TAK-503 for ADHD

Recruiting at 75 trial locations

Overseen By Melissa P. DelBello

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Shire

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

Compensation: Varies

Number of Visits: 73

288 Participants Needed

Trial Summary

What is the purpose of this trial?

The main aim of this study is learn more about long-term TAK-503 treatment in children and teenagers with ADHD for whom earlier stimulant treatment did not work. The study has two parts (A and B). In Part A, participants will take tablets of TAK-503, atomoxetine or placebo and in Part B TAK-503 tablets.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any medications that affect the central nervous system (CNS) or those that affect blood pressure or heart rate. There is a specific 'washout' period (time without taking certain medications) for these medications before starting the trial.

What data supports the effectiveness of the drug TAK-503 for ADHD?

Research shows that guanfacine extended-release, a component of TAK-503, is effective in reducing ADHD symptoms in both children and adults. Studies have demonstrated its safety and efficacy in improving attention and behavior compared to a placebo. ^{1 2 3 4 5}

Is TAK-503 (Atomoxetine hydrochloride) safe for humans?

Atomoxetine hydrochloride, used for ADHD, has been studied for safety in children and adolescents. Clinical trials show it is generally safe, but like any medication, it can have side effects, especially in overdose situations. ^{6 7 8 9 10}

How is TAK-503 different from other ADHD drugs?

TAK-503 combines atomoxetine hydrochloride, a non-stimulant that increases norepinephrine (a brain chemical) levels, with guanfacine hydrochloride, which targets specific receptors in the brain to help improve attention and reduce hyperactivity. This combination offers a unique approach by using two non-stimulant components, potentially providing an alternative for those who do not respond well to stimulant medications. ^{1 3 4 5 11}

Research Team

Study Director

Principal Investigator

Takeda Development Center Americas

Eligibility Criteria

This trial is for children and teenagers aged 6 to 17 with ADHD who haven't responded well to stimulant therapy. They must have an intellectual function appropriate for their age, a certain score on the ADHD rating scale, and normal blood pressure. Those with heart issues, allergies to study drugs, or other significant health problems are excluded.

Inclusion Criteria

Your score on the ADHD-RS-5 test is 28 or higher at the start of the study.

Study Part B: Female participants of child-bearing potential must have a negative serum β-hCG pregnancy test if a screening visit is conducted and/or a negative urine pregnancy test at baseline and agree to comply with any applicable contraceptive requirements of the protocol.

I am between 6 and 17 years old.

Exclusion Criteria

You have experienced physical, sexual, or emotional abuse.

Study Part A: Participant has any condition or illness including any clinically significant abnormal laboratory value at screening or baseline that, as judged by the investigator, would be an inappropriate risk to the participant and/or could confound the interpretation of study results.

Study Part A: Participant is significantly overweight based on the CDC BMI-for-age sex-specific charts at screening or baseline.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive TAK-503, atomoxetine, or placebo in a double-blind, placebo-controlled setup for 18 weeks

18 weeks

Baseline, Week 10, Week 18

Treatment Part B

Participants receive open-label TAK-503 for 52 weeks

52 weeks

Baseline, Week 10, Week 23, Week 36, Week 49

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Week 53

Treatment Details

Interventions

• Atomoxetine hydrochloride
• Guanfacine hydrochloride (TAK-503)
• Placebo

Trial Overview The trial tests TAK-503 against atomoxetine and placebo in kids and teens with ADHD over two parts. In Part A, participants randomly receive one of the three treatments; those on placebo then get TAK-503 in Part B while others continue on TAK-503.

Participant Groups

Group I: Part B: Guanfacine hydrochloride (TAK-503) Experimental Treatment 1 Intervention

Participants from Part A will roll over into Part B directly after 18 weeks and will receive TAK-503 at an initial dose of 1 mg, and up titrated with weekly incremental dose of 1 mg until an optimal dose is reached. Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablet QD for 52 weeks of Part B.

Group II: Part A: Guanfacine hydrochloride (TAK-503) Experimental Treatment 1 Intervention

Participants randomized to TAK-503 will receive initial dose of 1 milligram (mg), and up titrated with weekly incremental dose of 1 mg until an optimal dose is reached. Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablet once daily (QD) for 18 weeks.

