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

574 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will test if centanafadine, a daily extended-release medication, can help children aged 4 to 12 years with ADHD by balancing brain chemicals to improve focus and reduce hyperactivity. Centanafadine is being investigated for the treatment of ADHD.

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.

What data supports the idea that Centanafadine for ADHD is an effective drug?

The available research shows that Centanafadine is effective for treating ADHD in adults. Two phase 2 studies and two phase 3 trials found that Centanafadine, which affects certain brain chemicals, helps reduce ADHD symptoms. These studies were carefully controlled to compare Centanafadine with a placebo, which is a fake treatment used to see if the real drug works better. The results showed that Centanafadine was more effective than the placebo in improving ADHD symptoms. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Centanafadine for ADHD?

Research shows that Centanafadine, which affects brain chemicals like norepinephrine, dopamine, and serotonin, has been tested in adults with ADHD and found to be effective in improving symptoms in phase 2 and phase 3 studies. ^{1 2 3 4 5}

What safety data is available for Centanafadine in treating ADHD?

Safety data for Centanafadine, also known as Centanafadine SR or XR, has been evaluated in multiple studies. Phase 2 and Phase 3 trials have assessed its safety and tolerability in adults with ADHD. These studies were randomized, double-blind, and placebo-controlled, indicating a rigorous evaluation of safety. However, specific adverse events or safety outcomes from these trials are not detailed in the provided abstracts. Additionally, there is no specific mention of Centanafadine in the retrospective analysis of adverse events associated with non-stimulant ADHD medications or in the drug-drug interaction study, suggesting limited post-marketing safety data or interaction data for Centanafadine at this time. ^{1 2 6 7 8}

Is Centanafadine safe for humans?

Centanafadine has been studied in adults with ADHD, and the research suggests it is generally safe, with no major safety concerns reported in the studies. However, as with any medication, monitoring for side effects is important. ^{1 2 6 7 8}

Is the drug Centanafadine a promising treatment for ADHD?

Yes, Centanafadine is a promising drug for treating ADHD. It has shown positive results in multiple studies, including Phase 2 and Phase 3 trials, where it was tested for safety and effectiveness in adults with ADHD. This drug works by affecting certain chemicals in the brain that are linked to attention and behavior. ^{1 2 3 9 10}

How is the drug Centanafadine unique for treating ADHD?

Centanafadine is unique because it works by inhibiting the reuptake of three neurotransmitters (chemical messengers in the brain): norepinephrine, dopamine, and serotonin, which is different from many other ADHD medications that typically target only one or two of these neurotransmitters. ^{1 2 3 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Centanafadine Sustained-Release in Adults With Attention-Deficit Hyperactivity Disorder: Results of Phase 2 Studies. [2022]

2. United States 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. [2022]

3. Ireland 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Morning and Evening Effects of Guanfacine Extended Release Adjunctive to Psychostimulants in Pediatric ADHD. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. [2013]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Clinically Significant Drug-Drug Interactions with Agents for Attention-Deficit/Hyperactivity Disorder. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. [2018]

8. Ireland 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. [2021]

9. United States 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. [2022]