Centanafadine for ADHD

Overseen By Otsuka Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Disqualifiers: Tourette's, Anxiety, Panic, Conduct, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a medication called centanafadine for treating ADHD in children. It tests both high and low doses of the medication against a placebo (a pill with no active drug) to assess how well it manages ADHD symptoms. Children diagnosed with ADHD who experience significant symptoms affecting their daily life might be suitable candidates for this study. Participants will undergo a screening period, receive treatment, and then have follow-up evaluations. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have started, changed, or stopped psychological interventions for ADHD within 30 days before the screening, you may not be eligible.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that centanafadine is likely to be safe for children with ADHD?

Research has shown that centanafadine is generally safe for treating ADHD. One study found that adults taking 400 mg per day of centanafadine experienced safe and effective results over a long period. Another study demonstrated that adolescents tolerated centanafadine well, with doses proving both safe and effective.

For children aged 6 to 12, centanafadine at doses resulting in similar blood levels as in adults also improved ADHD symptoms, indicating good tolerance in children. Overall, these studies suggest that centanafadine is generally safe, with few side effects reported. However, it is important to consult a healthcare provider to discuss potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ADHD?

Centanafadine is unique because it targets multiple neurotransmitters—dopamine, norepinephrine, and serotonin—simultaneously, which sets it apart from most current ADHD treatments that primarily focus on just one neurotransmitter. This multi-target approach could potentially offer a more comprehensive improvement in managing ADHD symptoms. Researchers are particularly excited about its weight-based dosing, which allows for more personalized treatment, especially in young children. Unlike traditional stimulant medications, Centanafadine's novel mechanism of action might also carry a different side effect profile, offering a promising alternative for those who experience undesirable effects with current options.

What evidence suggests that centanafadine might be an effective treatment for ADHD?

Research shows that centanafadine can help treat ADHD. In this trial, participants will receive either a weight-based high dose or low dose of centanafadine, or a matching placebo. One study found that a daily dose similar to 400 mg for adults improved ADHD symptoms in children aged 6 to 12. Other studies have shown that centanafadine is safe and effective for teenagers. It was well tolerated in these age groups, with positive results in managing symptoms. This suggests that centanafadine could be a promising treatment option for children with ADHD. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for boys and girls aged 4 to 12 with ADHD, confirmed by specific diagnostic criteria. They must have a certain level of symptom severity and not be undergoing recent or upcoming changes in psychological treatments. Children with severe other mental health conditions or at risk of suicide are excluded.

Inclusion Criteria

A score of 4 or higher on the CGI-S-ADHD at baseline.

You have a score of 4 or higher on the CGI-S-ADHD at baseline.

You have been diagnosed with ADHD using DSM-5 criteria and confirmed through the MINI-KID assessment.

Exclusion Criteria

Comorbid diagnosis of: Tourette's Disorder, Generalized Anxiety Disorder that is severe enough to interfere with trial procedures, Panic Disorder, Conduct Disorder, Psychosis, Post-traumatic Stress Disorder, Bipolar Disorder, Autism Spectrum Disorder, Oppositional Defiant Disorder that is severe enough to interfere with trial conduct (allowed if it is not the primary focus of treatment), Obsessive-Compulsive Disorder that is severe enough to interfere with trial conduct (allowed if it is not the primary focus of treatment), or MDD with current major depressive episode.

BMI ≥ 40 kg/m2 or ≤ 5th percentile for age and gender based on US CDC criteria.

Has initiated, changed, or discontinued receiving psychological interventions for ADHD within the 30 days before the screening visit, or is anticipated to start new treatment during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either centanafadine QD XR or placebo in a double-blind manner

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Centanafadine
• Placebo

Trial Overview The trial tests the effectiveness and safety of centanafadine capsules compared to placebo in treating children's ADHD symptoms. It includes a screening period, a double-blind treatment phase where neither doctors nor patients know who gets the real medicine, and follow-up.

How Is the Trial Designed?

Group I: Weight Based Low Dose Centanafadine Capsules Experimental Treatment 1 Intervention

Cohort 1, (6 to 12 years of age) Low dose - weight-based dosing

Group II: Weight Based High Dose Centanafadine Capsules Experimental Treatment 1 Intervention

Cohort 1, (6 to 12 years of age) Cohort 2, (4 to 5 years of age) High dose - weight-based dosing

Group III: Matching Placebo Placebo Group 1 Intervention

Cohort 1 and Cohort 2 Children (4 to 12 years of age, inclusive) to receive Placebo capsules will be matching in size and color.

Who Is Running the Clinical Trial?

Otsuka Pharmaceutical Development & Commercialization, Inc.

Lead Sponsor

Trials

271

Recruited

170,000+

John Kraus

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Medical Officer since 2023

MD, PhD

Tarek Rabah

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

Published Research Related to This Trial

In a 2-year open-label study involving participants aged 6-17 with ADHD, extended-release guanfacine (GXR) demonstrated long-term safety and efficacy, with most adverse events being mild to moderate.

Significant improvements in ADHD symptoms were observed as early as the first month and continued throughout the 24-month treatment period, supporting GXR as a viable monotherapy for ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Sallee, FR., Lyne, A., Wigal, T., et al.[2013]

In a Phase 3 trial involving 297 adolescents with ADHD, the 400 mg/day dose of SPN-812 showed a statistically significant improvement in ADHD symptoms compared to placebo, while the 600 mg/day dose did not demonstrate superiority, likely due to a high placebo response.

SPN-812 was well tolerated across both doses, with a low discontinuation rate of less than 5% due to adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 3 Placebo-Controlled Trial of Once-Daily 400-mg and 600-mg SPN-812 (Viloxazine Extended-Release) in Adolescents with ADHD. Nasser, A., Liranso, T., Adewole, T., et al.[2022]

Polypharmacy in ADHD treatment can lead to significant drug-drug interactions (DDIs), which may increase the risk of adverse effects, particularly with agents like dextroamphetamine and atomoxetine, where CYP2D6 inhibitors can raise amphetamine levels.

Guanfacine and methylphenidate (MPH) are notably affected by CYP3A4 and carbamazepine, respectively, indicating that clinicians need to adjust dosages based on the presence of these inducers or inhibitors to avoid potential safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically Significant Drug-Drug Interactions with Agents for Attention-Deficit/Hyperactivity Disorder. Schoretsanitis, G., de Leon, J., Eap, CB., et al.[2020]

In a phase 3 safety study of guanfacine extended release (GXR) involving 215 children and adolescents with ADHD, the treatment was well tolerated, with 82.7% experiencing some treatment-emergent adverse events, primarily somnolence and headache.

GXR significantly reduced ADHD symptoms over the 2-year study, with a mean decrease of 19.8 points in the ADHD-RS-IV total score, indicating its efficacy in managing ADHD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. Huss, M., Dirks, B., Gu, J., et al.[2018]

A study analyzing adverse events from nonstimulant ADHD medications (atomoxetine, clonidine, and guanfacine) found that common side effects include ineffectiveness (up to 14.15%), fatigue (8.93%), and somnolence (up to 10.16%).

Suicidal ideation was reported among users of all three medications, highlighting the importance of monitoring and educating patients about potential serious side effects, even though they occur less frequently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of adverse events associated with non-stimulant ADHD medications reported to the united states food and drug administration. Pang, L., Sareen, R.[2021]

In a study involving 1397 pediatric patients with ADHD, early response to treatment with SPN-812 was found to be a strong predictor of long-term efficacy, with a 75% positive predictive power after just two weeks.

