Study of Paliperidone ER in Adolescents and Young Adults With Autism

• Sponsor: Indiana University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00549562
• Collaborator: Ortho-McNeil Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This 8-week, prospective open-label study will investigate the effectiveness and tolerability of paliperidone ER in adolescents and young adults with autism. Hypothesis:Paliperidone Er will be well tolerated and efficacious for reducing aggression, self-injury, and irritability in adolescents and young adults.

Condition or Disease	Intervention/Treatment	Phase
Autism	Drug: Paliperidone ER	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Open-Label Study of Paliperidone ER in Adolescents and Young Adults With Autism
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: Paliperidone ER 8-Week Open-Label	Drug: Paliperidone ER; Starting dose is 3 mg per day. Can be titrated up to a maximum dose of 9 mg per day.; Other Names: Invega

Outcome Measures

Primary Outcome Measures

1. The Clinical Global Impression-Improvement(CGI-I) [Week 8]

   The CGI Global Improvement (CGI-I) is a clinician-rate scale designed to take into account all factors to arrive at an assessment of severity and response to treatment, including parent report, parent-rated measures, teacher-rated measures, and clinician-rated measures. The CGI-I is rated from 1 to 7 (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) at a single time-point.

2. The Aberrant Behavior Checklist [Week 8]

   The Aberrant Behavior Checklist (ABC) is a 58-item measure of maladaptive behaviors and is used as a measure of drug effects. Each item is rated from 0 (not at all to 3 (severe). The ABC has 5 subscales:Irritability (15 items) ranging from 0 (not at all) to 45 (severe), Hyperactivity (16 items) ranging from 0 (not at all) to 48 (severe), Social Withdrawal (16 items) ranging from 0 (not at all) to 48 (severe), Stereotypy (7 items) ranging from 0 (not at all) to 21 (severe) and Inappropriate Speech (4 items) ranging from 0 (not at all) to 12 (severe).

Secondary Outcome Measures

1. The Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders [Week 8]

   The Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CY-BOCS-PDD) is semi-structured clinician rating scale designed to rate the current severity of repetitive behavior in children and adolescents with PDD. The scale consists of 5 items: Time Spent, Interference, Distress, Resistance and Control. Each item is scored from 0 (None) to 4 (Extreme). The scale yields a Total Score from 0 (least symptomatic) to 20 (most symptomatic). Higher scores indicate greater severity of repetitive behavior.

2. The Social Responsiveness Scale [Week 8]

   The Social Responsiveness Scale (SRS) is a 65-item parent completed scale that assesses social awareness, social cognition, social communication, social motivation and autistic mannerisms. Each item is scored from 1 (not true) to 3 (almost always true). Interpretation in this study is based on a total score that is proportional to the level of impairment in reciprocal social behavior. Scores within 0-53 are within normal limits. Scores within 54-86 indicate mild to moderate impairment. Scores above 87 indicate severe impairment.

3. The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain [Week 8]

   The VABS Maladaptive Behavior Domain measures undesirable behaviors that may interfere with an individual's adaptive functioning. The Maladaptive Domain consists two parts. Part I contains 27 minor maladaptive items and Part II contains 9 serious maladaptive behaviors. Each item is scored from 0 (never or seldom engages in the activity) to 2(usually or habitually engages in the activity). Part 1 yields a score of 0 to 54. Part II yields a score of 0 to 18. Both parts are combined to make a Total Score of 0 to 72. High scores of maladaptive behaviors reflect more negative behavior.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females between ages of 12 and 21 years

• Tanner Sage III or IV (post-pubertal)

• Diagnostic and Statistical Manual Fourth Edition Text-Revised (DSM-IV-TR) diagnosis of autism

• Outpatient

• Ability to swallow pills

• Antipsychotic medication-free for at least 2 weeks

• Score of 4 or more on the Clinical Global Impressions Severity Scale

• Score of 18 or higher on the Aberrant Behavior Checklist Irritability Scale

• Mental age of 18 months or greater based on testing

• Subjects must be in good physical health

Exclusion Criteria:

