Autism
Conditions
Keywords
Autistic Disorder
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.
Interventions
DRUGPaliperidone ER
Starting dose is 3 mg per day. Can be titrated up to a maximum dose of 9 mg per day.
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Indiana University School of Medicine
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone ER 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. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 1 |
Baseline characteristics
| Characteristic | Paliperidone ER |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 15.36 Years |
| Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders | 16 units on a scale STANDARD_DEVIATION 3 |
| Clinical Global Impressions-Improvement (CGI-I) | 4.0 units on a scale STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 21 Participants |
| The Aberrant Behavior Checklist ABC-Hyperactivity | 34.7 units on a scale STANDARD_DEVIATION 8.9 |
| The Aberrant Behavior Checklist ABC-Inappropriate Speech | 7.5 units on a scale STANDARD_DEVIATION 4.4 |
| The Aberrant Behavior Checklist ABC-Irritability | 30.3 units on a scale STANDARD_DEVIATION 6.5 |
| The Aberrant Behavior Checklist ABC-Social Withdrawal | 17.2 units on a scale STANDARD_DEVIATION 12.5 |
| The Aberrant Behavior Checklist ABC-Stereotypy | 12.5 units on a scale STANDARD_DEVIATION 6.7 |
| The Social Responsiveness Scale | 122.6 units on a scale STANDARD_DEVIATION 18.4 |
| The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain VABS Maladaptive Behavior Subscale Part I | 28.9 units on a scale STANDARD_DEVIATION 6.3 |
| The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain VABS Maladaptive Behavior Subscale Part II | 8.8 units on a scale STANDARD_DEVIATION 6.4 |
| The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain VABS Maladaptive Behavior Subscale Total | 37.4 units on a scale STANDARD_DEVIATION 8.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 21 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
The Aberrant Behavior Checklist
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone ER | The Aberrant Behavior Checklist | ABC-Irritability | 12.6 units on a scale | Standard Deviation 9.1 |
| Paliperidone ER | The Aberrant Behavior Checklist | ABC-Hyperactivity | 17.4 units on a scale | Standard Deviation 11.5 |
| Paliperidone ER | The Aberrant Behavior Checklist | ABC-Social Withdrawal | 7.6 units on a scale | Standard Deviation 8.8 |
| Paliperidone ER | The Aberrant Behavior Checklist | ABC-Stereotypy | 6.4 units on a scale | Standard Deviation 5.1 |
| Paliperidone ER | The Aberrant Behavior Checklist | ABC-Inappropriate Speech | 3.4 units on a scale | Standard Deviation 3.8 |
Primary
The Clinical Global Impression-Improvement(CGI-I)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | The Clinical Global Impression-Improvement(CGI-I) | 1.8 units on a scale | Standard Deviation 1.3 |
Secondary
The Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | The Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders | 11.9 units on a scale | Standard Deviation 4 |
Secondary
The Social Responsiveness Scale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | The Social Responsiveness Scale | 100.9 units on a scale | Standard Deviation 20.4 |
Secondary
The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone ER | The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain | VABS Maladaptive Behavior Subjscale Part II | 6.4 units on a scale | Standard Deviation 3.4 |
| Paliperidone ER | The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain | VABS Maladaptive Behavior Subscale Total | 25.1 units on a scale | Standard Deviation 8.8 |
| Paliperidone ER | The Vineland Adaptive Behavior Scales (VABS) - Maladaptive Behavior Domain | VABS Maladaptive Behavior Subscale-Part I | 19.0 units on a scale | Standard Deviation 6.9 |