The most significant indicators of treatment success were changes in ADHD Rating Scale-5 scores and Clinical Global Impressions-Improvement scores, highlighting the importance of monitoring early treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early response to SPN-812 (viloxazine extended-release) can predict efficacy outcome in pediatric subjects with ADHD: a machine learning post-hoc analysis of four randomized clinical trials. Faraone, SV., Gomeni, R., Hull, JT., et al.[2021]

In a study of 461 children and adolescents with ADHD, adjunctive guanfacine extended release (GXR) significantly improved ADHD symptoms in both morning and evening assessments compared to placebo.

Most side effects from GXR were mild or moderate, indicating that it is a safe option for enhancing the effectiveness of existing psychostimulant treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morning and Evening Effects of Guanfacine Extended Release Adjunctive to Psychostimulants in Pediatric ADHD. Wilens, TE., McBurnett, K., Turnbow, J., et al.[2018]

In a long-term study of 240 children aged 6-17 with ADHD, guanfacine extended release (GXR) was found to be generally safe and effective over a treatment period of up to 2 years, with significant improvements in ADHD symptoms as measured by the ADHD Rating Scale.

The most common side effects included somnolence (30.4%) and headache (26.3%), but these were mostly transient, and serious cardiovascular issues were rare, indicating a favorable safety profile for GXR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. Biederman, J., Melmed, RD., Patel, A., et al.[2022]

Centanafadine sustained-release (SR) significantly reduced ADHD symptoms in adults, with a mean decrease of 21.41 points on the ADHD Rating Scale-IV after 4 weeks of treatment in a phase 2a study with 41 participants.

The phase 2b study with 85 participants showed that centanafadine-SR was effective compared to placebo, with improvements seen as early as week 1, and was generally well tolerated at doses up to 400 mg, with only mild to moderate side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Centanafadine Sustained-Release in Adults With Attention-Deficit Hyperactivity Disorder: Results of Phase 2 Studies. Wigal, SB., Wigal, T., Hobart, M., et al.[2022]

Centanafadine, a medication that inhibits the reuptake of norepinephrine, dopamine, and serotonin, has shown significant efficacy in reducing ADHD symptoms in adults, with notable improvements in the Adult ADHD Investigator Symptom Rating Scale after 42 days of treatment.

The studies demonstrated a low overall rate of treatment-emergent adverse events, indicating that centanafadine is generally safe, with only a slight increase in adverse events at higher doses and low incidences of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials. Adler, LA., Adams, J., Madera-McDonough, J., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0890856725003272

Centanafadine for Attention-Deficit/Hyperactivity Disorder ... Conclusion. Centanafadine 328.8 mg was efficacious for ADHD treatment in adolescents. Both doses were generally safe and well tolerated.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03605836

NCT03605836 | A Trial to Evaluate the Efficacy, Safety, and ... A Trial to Evaluate the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/​Hyperactivity Disorder.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12379780/

52-Week Open-Label Safety and Tolerability Study of ... Results from this trial demonstrate that CTN SR 400 mg is safe and effective for long-term treatment of adults with ADHD. Key Words: ADHD, ...

4. publications.aap.org publications.aap.org/pediatricsopenscience/article/1/3/1/202430/Efficacy-and-Safety-of-Centanafadine-for-ADHD

Efficacy and Safety of Centanafadine for ADHD Treatment ... Once-daily doses of CTN resulting in plasma levels equivalent to the 400-mg daily adult dose improved ADHD symptoms in children aged 6 to 12 ...

5. jaacap.org jaacap.org/article/S0890-8567(25)00327-2/pdf

Centanafadine for Attention-Deficit/Hyperactivity Disorder ... Conclusion: Centanafadine 328.8 mg was efficacious for ADHD treatment in adolescents. Both doses were generally safe and well tolerated. Clinical Trial ...

6. en.wikipedia.org en.wikipedia.org/wiki/Centanafadine

Centanafadine It was developed as a treatment for attention-deficit hyperactivity disorder (ADHD) and inhibits the reuptake of norepinephrine, dopamine, and serotonin with an ...