• Asperger's Disorder, Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS), Rett's Disorder, childhood disintegrative disorder, schizophrenia, bipolar disorder, Fragile X Syndrome, Tuberous Sclerosis

• A significant medical condition

• An active seizure disorder

• Females who are pregnant

• Evidence of a prior adequate trial of paliperidone ER

• History of neuroleptic malignant syndrome

• Hypersensitivity to paliperidone ER

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Riley Child & Adolescent Psychiatry Clinic- Riley Hospital	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University School of Medicine
• Ortho-McNeil Janssen Scientific Affairs, LLC

Investigators

• Study Director: David Dunn, MD, Indiana Univerity School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Stigler KA, Mullett JE, Erickson CA, Posey DJ, McDougle CJ. Paliperidone for irritability in adolescents and young adults with autistic disorder. Psychopharmacology (Berl). 2012 Sep;223(2):237-45. doi: 10.1007/s00213-012-2711-3. Epub 2012 May 3.

• Responsible Party: Indiana University School of Medicine
• ClinicalTrials.gov Identifier: NCT00549562
• Other Study ID Numbers: 0709-24; R076477-AUT-4002
• First Posted: Oct 26, 2007
• Last Update Posted: May 16, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Indiana University School of Medicine: Autistic Disorder
• Additional relevant MeSH terms: Autistic Disorder; Paliperidone Palmitate

Study Results

Participant Flow

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Period Title: Overall Study
STARTED	25
COMPLETED	23
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Overall Participants	25
Age (Count of Participants)
<=18 years	20 80%
Between 18 and 65 years	5 20%
>=65 years	0 0%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	15.36
Sex: Female, Male (Count of Participants)
Female	4 16%
Male	21 84%
Region of Enrollment (participants) [Number]
United States	25 100%
Clinical Global Impressions-Improvement (CGI-I) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.0 (0.0)
The Aberrant Behavior Checklist (units on a scale) [Mean (Standard Deviation) ]
ABC-Irritability	30.3 (6.5)
ABC-Hyperactivity	34.7 (8.9)
ABC-Social Withdrawal	17.2 (12.5)
ABC-Stereotypy	12.5 (6.7)
ABC-Inappropriate Speech	7.5 (4.4)
Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16 (3)
The Social Responsiveness Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	122.6 (18.4)
The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain (units on a scale) [Mean (Standard Deviation) ]
VABS Maladaptive Behavior Subscale Part I	28.9 (6.3)
VABS Maladaptive Behavior Subscale Part II	8.8 (6.4)
VABS Maladaptive Behavior Subscale Total	37.4 (8.2)

Outcome Measures

1. Primary Outcome

Title	The Clinical Global Impression-Improvement(CGI-I)
Description	The CGI Global Improvement (CGI-I) is a clinician-rate scale designed to take into account all factors to arrive at an assessment of severity and response to treatment, including parent report, parent-rated measures, teacher-rated measures, and clinician-rated measures. The CGI-I is rated from 1 to 7 (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) at a single time-point.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Measure Participants	25
Mean (Standard Deviation) [units on a scale]	1.8 (1.3)

2. Primary Outcome

Title	The Aberrant Behavior Checklist
Description	The Aberrant Behavior Checklist (ABC) is a 58-item measure of maladaptive behaviors and is used as a measure of drug effects. Each item is rated from 0 (not at all to 3 (severe). The ABC has 5 subscales:Irritability (15 items) ranging from 0 (not at all) to 45 (severe), Hyperactivity (16 items) ranging from 0 (not at all) to 48 (severe), Social Withdrawal (16 items) ranging from 0 (not at all) to 48 (severe), Stereotypy (7 items) ranging from 0 (not at all) to 21 (severe) and Inappropriate Speech (4 items) ranging from 0 (not at all) to 12 (severe).
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Measure Participants	25
ABC-Irritability	12.6 (9.1)
ABC-Hyperactivity	17.4 (11.5)
ABC-Social Withdrawal	7.6 (8.8)
ABC-Stereotypy	6.4 (5.1)
ABC-Inappropriate Speech	3.4 (3.8)

