety


Eligibility criteria: Inclusion Criteria:

1. Participants between 18 and 65 years of age, inclusive.
2. Diagnosis of ADHD per the DSM-5 criteria and confirmed using the ACDS Version 1.2 at screening.
3. AISRS total score of ≥ 28 at baseline.
4. Diagnosis of GAD or SAD per DSM-5 criteria and confirmed using the MINI at screening.
5. HAM-A total score ≥ 20 at baseline.
6. CGI-S-ADHD and CGI-S-anxiety rating ≥ 4 at baseline.
7. Body mass index from 18.0 to 40.0 kg/m2 (inclusive).
8. Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

Exclusion Criteria:

1. In the clinical opinion of the investigator, participant has not derived significant therapeutic benefit from 2 or more ADHD therapies of 2 different classes (eg, amphetamine and methylphenidate, or amphetamine and atomoxetine) given with an acceptable dose and duration during adulthood (aged 18 years or older).
2. In the opinion of the investigator, participant has not derived significant therapeutic benefit from 2 or more anxiety therapies of 2 different classes (eg, selegiline and duloxetine, or buspirone and lorazepam) given with an acceptable dose and duration during adulthood (aged 18 years or older).
3. Current use of prohibited psychotropic medications that cannot be discontinued 2 weeks prior to randomization. Fluoxetine is prohibited within 28 days of randomization.
4. Subjects who have started individual or group psychotherapy within the past 3 months prior to screening (ongoing psychotherapy that is not expected to change in frequency or type during the trial is permissible).
5. Any disorder that is the primary focus of treatment other than ADHD.
6. Psychosis, bipolar disorder, MDD, post-traumatic stress disorder, dementia, obsessive compulsive disorder, personality disorders, substance/medication induced anxiety, anxiety disorder due to another medical condition, specific phobia if this is the primary reason for treatment, selective mutism.
7. Participant is, in the investigator's judgment, at significant risk for suicide. A participant with a Columbia-Suicide Severity Rating Scale (C-SSRS) ideation score of 4 or 5 within the last 6 months or participants who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) within the past year must be excluded.
8. Participants with a positive drug test at baseline for ADHD and anxiety medication including methylphenidate, amphetamine, or for drugs of abuse. Participants with a positive drug screen for confirmed prescription or over-the-counter (OTC) use of ADHD and anxiety medications at screening will be required to undergo a washout period.
9. Participants with evidence of current substance use disorder or history in the past 12 months.
10. Participants with epilepsy, a history of epilepsy, or a history of seizure, except for a single childhood febrile seizure, a single seizure post brain injury, or a single seizure due to alcohol withdrawal.
11. Participants who are partially hospitalized or receiving inpatient care or have any other medical or physical condition(s) that, in the opinion of the investigator, may prevent the participant from completing the trial or would go against the participant's best interest with participation in the trial. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol.
12. The following laboratory test and ECG results are exclusionary at screening:

    1. Platelets ≤ 75,000/mm3
    2. Hemoglobin ≤ 9 g/dL
    3. Neutrophils, absolute ≤ 1000/mm3
    4. AST \> 2 × upper limit of normal
    5. ALT \> 2 × upper limit of normal
    6. Creatinine ≥ 2 mg/dL
    7. HbA1c ≥ 7%
    8. QTcF ≥ 450 msec for males or ≥ 470 msec for females
    9. Abnormal free thyroxin (T4), unless discussed with and approved by the medical monitor (Note: free T4 is measured only if result for thyroid stimulating hormone \[TSH\] is abnormal)
13. Participants presenting with, or having a history of, uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 95 mmHg) or symptomatic hypotension, or orthostatic hypotension which is defined as a decrease of ≥ 30 mmHg in systolic blood pressure or a decrease of ≥ 20 mmHg in diastolic blood pressure after at least 3 minutes standing compared with the previous supine blood pressure, or development of symptoms.
14. Participants with a history of any prior exposure to centanafadine.
15. Participants who have participated in other clinical trials involving investigational drugs within 180 days prior to screening or who have participated in more than 2 interventional clinical trials involving investigational drugs within the past year.
16. Participants of childbearing potential who are breast-feeding and/or have a positive pregnancy test result prior to receiving IMP.
17. Participants of reproductive potential / POCBP who do not agree to practice 2 different highly effective methods of birth control or remain fully abstinent from sexual activity with the potential for conception, per the guidelines in Section 10.3.
18. Participants who do not agree to refrain from donating sperm or eggs from trial screening through 90 days for sperm and 30 days for eggs after the last dose of IMP.
19. Participants who have an allergy to the IMP or any component of the IMP.

Primary outcomes:
measure: Change in Adult Investigator Symptom Rating Scale (AISRS)
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Change in Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: Baseline to Week 8
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Clinical Research Site #017 - Harmonex Neuroscience Research
state: Alabama
city: Orange
country: United States
facility: Clinical Research Site #011 - NRC Research Institute
state: California
city: Jacksonville
country: United States
facility: Clinical Research Site #005 - Clinical Neuroscience Solutions, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Research Site #006 - CNS Healthcare Orlando
state: Florida
city: Las Vegas
country: United States
facility: Clinical Research Site #016 - Clinical Research of Southern Nevada, LLC
state: Nevada
city: New York
country: United States
facility: Clinical Research Site #021 - The Medical Research Network, LLC
state: New York
city: Memphis
country: United States
facility: Clinical Research Site #001 - CNS Healthcare - Memphis
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Research Site #012 - Clinical Trials of Texas
state: Texas
Study officials:
References: