Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01238575
• Collaborator: Emory University (Other), Massachusetts General Hospital (Other), Seattle Children's Hospital (Other), University of California, Los Angeles (Other), National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 62
• Locations: 5
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 12.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether guanfacine (trade name Intuniv) by itself or in combination with methylphenidate (also known as Ritalin) is helpful for treating hyperactivity in children and adolescents with a Pervasive Developmental Disorders (PDDs).

Condition or Disease	Intervention/Treatment	Phase
Pervasive Development Disorders	Other: placebo; Drug: extended-release guanfacine	Phase 4

Detailed Description

Pervasive Developmental Disorders (PDDs) are a group of conditions that includes Autistic Disorder, Asperger's disorder and so called Pervasive Developmental Disorder - Not Otherwise Specified. Children with PDD show delays in speech and language and reduced social interaction. Some children with PDD have also have problems with overactivity, impulsiveness and distractability. These behaviors are seen in children with Attention Deficit Hyperactivity Disorder (ADHD). Extended release guanfacine (Intuniv) is FDA-approved for the treatment of children with ADHD. The purpose of this study is to evaluate whether Intuniv is an effective treatment for ADHD symptoms in children with PDD.

This study has four parts: an 8-week double-blind trial, an 8-week blinded extension phase (for positive responders only), an 8-week open-label trial, and a 4-week add-on study. Following confirmation of eligibility, participants will be randomly assigned to receive either guanfacine or placebo in the 8-week double-blind trial. Children who show improvement after 8 weeks of treatment will continue on their assigned treatment for an additional 8 weeks (blinded extension phase). Children who show partial improvement with guanfacine will be offered 4 weeks of treatment with guanfacine plus methylphenidate (add-on study). Children who show no improvement on placebo will be offered 8 weeks of treatment with guanfacine (open-label trial). Children who show no improvement on guanfacine will exit the study.

Side effects and treatment response will be assessed at regularly scheduled visits.

The study protocol was formally revised with the Yale University IRB in May 2013 to address an early close to enrollment due to a reduction in funding. The original anticipated enrollment numbers of 112 subjects was reduced to 60 subjects. The study statistician was consulted prior to enrollment closure to address any issues related to statistical power and the adjustments made to the final statiscal analysis plan.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Extended-release guanfacine	Drug: extended-release guanfacine; 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks; Other Names: Intuniv
Placebo Comparator: Inactive placebo	Other: placebo; Administered for up to 8 weeks.

Outcome Measures

Primary Outcome Measures

1. Aberrant Behavior Checklist Hyperactivity Subscale [Week 8]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48.

Secondary Outcome Measures

1. ADHD Rating Scale - Total [Week 8]

   The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity.

2. Aberrant Behavior Checklist Irritability Subscale [8 weeks]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. It is a 58 item checklist which takes about 10 - 15 minutes to complete. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech. The higher the number of items (score), the greater the amount of symptoms. Scores can range from 0 to 45.

3. Aberrant Behavior Checklist Social Withdrawal Subscale [8 weeks]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48.

4. Aberrant Behavior Checklist Sterotypy Subscale [8 weeks]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21.

5. Aberrant Behavior Checklist Inappropriate Speech Subscale [8 weeks]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12.

6. ADHD Rating Scale - Inattention Subscale [8 weeks]

   The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.

7. ADHD Rating Scale - Hyperactivity Subscale [8 weeks]

   The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring,with a higher score indicating greater severity.

8. Aberrant Behavior Checklist Hyperactivity Subscale [Baseline]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48.

9. Aberrant Behavior Checklist Irritability Subscale [Baseline]

   The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. Scores for this subscale can range from 0 to 45.

10. Aberrant Behavior Checklist Social Withdrawal Subscale [Baseline]

    The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48.

11. Aberrant Behavior Checklist Sterotypy Subscale [Baseline]

    The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21.

12. Aberrant Behavior Checklist Inappropriate Speech Subscale [Baseline]

    The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12.

13. ADHD Rating Scale - Inattention Subscale [Baseline]

    The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.

14. ADHD Rating Scale - Hyperactivity Subscale [Baseline]

    The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.

15. ADHD Rating Scale - Total [Baseline]

    The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 14 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of PDD (PDD-NOS, Asperger's Disorder, Autistic Disorder)

• Hyperactivity

• Between ages 5 years 0 months and 13 years 11 months.

• Weight >/= 15 kg (33 lb)

• A mental age of at least 18 months

Exclusion Criteria:

• Prior failed treatment with an adequate trial of guanfacine in the last 2 years

• Concurrent treatment with another psychoactive medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90024
2	Yale University	New Haven	Connecticut	United States	06519
3	Emory University	Atlanta	Georgia	United States	30329
4	Massachusetts General Hospital	Lexington	Massachusetts	United States	02142
5	Seattle Children's Hospital	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Yale University
• Emory University
• Massachusetts General Hospital
• Seattle Children's Hospital
• University of California, Los Angeles
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Lawrence Scahill, MSN, PhD, Emory University
• Principal Investigator: James McCracken, MD, University of California, Los Angeles
• Principal Investigator: Bryan King, MD, Seattle Children's Hospital
• Principal Investigator: Christopher McDougle, MD, Massachusetts General Hospital
• Principal Investigator: James Dziura, MPH, PhD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Scahill L, Aman MG, McDougle CJ, McCracken JT, Tierney E, Dziura J, Arnold LE, Posey D, Young C, Shah B, Ghuman J, Ritz L, Vitiello B. A prospective open trial of guanfacine in children with pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2006 Oct;16(5):589-98.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01238575
• Other Study ID Numbers: 1001006172; R01MH083707
• First Posted: Nov 10, 2010
• Last Update Posted: Mar 31, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Yale University: Pervasive Developmental Disorders; PDD; PDD-NOS; Autistic Disorder; Autism; Asperger's Disorder; Hyperactivity; Attention Deficit Hyperactivity Disorder; ADHD; Medication; Drug; Guanfacine; Intuniv; Placebo; Methylphenidate
• Additional relevant MeSH terms: Hyperkinesis; Disease; Developmental Disabilities; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Guanfacine

Study Results

Participant Flow

Pre-assignment Detail	81 total patients screened. 13 ineligible. 6 Declined

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Period Title: Overall Study
STARTED	30	32
COMPLETED	26	28
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo	Total
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.	Total of all reporting groups
Overall Participants	30	32	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.44 (2.28)	8.39 (2.23)	8.4 (2.25)
Sex: Female, Male (Count of Participants)
Female	4 13.3%	5 15.6%	9 14.5%
Male	26 86.7%	27 84.4%	53 85.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 13.3%	1 3.1%	5 8.1%
Native Hawaiian or Other Pacific Islander	1 3.3%	1 3.1%	2 3.2%
Black or African American	7 23.3%	4 12.5%	11 17.7%
White	17 56.7%	23 71.9%	40 64.5%
More than one race	1 3.3%	3 9.4%	4 6.5%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Aberrant Behavior Checklist Hyperactivity Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	19.3	29.7

2. Secondary Outcome

Title	ADHD Rating Scale - Total
Description	The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	25.2	38.0

3. Secondary Outcome

Title	Aberrant Behavior Checklist Irritability Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. It is a 58 item checklist which takes about 10 - 15 minutes to complete. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech. The higher the number of items (score), the greater the amount of symptoms. Scores can range from 0 to 45.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	13.5	16.1

4. Secondary Outcome

Title	Aberrant Behavior Checklist Social Withdrawal Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	9.8	8.6

5. Secondary Outcome

Title	Aberrant Behavior Checklist Sterotypy Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	3.6	5.9

6. Secondary Outcome

Title	Aberrant Behavior Checklist Inappropriate Speech Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	4.2	5.99

7. Secondary Outcome

Title	ADHD Rating Scale - Inattention Subscale
Description	The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	14.7	19.5

8. Secondary Outcome

Title	ADHD Rating Scale - Hyperactivity Subscale
Description	The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring,with a higher score indicating greater severity.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Least Squares Mean (95% Confidence Interval) [units on a scale]	10.6	18.7

