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

NCT ID: NCT04085172

Last Updated: 2025-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 396 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-18
• Study Completion Date: 2025-09-02

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.

Detailed Description

This study will be conducted in two parts Part A and Part B. Part A is a double-blinded, double-dummy, placebo-controlled study with an atomoxetine arm as an active reference to TAK-503. Eligible participants with ADHD will be randomized in a 1:1:1 ratio among TAK-503, atomoxetine, and placebo treatment arms for 18 weeks of double-blinded treatment. At the end of the 18 weeks, participants will roll over to Part B directly as per the study protocol directions for an additional 52 weeks of open-label TAK-503 treatment.

Conditions

Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part A: Guanfacine hydrochloride (TAK-503)

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 Type: EXPERIMENTAL

Guanfacine hydrochloride (TAK-503)

Intervention Type: 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.

Part A: Atomoxetine hydrochloride

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 Type: ACTIVE_COMPARATOR

Atomoxetine hydrochloride

Intervention Type: DRUG

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

Part A: Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 B: Guanfacine hydrochloride (TAK-503)

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 Type: EXPERIMENTAL

Guanfacine hydrochloride (TAK-503)

Intervention Type: 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.

Interventions

Guanfacine hydrochloride (TAK-503)

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.

Intervention Type: DRUG

Atomoxetine hydrochloride

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

Intervention Type: DRUG

Placebo

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.

Intervention Type: OTHER

Other Intervention Names

Intuniv; SPD503

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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):

1. Post-traumatic stress disorder (PTSD)

2. Bipolar illness, psychosis, or family history in either biological parent

3. Pervasive developmental disorder

4. Obsessive-compulsive disorder (OCD)

5. Psychosis/schizophrenia

6. 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.
• Participant has a known history or presence of: malignancy (except nonmelanoma skin cancer), pregnancy, and/or a developmental delay or abnormality associated with growth or sexual maturation delays that are not related to ADHD.
• Children aged 6 to 12 years with a body weight less than (<) 25.0 kg or adolescents aged > = 13 years with a body weight < 34.0 kg at screening (Visit 1A) or baseline (Visit 2A).
• Participant is significantly overweight based on the Centers for Disease Control (CDC) BMI-for-age sex-specific charts at screening (Visit 1A) or baseline (Visit 2A). For this study, significantly overweight will be defined as a BMI that is greater than the 95th percentile.
• Participant has a known history or presence of: structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g. clinically significant heart block or QT interval prolongation), bradycardia, or exercise-related cardiac events including syncope and presyncope.
• Participant has clinically significant electrocardiogram (ECG) findings, as judged by the investigator, at baseline (Visit 2A).
• Participant has orthostatic hypotension* or a known history of hypertension. (*Orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 millimeter of mercury (mm Hg) or diastolic blood pressure of 10 mm Hg within 3 minutes of standing from supine.)
• Participant has a known family history of sudden cardiac death or ventricular arrhythmia.
• Participant is currently using any medication that violates protocol-specified washout criteria at baseline (Visit 2A), including any ADHD medication or other prohibited medications such as herbal supplements, medications that affect BP or heart rate (HR) or medications that have central nervous system (CNS) effects or affect cognitive performance, such as sedating antihistamines and decongestant sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use of sedating medications (i.e., antihistamines).
• Participant has a medical condition except ADHD that requires treatment with any medication that affects the CNS.
• Participant is female and pregnant or currently lactating.
• Participant has taken another investigational product or participated in a clinical study within 30 days before screening (Visit 1A).
• Participant does not tolerate or has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, atomoxetine, or any TAK-503 or atomoxetine drug product component.
• Participant has a history of a seizure disorder (except for a single childhood febrile seizure episode that occurred before the age of 3 years)
• Participant is well-controlled on his/her current ADHD medication with acceptable tolerability, and the parent/treating physician does not object to the current medication.
• Participant has alanine transaminase (ALT) greater than (>) 2*upper limit of normal (ULN) or aspartate aminotransferase (AST) >2*ULN or bilirubin >1.5*ULN at screening.

Study Part B:

• Participant failed screening, voluntarily withdrew, or was discontinued from Study Part A for protocol nonadherence, participant noncompliance, or TEAE or SAE.
• Participant had any clinically significant TEAE during Study Part A that, as judged by the investigator, would preclude exposure to TAK-503.
• Participant has a history of alcohol or other substance abuse or dependence, as defined by DSM-5 (with the exception of nicotine) within the last 6 months.
• Participant currently uses any of the prohibited medication or other medications, including herbal supplements, that affect BP or HR or that have CNS effects or affect cognitive performance, such as sedating antihistamines and decongestant sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use of sedating medications (i.e. antihistamines) in violation of the protocol-specified washout criteria at baseline.
• Participant has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, or any components found in TAK-503.
• Participant has taken any IMP except placebo in Study Part A within the 30 days before baseline of Study Part B (Visit 2B).
• Participant is significantly overweight based on the CDC BMI-for-age sex-specific charts at screening. Significantly overweight is defined as a BMI > 95th percentile.
• Participant is a child aged 6 to 12 years with a body weight of < 25.0 kg or an adolescent aged > = 13 years with a body weight of < 34.0 kg at screening (Visit 1B)
• Participant has any condition or illness including clinically significant abnormal laboratory values at screening which as judged by the investigator would represent an inappropriate risk to the participant and/or confound the interpretation of study results.
• Participant is currently considered a suicide risk as judged by the investigator, has previously made a suicide attempt, has a history of, or is currently demonstrating active suicidal ideation. Participants with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator.
• Participant has clinically significant ECG findings, as judged by the investigator, at baseline (Visit 2B).
• Participant has a known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g. clinically significant heart block), exercise-related cardiac events including syncope and presyncope, or clinically significant bradycardia.
• Participant has orthostatic hypotension or a known history of hypertension. (*Orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of 10 mm Hg within 3 minutes of standing from supine).
• Participant has a history of a seizure disorder (except for a single childhood febrile seizure episode that occurred before the age of 3 years) or the presence of a serious tic disorder including Tourette's syndrome.
• Participant has a medical condition except ADHD, which requires treatment with any medication that affects the CNS.
• Participant has ALT >2*ULN or AST >2*ULN or bilirubin >1.5*ULN at screening.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda Development Center Americas, Inc.

INDUSTRY

Sponsor Role: collaborator

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda Development Center Americas

Locations

Harmonex Neuroscience Research

Dothan, Alabama, United States

Advanced Research Center, Inc.

Anaheim, California, United States

Sun Valley Research Center, Inc.

Imperial, California, United States

Alliance Research

Long Beach, California, United States

PCSD Feighner Research

San Diego, California, United States

Homestead Medical Research

Homestead, Florida, United States

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, United States

Care Research Center, Inc.

Miami, Florida, United States

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States

AMR Conventions Research, Ltd

Naperville, Illinois, United States

Collective Medical Research LLC

Prairie Village, Kansas, United States

Qualmedica Research, LLC

Bowling Green, Kentucky, United States

Qualmedica Research, LLC

Owensboro, Kentucky, United States

Alivation Research, LLC

Lincoln, Nebraska, United States

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, United States

Family Psychiatry of The Woodlands

The Woodlands, Texas, United States

Clinical Research Partners, LLC

Petersburg, Virginia, United States

LKH-Klinikum Graz

Graz, , Austria

Medizinische Universtität Wien

Vienna, , Austria

UZ Brussel

Brussels, , Belgium

UPC KU Leuven Afdeling Kinderpsychiatrie ADHD-raadpleging

Leuven, , Belgium

Foyer Saint Francois

Namur, , Belgium

Zentralinstitut fuer Seelische Gesundheit

Mannheim, Baden-Wurttemberg, Germany

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, Germany

Rheinhessen-Fachklinik Mainz

Mainz, Rhineland-Palatinate, Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

EB FlevoResearch

Almere Stad, , Netherlands

EB UtrechtResearch

Utrecht, , Netherlands

Hospital de Cascais - Dr. José de Almeida

Alcabideche, , Portugal

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

Braga, , Portugal

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

Covilha, , Portugal

Hospital da Senhora da Oliveira Guimarães

Guimarães, , Portugal

Hospital CUF Descobertas

Lisbon, , Portugal

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

Porto, , Portugal

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Clinica Dr. Quintero

Madrid, , Spain

Hospital Infanta Leonor

Madrid, , Spain

Hospital Universitario Fundacion Alcorcon

Madrid, , Spain

Complejo Hospitalario de Palencia

Palencia, , Spain

Corporacio Sanitaria Parc Tauli

Sabadell, , Spain

Instituto Valenciano de Neurología Pediátrica (INVANEP)

Valencia, , Spain

Barnneuropsykiatriska enheten, Sahlgrenska University hospital

Gothenburg, , Sweden

Regionhälsan

Mölnlycke, , Sweden

PRIMA Barn- och Vuxenpsykiatri AB

Norsborg, , Sweden

Tayside Children Hospital

Dundee, , United Kingdom

Lister Hospital

Stevenage, , United Kingdom

Countries

United States; Austria; Belgium; Germany; Netherlands; Portugal; Spain; Sweden; United Kingdom

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b600a4db2bf003ab48b68

To obtain more information on the study, click here/on this link

Other Identifiers

2018-000821-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TAK-503-401

Identifier Type: OTHER

Identifier Source: secondary_id

2022-502630-71-00

Identifier Type: CTIS

Identifier Source: secondary_id

SPD503-401

Identifier Type: -

Identifier Source: org_study_id