Study to assess the long term safety and efficacy of Guanfacine- Hydrochloride in Children and Adolescents aged 6-17 years old, with Attention- Deficit/Hyperactivity Disorder

INTERVENTION: 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 Current Sponsor code: SPD503 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Prolonged‐release tablet Route of administration of the placebo: Oral use 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 Current Sponsor code: SPD503 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Pharmaceutical form of the placebo: Prolonged‐release tablet Route of administration of the placebo: Oral use 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 Current Sponsor code: SPD503 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Pharmaceutical form of the placebo: Prolonged‐release tablet Route of administration of the placebo: Oral use 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 Current Sponsor code: SPD503 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Pharmaceutical form of the placebo: Prolonged‐release tablet Route of administration of the placebo: Oral use CONDITION: Attention‐Deficit/Hyperactive Disorder (ADHD) ; MedDRA version: 14.1 Level: LLT Classification code 10068451 Term: ADHD, combined type System Organ Class: 100000004873 ; MedDRA version: 14.1 Level: LLT Classification code 10068453 Term: ADHD, predominantly inattentive type System Organ Class: 100000004873 ; MedDRA version: 14.1 Level: LLT Classification code 10068452 Term: ADHD, predominantly hyperactive‐impulsive type System Organ Class: 100000004873 ; MedDRA version: 14.1 Level: LLT Classification code 10064104 Term: ADHD System Organ Class: 100000004873 Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] SECONDARY OUTCOME: Secondary end point(s): Time to treatment failure during the double‐blind randomised‐withdrawal phase (days) is a key secondary endpoint.; Other endpoints are ADHD‐RS‐IV total scores, CGI‐S scores, CGI‐I scores, HUI‐2/3, and WFIRS‐P results. Timepoint(s) of evaluation of this end point: At Phase 2 visits (Visits 14‐23/ Early Termination) PRIMARY OUTCOME: Main Objective: The primary efficacy outcome for each subject is treatment failure during the double‐blind randomised‐withdrawal phase (Phase 2). The primary efficacy analysis will compare treatment failure rates between treatments (SPD503 and placebo) for all subjects who enter Phase 2 using a Cochran‐Mantel‐Haenszel (CMH) test stratified by age group and country. Subjects who discontinue for any reason during the randomised‐withdrawal phase will be classed as treatment failures for the primary analysis. The null hypothesis states that there is no difference in treatment failure rate between SPD503 and placebo, with the 2‐sided alternative of a non‐zero difference between groups. Primary end point(s): The primary efficacy outcome for each subject is treatment failure during the double‐blind randomised‐withdrawal phase (Phase 2), defined as a >/=50% increase (worsening) in ADHD RS‐IV total score at 2 consecutive Phase 2 visits (Visits 14‐23/ Early Termination) relative to Visit 13 and a >/=2 point increase in CGI‐S score relative to CGI‐S at Visit 13 at the corresponding Phase 2 visits. Secondary Objective: 1. To assess the long‐term efficacy of SPD503 using the clinician administered Attention deficit/Hyperactivity Disorder Rating Scale‐IV (ADHD‐RS‐IV) total score.; 2. To assess the long‐term efficacy of SPD503 using the clinician administered Global Impressions‐ Severity of Illness Scale (CGI‐S).; 3. To assess the efficacy of SPD503 using the clinician administered Clinical Global Impressions Improvement Scale (CGI‐I); 4. To evaluate efficacy on ADHD functional outcomes as measured by the Weiss Functional Impairment Rating Scale‐Parent (WFIRS‐P).; 5. 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). ; 6. To evaluate the long‐term safety of SPD503 based on treatment‐emergent adverse events (TEAEs), specific evaluation of blood pressure and pulse, clinical laboratory tests, electrocardiogram (ECG) results, and results from the Columbia‐Suicide Severity Rating Scale (C‐SSRS). Timepoint(s) of evaluation of this end point: At 2 consecutive Phase 2 visits (Visits 14‐23/ Early Termination) INCLUSION CRITERIA: 1. Male or female, aged 6 to 17 years at the time of consent/assent at Screening/Visit 1. 2. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th ed. 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). 3. Subject has a minimum ADHD‐RS‐IV total score of 32 at Enrolment/Visit 2. 4. Subject has a minimum CGI‐S score of 4 at Enrolment/Visit 2. 5. Subject is able to swallow intact tablets. Are the trial subjects under 18? yes Number of subjects for this age range: 510 F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range