A Trial to Assess the Pharmacokinetics, Safety, and Tolerability of Centanafadine in Pediatric Subjects With Attention-deficit/Hyperactivity Disorder

Study Overview
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Brief Summary
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This trial will evaluate the pharmacokinetics, safety, and tolerability of centanafadine in pediatric subjects with ADHD.

Official Title
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A Phase 1b, Multicenter, Open-label, Multiple Ascending Dose Trial to Assess the Pharmacokinetics, Safety and Tolerability of Centanafadine Extended-release Capsules After Oral Administration in Pediatric Subjects (4 to 12 Years, Inclusive) With Attention-deficit/Hyperactivity Disorder

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Centanafadine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 4 to 12 years of age, inclusive, at the time of informed consent/assent. Subjects must weight ≥ 13 kg. Subjects with a diagnosis of any ADHD subtype based on Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and confirmed by the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-Kid). Subject is judged by the investigator to be clinically stable, and has not had any psychiatric hospitalizations within the past 12 weeks. Subjects and their caregivers must be able and willing to utilize the AiCure Platform for each daily dose. Exclusion Criteria: Subjects with a clinical presentation or history that is consistent with delirium, dementia, amnesia, or other cognitive disorders; subjects with psychiatric symptoms that are better accounted for by another psychiatric or general medical condition(s) or direct effect of a substance. Subjects with developmental disorders, such as Autism Spectrum Disorder. Subjects with a history of at least mild intellectual disability as determined by IQ < 70, clinical evidence, or a social or school history that is suggestive of intellectual disability. Subjects with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least 90 days prior to first dose of IMP) or an abnormal result for free T4 at screening. Subjects who currently have clinically significant neurological, dermatological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders such as any history of myocardial infarction, congestive heart failure, HIV seropositive status/AIDS, or chronic hepatitis B or C. Subjects with insulin dependent diabetes mellitus (i.e. any subjects using insulin) Subjects with epilepsy, Tourette's Disorder, or a history of seizures or a history of severe head trauma or cerebrovascular disease. Any major surgery within 30 days prior to the first dose of IMP. Any history of significant bleeding or hemorrhagic tendencies. Blood transfusions within 30 days prior to the first dose of IMP. Subjects who have supine or standing diastolic blood pressure, after resting for at least 5 minutes, > 80 mmHg. Subjects who participated in a clinical trial and were exposed to IMP within the last 30 days prior to screening or who participated in more than 2 interventional clinical trials within the past year. Subjects who have had any previous exposure to centanafadine. Subjects with a history of true allergic response to a medication or a history of dermatologic adverse reactions or anaphylaxis secondary drug exposure. Subjects with a history of allergic reaction or known or suspected sensitivity to any substance that is contained in the IMP formulation. Subjects who do not tolerate venipuncture or have poor venous access that would cause difficulty for collecting blood samples. Consumption of alcohol and/or food and beverages containing methylxanthines, foods known to affect CYP1A2 (e.g. charbroiled or pan-fried meats and cruciferous vegetables) within 72 hours prior to dosing. Relative of the trial site employees cannot participate in the trial. Siblings, other family members, and those having the same place of residence as the subject are also excluded from the trial.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (9-12 y)<br>Centanafadine extended release capsule; 100 mg adult equivalent; twice daily for 14 days | Drug: Centanafadine<br>* Extended release capsule<br>|
| Experimental: Cohort 2 (9-12 y)<br>Centanafadine extended release capsule; 200 mg adult equivalent; twice daily for 14 days | Drug: Centanafadine<br>* Extended release capsule<br>|
| Experimental: Cohort 3 (9-12 y)<br>Centanafadine extended release capsule; 400 mg adult equivalent; twice daily for 14 days | Drug: Centanafadine<br>* Extended release capsule<br>|
| Experimental: Cohort 4 (6-8 y)<br>Centanafadine extended release capsule; 100 mg adult equivalent; twice daily for 14 days | Drug: Centanafadine<br>* Extended release capsule<br>|
| Experimental: Cohort 5 (4-5 y)<br>Centanafadine extended release capsule; 100 mg adult equivalent; twice daily for 14 days | Drug: Centanafadine<br>* Extended release capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal peak plasma concentration (Cmax) |  | 24 hours | 
| Area under the concentration-time curve from time 0 to 24 hours (AUC0-24h) on day 14 |  | 24 hours | 
| Apparent clearance and apparent volume of distribution of centanafadine on Day 14 |  | 24 hours |