A Phase 4, Multicenter, 2-part Study Composed of a 1-Year Randomized, Double-blind, Parallel-group, Placebo-controlled, Active-comparator, Dose-optimization Evaluation followed by a 1-Year Open-label Evaluation to Assess the Safety and Efficacy of Guanfacine Hydrochloride Prolonged-release (SPD503) in Children and Adolescents aged 6 to 17 Years with Attention-Deficit/Hyperactivity Disorder
- Conditions
- Attention-deficit/hyperactivity disorder (ADHD)
- Registration Number
- NL-OMON55836
- Lead Sponsor
- Takeda
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
1. Subject is a male or female aged 6 to 17 years inclusive at the time of
consent/assent.
2. Subject must meet 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)at screening (Visit 1A).
3. Subject 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).
4. Subject has an ADHD-RS-5 total score >=28 at baseline (Visit 2A).
5. Subject has a baseline (Visit 2A) CGI-S score >=4.
6. Subject 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 childbearing
potential is defined as any female subject who is at least aged 9 years or
younger than 9 years and postmenarchal.
7. Subject*s parent or legally authorized representative (LAR) must provide
signature of informed consent. Documentation of assent (if applicable) must be
provided by the subject indicating that the subject 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 and applicable regulations,
before completing any study-related procedures.
8. Subject 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 IMP dose each morning when the subject awakens.
9. Subject has supine and standing blood pressure (BP) measurements within the
95th percentile for age, sex, and height at both screening (Visit 1A) and
baseline (Visit 2A).
10. Subject is functioning at an age-appropriate level intellectually, as
judged by the investigator.
11. Subject is able to swallow intact tablets.
1. Subject 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):
a. Posttraumatic stress disorder (PTSD)
b. Bipolar illness, psychosis, or family history in either biological parent
c. Pervasive developmental disorder
d. Obsessive-compulsive disorder (OCD)
e. Psychosis/schizophrenia
f. Serious tic disorder or a family history of Tourette*s disorder
2. Subject 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.
3. Subject 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.
4. Subject has a clinically important abnormality on the urine drug and/or
alcohol screen at screening.
5. Subject has been physically, sexually, and/or emotionally abused.
6. Subject has any other disorder that as judged by the investigator could
contraindicate TAK-503 or confound the results of the safety and efficacy
assessments.
7. Subject 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 subject and/or could confound the
interpretation of study results.
8. Subject 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.
9. Subject 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.
10. Children aged 6 to 12 years with a body weight <25.0 kg or adolescents aged
>=13 years with a body weight <34.0 kg at screening (Visit 1A) or baseline
(Visit 2A).
11. Subject 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.
12. Subject has a known history or presence of: structural cardiac
abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction
problems (eg, clinically significant heart block or QT interval prolongation),
bradycardia, or exercise-related cardiac events including syncope and
presyncope.
13. Subject has clinically significant ECG findings, as judged by the
investigator, at baseline (Visit 2A).
14. Subject has orthostatic hypotension or a known history of hypertension.
15. Subject has a known family history of sudden cardiac death or ventricular
arrhythmia.
16. Subject is currently using any medication that violates protocol-specified
washout criteria at baseline (Visit 2A), including any ADHD medication or other
prohibited medi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary safety endpoint will be the change from baseline in the CANTAB RTI<br /><br>task.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary safety endpoints will include the following:<br /><br>-CANTAB tasks: RVP, SWM between errors, DMS, and SST<br /><br>-Tanner stage, weight, height, BMI<br /><br>-Vital signs (BP and pulse) and ECG results<br /><br>-BPRS-C total score and scales for Depression, Anxiety, Psychomotor<br /><br>Excitation, Behavior Problems, Withdrawal, Thinking Disturbance, and Organicity<br /><br>-C-SSRS<br /><br>-Specified UKU side effect rating scale items:<br /><br>Asthenia/Lassitude/Increased<br /><br>Fatigability, Sleepiness/Sedation, Increased Duration of Sleep, and<br /><br>Orthostatic<br /><br>Dizziness<br /><br>-PDSS<br /><br>Secondary efficacy endpoints will include the following:<br /><br>-ADHD-RS-5 total score and subscale scores for<br /><br>hyperactivity/impulsivity and<br /><br>inattention domains<br /><br>-CGI-I, calculated from CGI-S<br /><br>-CHIP-CE:PRF<br /><br>-C3PS Total Score and scores for Learning Problems and Executive Functioning<br /><br>subscales</p><br>