A Study of TAK-503 in Children and Teenagers With Attention Deficit Hyperactivity Disorder (ADHD)

NCT04085172 | Completed Phase 4 Results FDA Drug

• 4 other identifiers: SPD503-4012018-000821-29TAK-503-4012022-502630-71-00
• Study Type: interventional
• Target: 396
• Locations: 9 countries
• Sites: 50

Brief Summary

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.

Conditions

Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (3)

• Part A: Change From Baseline in the Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI) Task at Week 18

  The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circles for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in milliseconds (msec) ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.

  At Baseline, Week 18

• Part A: Change From Baseline in the CANTAB RTI Task at Week 49

  The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.

  At Baseline, Week 49

• Part B: Change From Baseline in the CANTAB RTI Task at Week 49

  The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.

  At Baseline, Week 49

Secondary Outcomes (40)

• Part A: Change From Baseline in the Rapid Visual Information Processing (RVP) Task of the CANTAB: Mean Response Latency

  Baseline, Weeks 18 and 49

• Part B: Change From Baseline in the RVP Task of the CANTAB: Mean Response Latency

  Baseline, Week 49

• Part A: Change From Baseline in the RVP Task of the CANTAB: A'

  Baseline, Weeks 18 and 49

• Part B: Change From Baseline in the RVP Task of the CANTAB: A'

  Baseline, Week 49

• Part A: Change From Baseline in the RVP Task of the CANTAB: Probability of Hit

  Baseline, Weeks 18 and 49

Study Arms (4)

Part A: Guanfacine hydrochloride (TAK-503)

EXPERIMENTAL

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.

Drug: Guanfacine hydrochloride (TAK-503)

Part A: Atomoxetine hydrochloride

ACTIVE COMPARATOR

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.

Drug: Atomoxetine hydrochloride

Part A: Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Part B: Guanfacine hydrochloride (TAK-503)

EXPERIMENTAL

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.

Drug: Guanfacine hydrochloride (TAK-503)

Interventions

Atomoxetine hydrochloride DRUG

Participants will receive Atomoxetine hydrochloride oral capsule once daily for 18 weeks in Part A.

Part A: Atomoxetine hydrochloride

Guanfacine hydrochloride (TAK-503) DRUG

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 tablets once daily for 18 weeks in Part A or 52 weeks in Part B.

Also known as: Intuniv, SPD503

Part A: Guanfacine hydrochloride (TAK-503); Part B: Guanfacine hydrochloride (TAK-503)

Placebo OTHER

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 placebo matched to TAK 503 oral tablets once daily for 18 weeks and placebo matched to atomoxetine hydrochloride oral capsules at once daily for 18 weeks in Part A.

Part A: Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Study Part A:
• Participant is a male or female aged 6 to 17 years inclusive at the time of consent/assent.
• Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation using the Kiddie-Schedule for Affective Disorders-Present and Lifetime Version (K-SADS-PL) by a trained child and adolescent psychiatrist at screening (Visit 1A).
• Participant for whom prior stimulant therapy is not suitable, not tolerated, or shown to be ineffective as determined by investigator clinical assessment and review of the Prior Stimulant Medication Questionnaire (PSMQ) administered during screening (Visit 1A).
• Participant has an ADHD-RS-5 total score greater than or equal to (\> =) 28 at baseline (Visit 2A).
• Participant has a baseline (Visit 2A) CGI-S score \> = 4.
• Participant who is a female of childbearing potential (FOCP) and postmenarchal must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening (Visit 1A) and a negative urine pregnancy test at baseline (Visit 2A), be nonlactating, and agree to comply with any applicable contraceptive requirements described in the protocol. Female of child bearing potential is defined as any female participant who is at least aged 9 years or younger than 9 years and postmenarchal.
• Participants parent or legally authorized representative (LAR) must provide signature of informed consent. Documentation of assent (if applicable) must be provided by the participant indicating that the participant is aware of the investigational nature of the study and the required procedures and restrictions in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6\[R2\] and applicable regulations, before completing any study-related procedures.
• Participant and parent/LAR are willing and able to comply with all the testing and requirements defined in this protocol, including oversight of morning dosing. Specifically, the parent/LAR must be available for the duration of the study to administer the investigational medicinal product (IMP) dose each morning when the participant awakens.
• Participant has supine and standing blood pressure (BP) measurements less than the 95th percentile for age, sex, and height at both screening (Visit 1A) and baseline (Visit 2A).
• Participant is functioning at an age-appropriate level intellectually, as judged by the investigator.
• Participant is able to swallow intact tablets and capsules.
• 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. An FOCP is defined as any female participant who is at least aged 9 years or younger than 9 years and postmenarchal.
• Participant has a supine and standing BP measurement less than the 95th percentile for age, sex, and height.

