Attention-Deficit/Hyperactivity Disorder (ADHD) MedDRA version: 14.1 Level: LLT Classification code 10068451 Term: ADHD, combined type System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 14.1 Level: LLT Classification code 10068453 Term: ADHD, predominantly inattentive type System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 14.1 Level: LLT Classification code 10068452 Term: ADHD, predominantly hyperactive-impulsive type System Organ Class: 10037175 - Psychia
Conditions
Interventions
Trade Name: INTUNIV™
Product Name: Guanfacine Hydrochloride
Product Code: SPD503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: GUANFACINE HYDROCHLORIDE
CAS Number: 29110-48-3
Curr
Sponsors
Shire Pharmaceutical Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 6 to 17 years at the time of consent/assent at Screening (Visit 1). 2. Subject’s parent or legally authorised representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) 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 Conference on Harmonisation Good Clinical Practice Guidance E6, and applicable regulations before completing any study-related procedures at Screening (Visit 1). 3. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV TR) criteria for a primary diagnosis of ADHD, combined sub-type, hyperactive/impulsive sub type or inattentive sub-type, based on a detailed psychiatric evaluation using the Kiddie Schedule for Affective Disorders and Schizophrenia – Present and Lifetime version (K-SADS-PL). 4. Subject has a minimum ADHD-RS-IV total score of 32 at Baseline (Visit 2). 5. Subject has a minimum CGI-S score of 4 at Baseline (Visit 2). 6. Subject is functioning at an age-appropriate level intellectually, as judged by the Investigator. 7. Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study procedures and restrictions defined in this protocol. 8.Subject is able to swallow intact tablets and capsules. 9.Subject who is a female of child-bearing potential (FOCP), defined as >/=9 years of age or =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject has a current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, co-morbid psychiatric diagnosis [except oppositional defiant disorder (ODD)], including any severe co-morbid Axis II disorders or severe Axis I disorders such as post traumatic stress disorder (PTSD), bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder (OCD), substance abuse disorder, or other symptomatic manifestations or lifetime history of bipolar illness, psychosis or conduct disorder that, in the opinion of the Investigator, contraindicate treatment with SPD503 or Strattera or confound efficacy or safety assessments. 2. Subject is well-controlled on their current medication, with acceptable tolerability, and the parent/caregiver does not object to the current medication. 3. Subject has any condition or illness including clinically significant abnormal Screening (Visit 1) laboratory values which, in the opinion of the Investigator, represents an inappropriate risk to the subject and/or could confound the interpretation of the study. Mild stable asthma treated without the use of beta-2 agonist is not exclusionary. 4. Subject has a known history or presence of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (eg, clinically significant heart block or QT interval prolongation), exercise-related cardiac events including syncope and pre-syncope, or clinically significant bradycardia. 5. Subject has a known family history of sudden cardiac death, ventricular arrhythmia, or QT prolongation. 6. Subjects with orthostatic hypotension or a known history of hypertension. 7. Subject has glaucoma. 8. Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory’s interpretation. 9. Subject has a history of a seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years) or the presence of a serious tic disorder including Tourette’s Syndrome. 10. Current use of any prohibited medication or other medications, including monoamine oxidase inhibitors, herbal supplements, that affect BP or heart rate, CYP2D6 inhibitors, medications known to prolong the QT/QTc interval, medications that lower seizure threshold, pressor agents, beta-2 agonists, medications that affect noradrenaline, medications 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 [ie, antihistamines]) in violation of the protocol specified washout criteria at Baseline (Visit 2). 11. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM-IV (with the exception of nicotine) within the last 6 months. 12. Subject has taken another investigational product within 30 days prior to Baseline (Visit 2). 13. Subject is significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at the Screening (Visit 1). Significantly overweight is defined as a BMI >95th percentile. 14. Children aged 6-12 years with a body weight of less than 25.0kg or adolescents aged 13-17 years with a body weight of less than 34.0kg or greater than 91.0kg at Screening (Visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy analysis will be performed on the change from baseline for the ADHD-RS-IV total score at Visit 15 using Last-Observation-Carried Forward (LOCF) methodology, for all subjects randomised and receiving study drug. The mean change from baseline will be compared between treatments using an Analysis of Covariance (ANCOVA) model. The primary treatment comparison is SPD503 versus placebo. The ANCOVA model will include treatment group (the effect of interest), the corresponding baseline score (the covariate), and the blocking factors age group (6-12 years or 13-17 years) and country. The null hypothesis states that there is no difference between SPD503 and placebo, with the 2-sided alternative of a non-zero difference between groups. ;Secondary Objective: 1. To evaluate efficacy based on the clinician’s global impressions of ADHD severity and improvement as measured by the Clinical Global Impression-Severity (CGI-S) Scale and the Clinical Global Impression Improvement (CGI-I) Scale. 2. To evaluate efficacy on ADHD functional outcomes as measured by the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). 3. To assess the impact of treatment on the perception of health state preferences using the Health Utilities Index-Mark 2 and Mark 3 (HUI-2/3). 4. To evaluate the safety of SPD503 and STRATTERA based on the occurrence of treatment-emergent adverse events (TEAEs), electrocardiogram (ECG) results, vital signs, clinical laboratory results, and results from the Brief Psychiatric Rating Scale for Children (BPRS-C), a structured side-effect questionnaire, and Columbia-Suicide Severity Rating Scale. 5. To evaluate the efficacy of STRATTERA compared to placebo based on ADHD-RS, CGI-I, CGI-S, and HUI-2/3. ;Primary end point(s): The primary efficacy analysis will be performed on the change from baseline for the ADHD-RS-IV total score at Visit 15 using LOCF methodology, for the FAS. The mean change from baseline will be compared between trea | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CGI-S scores, CGI-I scores, HUI2/3 results, and WFIRS-P results. ;Timepoint(s) of evaluation of this end point: For each visit and study endpoint (Visit 15 (Week 10 children aged 6-12 years and Week 13 adolescents aged 13-17 years)) | — |
Countries
Austria, Bulgaria, Canada, European Union, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Programs Leadership
Shire Pharmaceutical Development Ltd
Outcome results
None listed