Dose-optimization in Adolescents Aged 13-17 Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD) Using Extended-release Guanfacine HCl

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01081132
First received: March 3, 2010
Last updated: June 6, 2014
Last verified: April 2014
  Purpose

To assess the efficacy of optimized Extended-release Guanfacine Hydrochloride compared with placebo in the treatment of adolescents aged 13-17 years with a diagnosis of ADHD as measured by the ADHD-RS-IV


Condition Intervention Phase
Attention-Deficit/Hyperactivity Disorder
Drug: Extended-release Guanfacine Hydrochloride
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Double-blind, Randomized, Multi-center, Placebo Controlled, Dose-optimization Study Evaluating the Safety, Efficacy, and Tolerability of Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Adolescents Aged 13-17 Years Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD)

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 13 [ Time Frame: Baseline through week 13 ] [ Designated as safety issue: No ]
    The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.


Secondary Outcome Measures:
  • Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale at the Last On-Treatment Assessment [ Time Frame: Baseline through week 13 ] [ Designated as safety issue: No ]
    CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill)

  • Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Learning and School Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Family Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Family Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Global Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Risk Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Risk Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Social Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Social Domain consists of 7-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Child Self-Concept Domain consists of 3-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). The Life Skills Domain consists of 10-items. Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.

  • Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores at the Last On-Treatment Assessment [ Time Frame: weeks 1 through 13 ] [ Designated as safety issue: No ]
    Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

  • Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at Week 13 [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    Behavior Rating Inventory of Executive Function (BRIEF) is a questionnaire composed of three indices: Global Executive Composite, Behavioral Regulation Index, and Metacognition Index. Items are rated 1 (never), 2 (sometimes), and 3 (often). The Global Executive Composite consists of 72 items with scoring ranging from 72 to 216. The Behavioral Regulation Index score is the total of 28 items and ranges from 28 to 84. The Metacognition Index score is the total of 44 items and ranges from 44 to 132. Lower scores reflect better functioning.

  • Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 13 [ Time Frame: Baseline through week 13 ] [ Designated as safety issue: Yes ]
    The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 item questionnaire scored on a scale from 0 (never) to 4 (always/very often). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness.

  • Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Last On-Treatment Assessment [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: Yes ]
    The BPRS-C characterizes childhood behavioral and emotional symptomatology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.

  • Structure Side-Effect Questionnaire (SSEQ) [ Time Frame: Through week 16 ] [ Designated as safety issue: Yes ]
    The Structured Side-effect Questionnaire is a simple checklist of 17 side effects. The subject indicates whether a side effect has occurred since the last visit by marking 'yes' or 'no' on the checklist for each of the events listed.

  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Through week 16 ] [ Designated as safety issue: Yes ]
    C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.


Enrollment: 314
Study Start Date: September 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Extended-release Guanfacine HCl Drug: Extended-release Guanfacine Hydrochloride
The test product will be provided as 1, 2, 3, and 4mg tablets. Subjects will be administered a once-daily dose between 1-7mg/day depending on weight.
Other Name: Intuniv
Placebo Comparator: Placebo Other: Placebo
Matching placebo will be provided as 1,2,3, and 4mg tablets. Subjects will be administered a once-daily dose of placebo between 1-7mg/day depending on weight.

  Eligibility

Ages Eligible for Study:   13 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged 13-17 years at the time of consent/assent (screening only).
  2. Subject's parent or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent 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 (ICH) Good Clinical Practice (GCP) Guidance E6 (1996) and applicable regulations before completing any study-related procedures at screening.
  3. Subject meets Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, combined subtype, or hyperactive/impulsive subtype, based on a detailed psychiatric evaluation using the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (K SADS PL) at screening (re-confirm if baseline visit is >35 days from screening).
  4. Subject has a minimum ADHD-RS-IV total score of 32 at baseline.
  5. Subject has a minimum CGI-S score of 4 at baseline.
  6. Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
  7. Subject and parent/LAR understand, are able, willing and likely to fully comply with the study procedures and restrictions defined in this protocol.
  8. Subject is able to swallow intact tablets.
  9. All females must have a negative serum beta human Chorionic Gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy test at baseline. Female subjects must abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.
  10. Subject has a supine and standing blood pressure (BP) measurement within the 95th percentile for age, gender, and height.

Exclusion Criteria:

  1. Subject has a current, controlled (requiring a prohibited medication or behavioral modification program) or uncontrolled, comorbid psychiatric diagnosis [except Oppositional Defiant Disorder (ODD), but including all anxiety disorders (except simple phobias)], all major depressive disorders (dysthymia allowed unless medication required), and any severe comorbid Axis II disorders or severe Axis I disorders such as post traumatic stress disorder, bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder, substance abuse disorder, or other symptomatic manifestations that, in the opinion of the Investigator, contraindicate SPD503 treatment or confound efficacy or safety assessments.
  2. Subject has any condition or illness including clinically significant abnormal screening 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.
  3. Subject 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 pre-syncope, or clinically significant bradycardia.
  4. Subject has any abnormal or clinically significant ECG findings as judged by the Investigator with consideration of the central ECG interpretation.
  5. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
  6. Current use of any prohibited medication, including herbal supplements that affect blood pressure, heart rate, 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) at baseline.
  7. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM IV-TR (with the exceptions of nicotine) within the last six months.
  8. Subject has taken another investigational product within 30 days prior to baseline.
  9. Subject is significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at screening. Significantly overweight is defined as a BMI >95th percentile for this study.
  10. Body weight of less than 34.0kg or greater than 91.0kg at screening.
  11. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD503.
  12. Clinically important abnormality on urine drug and/or alcohol screen (excluding the subject's current ADHD stimulant if applicable).
  13. Subject is female and is pregnant or currently lactating.
  14. Subject failed screening or was previously enrolled in this study.
  15. Subject who is currently considered a suicide risk, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating suicidal ideation.
  16. History of failure to respond to an adequate trial (consisting of an appropriate dose and adequate duration of therapy), in the opinion of the Investigator, of an α2-agonist for the treatment of ADHD.
  17. Subject has a history of a seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years) or a history of a tic disorder (including Tourette's syndrome).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01081132

  Show 54 Study Locations
Sponsors and Collaborators
Shire
Investigators
Study Director: Brigitte Robertson, MD Shire Inc.
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01081132     History of Changes
Other Study ID Numbers: SPD503-312, 2011-002221-21
Study First Received: March 3, 2010
Results First Received: March 26, 2014
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Guanfacine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014