TAK-503 for ADHD

No longer recruiting at 82 trial locations

Overseen By Melissa P. DelBello

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Shire

Must not be taking: Sedating antihistamines, Decongestant sympathomimetics

Disqualifiers: PTSD, Bipolar, Substance abuse, others

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

Compensation: Varies

Number of Visits: 73

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term effects of a medication called TAK-503 in children and teenagers with ADHD who have not responded to stimulant treatments. The study consists of two parts: in the first, participants may receive TAK-503 (guanfacine hydrochloride), atomoxetine, or a placebo; in the second, all participants will receive TAK-503. Children and teens aged 6 to 17 diagnosed with ADHD who have not found previous stimulant medications effective might be suitable for this trial. As a Phase 4 trial, this study involves an FDA-approved treatment, aiming to understand its benefits for more patients.

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 is the safety track record for these treatments?

A previous study found atomoxetine effective and generally safe for treating ADHD. However, short-term studies revealed an increased risk of suicidal thoughts in children and teens. Long-term research confirmed its safety for adults. For guanfacine hydrochloride (TAK-503), research shows no major safety concerns for long-term use in adults with ADHD. Studies in children and teens also found that appropriate doses were effective and safe. This trial is in Phase 4, indicating the treatment is already approved and used for another condition, suggesting it is likely safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard ADHD treatments, which typically involve stimulants like methylphenidate and amphetamines, TAK-503 (Guanfacine hydrochloride) offers a non-stimulant option. Researchers are excited because TAK-503 acts on alpha-2 adrenergic receptors, which may help improve attention and reduce hyperactivity without the stimulant-related side effects such as insomnia or appetite suppression. Additionally, TAK-503 is being explored for its potential to offer a more flexible dosing schedule, allowing for personalized treatment adjustments that could better meet individual patient needs.

What evidence suggests that this trial's treatments could be effective for ADHD?

Research has shown that atomoxetine, a treatment in this trial, can help people with ADHD by improving attention and reducing hyperactivity. Studies indicate it leads to moderate symptom improvements after several months. Guanfacine, also known as TAK-503, is another treatment option in this trial and has shown promising results. It significantly reduces ADHD symptoms compared to a placebo. A review of multiple studies found that 59% of patients benefit from guanfacine treatment. This trial evaluates both treatments for their effectiveness in managing ADHD. ^{6 7 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda Development Center Americas

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5069588/

Atomoxetine Increased Effect over Time in Adults ... Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment.

2. eneuro.org eneuro.org/content/12/4/ENEURO.0371-24.2025

Clinical Efficacy of Atomoxetine Hydrochloride Combined ... It is also demonstrated to improve inattention and hyperactivity/impulsivity scores in patients with ADHD (Micoulaud-Franchi et al., 2014).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5304987/

A review of the efficacy of atomoxetine in the treatment of ... Overall, atomoxetine was comparable in efficacy against ADHD symptoms in patients with ADHD with or without a learning or language disorder. Importantly, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0890856724003046

Systematic Review and Meta-Analysis: Effects of ... The analysis showed that medications such as amphetamines, methylphenidate, and atomoxetine improved QoL compared to placebo, with moderate effect sizes.

5. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.159.11.1896

Once-Daily Atomoxetine Treatment for Children and ... Atomoxetine, a new investigational compound, has been shown to be efficacious in children and adults with ADHD when administered twice daily.

6. mayoclinic.org mayoclinic.org/drugs-supplements/atomoxetine-oral-route/description/drg-20066904

Atomoxetine (oral route) - Side effects & dosage Atomoxetine is used to treat attention-deficit hyperactivity disorder (ADHD) in children, teenagers, and adults. ... Safety and efficacy have not ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/021411s035lbl.pdf

Strattera (atomoxetine hydrochloride) capsules label STRATTERA increased the risk of suicidal ideation in short-term studies in children and adolescents with Attention. Deficit/Hyperactivity Disorder (ADHD).

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8863678/

The Mechanism, Clinical Efficacy, Safety, and Dosage ... Atomoxetine is effective and generally well tolerated. ADHD is often accompanied by multiple comorbidities. A series of studies have been published suggesting ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK493234/

Atomoxetine - StatPearls - NCBI Bookshelf - NIH Although atomoxetine is only FDA-approved for treating ADHD, it is sometimes used off-label to treat adult patients with treatment-resistant depression. This ...

10. scielo.isciii.es scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0213-61632013000300005

Safety and tolerability of atomoxetine hydrochloride in a long ... This study demonstrated that atomoxetine exhibited an acceptable safety profile in adults with ADHD during 24 weeks of treatment and during an additional 25 ...