Group III: Part A: Atomoxetine hydrochloride Active Control 1 Intervention

Participants who weigh less than (\<) 70 kilograms (kg) at baseline will receive Atomoxetine hydrochloride capsule orally at an initial dose of 0.5 milligram per kilogram (mg/kg) which may be increased to the target dose of 1.2 mg/kg oral capsule QD during the treatment of 18 weeks. Permitted doses of Atomoxetine hydrochloride capsule will be 10, 18, 25, 40, 60, and 80 mg QD. Participants who weigh \>= 70 kg at baseline will receive Atomoxetine hydrochloride at an initial dose of 40 mg oral capsule QD which may be increased to 80 mg and then to 100 mg for 18 weeks. The total dose for participants who weigh \>= 70 kg at baseline will not exceed 100 mg.

Group IV: Part A: Placebo Placebo Group 1 Intervention

Participants aged 6 to 12 years will receive a dose of 1 to 4 mg tablet of placebo matched to TAK-503 and aged 13 to 17 years will receive a dose of 5 to 7 mg tablets of placebo matched to TAK-503 orally QD for 18 weeks. Participants who weigh \< 70 kg at baseline will receive placebo matched to Atomoxetine hydrochloride oral capsule at an initial dose of 0.5 mg/kg which may be increased to the target dose of 1.2 mg/kg QD oral capsule during the treatment of 18 weeks. Permitted doses of placebo matched to Atomoxetine hydrochloride will be 10, 18, 25, 40, 60, and 80 mg QD and participants who weigh \>= 70 kg will receive placebo matched to Atomoxetine hydrochloride at an initial dose of 40 mg QD capsule orally which may be increased to 80 mg and then to 100 mg.

Who Is Running the Clinical Trial?

Shire

Lead Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Findings from Research

In a long-term study of 191 adults with ADHD, guanfacine extended-release (GXR) was found to be safe, with most treatment-emergent adverse events (TEAEs) being mild to moderate, and only 19.9% of patients discontinuing due to TEAEs.

Significant improvements in ADHD symptoms, quality of life, and executive functioning were observed after 50 weeks of GXR treatment, indicating its efficacy as a long-term management option for adults with ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study. Iwanami, A., Saito, K., Fujiwara, M., et al.[2022]

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]

Atomoxetine is a safe and effective alternative treatment for ADHD in children and adolescents, showing significant reductions in ADHD symptoms in clinical trials with a mean dose of 1.5 mg/kg/day.

The drug has a favorable safety profile, with only 2.8% of participants discontinuing due to adverse effects, which primarily included gastrointestinal symptoms and decreased appetite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents]. Purper-Ouakil, D., Fourneret, P., Wohl, M., et al.[2020]

In a study of 297 children and adolescents with ADHD, atomoxetine was found to be significantly more effective than placebo in reducing ADHD symptoms and improving social and family functioning over an 8-week period.

The study demonstrated a graded dose-response, with doses of 1.2 mg/kg/day and 1.8 mg/kg/day showing similar efficacy, suggesting that 1.2 mg/kg/day may be the optimal starting dose for treatment, while adverse events were minimal, with discontinuations due to side effects being less than 5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Michelson, D., Faries, D., Wernicke, J., et al.[2022]

In a study of 64 children who experienced atomoxetine exposure, 21 reported adverse drug reactions such as agitation, elevated blood pressure, and nausea, but these reactions did not correlate with the dosage taken.

Despite some patients experiencing hypertension after overdose, all patients were discharged from healthcare facilities without lasting effects, indicating that while atomoxetine overdose can lead to adverse reactions, serious long-term consequences are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children and adolescent exposures to atomoxetine hydrochloride reported to a poison control center. Stojanovski, SD., Robinson, RF., Baker, SD., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness research using matching-adjusted indirect comparison: an application to treatment with guanfacine extended release or atomoxetine in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of extended-release guanfacine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, controlled, phase III trial. [2022]

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

Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. [2022]

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. France pubmed.ncbi.nlm.nih.gov

[Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents]. [2020]

7. Spain pubmed.ncbi.nlm.nih.gov

[Current evidence about atomoxetine. A therapeutic alternative for the treatment of attention deficit hyperactivity disorder]. [2015]

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

Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Children and adolescent exposures to atomoxetine hydrochloride reported to a poison control center. [2019]

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

Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression. [2022]

11. England pubmed.ncbi.nlm.nih.gov

A retrospective medical chart review of clinical outcomes in children and adolescents with attention-deficit/hyperactivity disorder treated with guanfacine extended-release in routine Canadian clinical practice. [2021]