You may not qualify if:

• Study Part A:
• Participant has a current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder (except oppositional defiant disorder), including but not limited to any of the following comorbid Axis I and Axis II disorders (the K-SADS-PL should be reviewed to confirm diagnosis, if necessary):
• Post-traumatic stress disorder (PTSD)
• Bipolar illness, psychosis, or family history in either biological parent
• Pervasive developmental disorder
• Obsessive-compulsive disorder (OCD)
• Psychosis/schizophrenia
• Serious tic disorder or a family history of Tourette's disorder
• Participant is currently considered to be a suicide risk by the investigator; has made a previous suicide attempt; has a history of, or currently demonstrating, active suicidal ideation.
• Participant has a substance abuse disorder as defined by DSM-5 criteria or has been suspected of a substance abuse or dependence disorder (except nicotine) within the past 6 months.
• Participant has a clinically important abnormality on the urine drug and alcohol screen (except for the participants current ADHD stimulant, if applicable) at screening (Visit 1A).
• Participant has been physically, sexually, and/or emotionally abused.
• Participant has any other disorder that as judged by the investigator could contraindicate TAK-503 or confound the results of the safety and efficacy assessments.
• Participant has any condition or illness including any clinically significant abnormal laboratory value at screening (Visit 1A) or, if the laboratory test was repeated, at baseline (Visit 2A) that, as judged by the investigator, would be an inappropriate risk to the participant and/or could confound the interpretation of study results.
• Participant has current abnormal thyroid function, defined as abnormal thyroid-stimulating hormone and thyroxine at screening (Visit 1A). Treatment with a stable dose of thyroid medication for \> = 3 months before screening will be permitted.

Sponsors & Collaborators

• Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (50)

Harmonex Neuroscience Research

Dothan, Alabama, 36303, United States

Location

Advanced Research Center, Inc.

Anaheim, California, 92805, United States

Location

Sun Valley Research Center, Inc.

Imperial, California, 92251, United States

Location

Alliance Research

Long Beach, California, 90807, United States

Location

PCSD Feighner Research

San Diego, California, 92108, United States

Location

Homestead Medical Research

Homestead, Florida, 33030, United States

Location

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

Location

Care Research Center, Inc.

Miami, Florida, 33130, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

Location

AMR Conventions Research, Ltd

Naperville, Illinois, 60563, United States

Location

Collective Medical Research LLC

Prairie Village, Kansas, 66208, United States

Location

Qualmedica Research, LLC

Bowling Green, Kentucky, 42101, United States

Location

Qualmedica Research, LLC

Owensboro, Kentucky, 42301, United States

Location

Alivation Research, LLC

Lincoln, Nebraska, 68526, United States

Location

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, 89128, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

Family Psychiatry of The Woodlands

The Woodlands, Texas, 77381, United States

Location

Clinical Research Partners, LLC

Petersburg, Virginia, 23805, United States

Location

LKH-Klinikum Graz

Graz, 8036, Austria

Location

Medizinische Universtität Wien

Vienna, 1090, Austria

Location

UZ Brussel

Brussels, 1090, Belgium

Location

UPC KU Leuven Afdeling Kinderpsychiatrie ADHD-raadpleging

Leuven, 3000, Belgium

Location

Foyer Saint Francois

Namur, 5000, Belgium

Location

Zentralinstitut fuer Seelische Gesundheit

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Rheinhessen-Fachklinik Mainz

Mainz, Rhineland-Palatinate, 55122, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79104, Germany

Location

EB FlevoResearch

Almere Stad, 1311RL, Netherlands

Location

EB UtrechtResearch

Utrecht, 3562KX, Netherlands

Location

Hospital de Cascais - Dr. José de Almeida

Alcabideche, 2755-009, Portugal

Location

Centro Clinico Academico 2CA Associacao Braga, Hospital de Braga Piso 1, Ala E

Braga, 4710-243, Portugal

Location

Centro Hospitalar Universitario Cova da Beira, E.P.E

Covilha, 6200-502, Portugal

Location

Hospital da Senhora da Oliveira Guimarães

Guimarães, 4835-044, Portugal

Location

Hospital CUF Descobertas

Lisbon, 1998-018, Portugal

Location

Centro Materno Infantil do Norte (CMIN) Centro Hospitalar Universitario do Porto

Porto, 4099-001, Portugal

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31080, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Clinica Dr. Quintero

Madrid, 28002, Spain

Location

Hospital Infanta Leonor

Madrid, 28031, Spain

Location

Hospital Universitario Fundacion Alcorcon

Madrid, 28922, Spain

Location

Complejo Hospitalario de Palencia

Palencia, 34005, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, 8208, Spain

Location

Instituto Valenciano de Neurología Pediátrica (INVANEP)

Valencia, 46010, Spain

Location

Barnneuropsykiatriska enheten, Sahlgrenska University hospital

Gothenburg, 41118, Sweden

Location

Regionhälsan

Mölnlycke, 43530, Sweden

Location

PRIMA Barn- och Vuxenpsykiatri AB

Norsborg, 145 67, Sweden

Location

Tayside Children Hospital

Dundee, DD1 9SY, United Kingdom

Location

Lister Hospital

Stevenage, SG1 4AB, United Kingdom

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
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MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Guanfacine; Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Propylamines; Amines

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda Development Center Americas

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study contains two parts (Part A and Part B), where Part A will be double blind, double dummy parts of the study followed by Part B as an open label part of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 11, 2019
• Study Start: September 18, 2019
• Primary Completion: September 2, 2025
• Study Completion: September 2, 2025
• Last Updated: April 13, 2026
• Results First Posted: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

AU (2); US (20); DE (4); BE (3); NL (2); ES (8); GB (2); PT (6); SE (3)