3. Secondary Outcome

Title	The Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders
Description	The Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CY-BOCS-PDD) is semi-structured clinician rating scale designed to rate the current severity of repetitive behavior in children and adolescents with PDD. The scale consists of 5 items: Time Spent, Interference, Distress, Resistance and Control. Each item is scored from 0 (None) to 4 (Extreme). The scale yields a Total Score from 0 (least symptomatic) to 20 (most symptomatic). Higher scores indicate greater severity of repetitive behavior.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Measure Participants	25
Mean (Standard Deviation) [units on a scale]	11.9 (4.0)

4. Secondary Outcome

Title	The Social Responsiveness Scale
Description	The Social Responsiveness Scale (SRS) is a 65-item parent completed scale that assesses social awareness, social cognition, social communication, social motivation and autistic mannerisms. Each item is scored from 1 (not true) to 3 (almost always true). Interpretation in this study is based on a total score that is proportional to the level of impairment in reciprocal social behavior. Scores within 0-53 are within normal limits. Scores within 54-86 indicate mild to moderate impairment. Scores above 87 indicate severe impairment.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Measure Participants	25
Mean (Standard Deviation) [units on a scale]	100.9 (20.4)

5. Secondary Outcome

Title	The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain
Description	The VABS Maladaptive Behavior Domain measures undesirable behaviors that may interfere with an individual's adaptive functioning. The Maladaptive Domain consists two parts. Part I contains 27 minor maladaptive items and Part II contains 9 serious maladaptive behaviors. Each item is scored from 0 (never or seldom engages in the activity) to 2(usually or habitually engages in the activity). Part 1 yields a score of 0 to 54. Part II yields a score of 0 to 18. Both parts are combined to make a Total Score of 0 to 72. High scores of maladaptive behaviors reflect more negative behavior.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
Measure Participants	25
VABS Maladaptive Behavior Subscale-Part I	19.0 (6.9)
VABS Maladaptive Behavior Subjscale Part II	6.4 (3.4)
VABS Maladaptive Behavior Subscale Total	25.1 (8.8)

Adverse Events

Time Frame	Eight Weeks
Arm/Group Title	Paliperidone ER
Arm/Group Description	8-Week Open-Label Paliperidone ER: Starting dose is 3 mg per day, with the option to increase the dose by 3 mg/day on a weekly basis for 4 weeks to a maximum dose of 12 mg per day.
All Cause Mortality
	Paliperidone ER
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Serious Adverse Events
	Paliperidone ER
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Paliperidone ER
	Affected / at Risk (%)	# Events
Total	21/25 (84%)
Cardiac disorders
Palpitations	1/25 (4%)	1
Gastrointestinal disorders
Excessive Appetite	9/25 (36%)	9
Constipation	3/25 (12%)	3
Diarrhea	2/25 (8%)	2
Dyspepsia	1/25 (4%)	1
General disorders
Tiredness	7/25 (28%)	7
Rhinitis/cough	8/25 (32%)	8
Excessive saliva	2/25 (8%)	2
Dry Mouth	1/25 (4%)	1
Metabolism and nutrition disorders
Weight Gain	9/25 (36%)	9
Nervous system disorders
Tremor	1/25 (4%)	1
Headache	1/25 (4%)	1
Tic	1/25 (4%)	1
Akathisia	1/25 (4%)	1
Psychiatric disorders
Insomnia	3/25 (12%)	3
Renal and urinary disorders
Enuresis	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Rash	2/25 (8%)	2

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.