9. Secondary Outcome

Title	Aberrant Behavior Checklist Hyperactivity Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	34.4	34.25

10. Secondary Outcome

Title	Aberrant Behavior Checklist Irritability Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. Scores for this subscale can range from 0 to 45.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	20.3	18.06

11. Secondary Outcome

Title	Aberrant Behavior Checklist Social Withdrawal Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	13.6	12.06

12. Secondary Outcome

Title	Aberrant Behavior Checklist Sterotypy Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	8.53	9.31

13. Secondary Outcome

Title	Aberrant Behavior Checklist Inappropriate Speech Subscale
Description	The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	6.33	6.84

14. Secondary Outcome

Title	ADHD Rating Scale - Inattention Subscale
Description	The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	20.53	20.41

15. Secondary Outcome

Title	ADHD Rating Scale - Hyperactivity Subscale
Description	The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	19.00	19.5

16. Secondary Outcome

Title	ADHD Rating Scale - Total
Description	The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-release Guanfacine	Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks	placebo: Administered for up to 8 weeks.
Measure Participants	30	32
Mean (95% Confidence Interval) [units on a scale]	39.53	39.91

Adverse Events

Arm/Group Title	Extended-release Guanfacine		Inactive Placebo
Arm/Group Description	extended-release guanfacine: 1 mg tablets; flexible dosing up to 4 mg/day for up to 16 weeks		placebo: Administered for up to 8 weeks.
All Cause Mortality
	Extended-release Guanfacine		Inactive Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Extended-release Guanfacine		Inactive Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/32 (0%)
Psychiatric disorders
Aggressive	1/30 (3.3%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Extended-release Guanfacine		Inactive Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/30 (100%)		25/32 (78.1%)
Eye disorders
Blurred Vision	2/30 (6.7%)		0/32 (0%)
Gastrointestinal disorders
Dry Mouth	12/30 (40%)		1/32 (3.1%)
Stomachache	8/30 (26.7%)		4/32 (12.5%)
Constipation	7/30 (23.3%)		2/32 (6.3%)
Nausea	3/30 (10%)		2/32 (6.3%)
Diarrhea	3/30 (10%)		0/32 (0%)
Vomiting	3/30 (10%)		3/32 (9.4%)
Increased Appetite	2/30 (6.7%)		2/32 (6.3%)
General disorders
Fatigue	19/30 (63.3%)		3/32 (9.4%)
Decreased Appetite	13/30 (43.3%)		2/32 (6.3%)
Emotional/tearful	12/30 (40%)		3/32 (9.4%)
Irritability	11/30 (36.7%)		3/32 (9.4%)
Increased Energy	9/30 (30%)		6/32 (18.8%)
Weakness	3/30 (10%)		1/32 (3.1%)
Fever	1/30 (3.3%)		3/32 (9.4%)
Nervous system disorders
Drowsiness	26/30 (86.7%)		3/32 (9.4%)
Headache	9/30 (30%)		6/32 (18.8%)
Dizziness	3/30 (10%)		2/32 (6.3%)
Motor Tics	1/30 (3.3%)		2/32 (6.3%)
Psychiatric disorders
Anxiety	9/30 (30%)		1/32 (3.1%)
Mid sleep awakening	9/30 (30%)		2/32 (6.3%)
Increased Repetitive Behavior	5/30 (16.7%)		3/32 (9.4%)
Aggression	5/30 (16.7%)		2/32 (6.3%)
Depressed Mood	4/30 (13.3%)		1/32 (3.1%)
Self-injury	3/30 (10%)		0/32 (0%)
Trouble Falling Asleep	3/30 (10%)		2/32 (6.3%)
Silly	3/30 (10%)		5/32 (15.6%)
Excessive Talking	2/30 (6.7%)		9/32 (28.1%)
Nightmares	2/30 (6.7%)		0/32 (0%)
Renal and urinary disorders
Enuresis	2/30 (6.7%)		2/32 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough/Congestion	4/30 (13.3%)		4/32 (12.5%)
Skin and subcutaneous tissue disorders
Skin rash/Eczema	2/30 (6.7%)		4/32 (12.5%)
Skin Picking	1/30 (3.3%)		3/32 (9.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.