E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Autistic disorder, being irritable |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003808 |
E.1.2 | Term | Autistic disorder |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to evaluate the effectiveness (change in level of irritability and related behaviors) and safety and tolerability of the administration of 2 different fixed dose levels of risperidone (an atypical antipsychotic drug) compared with placebo in children or adolescents who have autism, and to evaluate the safety and tolerability of the drug for additional 26 weeks after the initial 6-week study period. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- DSM-IV diagnosis of Autistic Disorder (299.00)
- ABC-I Subscale score of greater than or equal to 18
- CGI-S of greater than or equal to 4
- mental age >18 months, body weight of at least 20 kg, seizure-free for at least 6 consecutive months and if on anticonvulsants must be on a dosage that has been stable for at least 4 weeks
- Medication free for 1 week before the start of the study for all psychotropic drugs, except 4 weeks for fluoxetine and at least 8 weeks for injectable medications
- Female patients must be premenarchal or sexually abstinent or, if heterosexually active, must practice an effective method of birth control. |
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E.4 | Principal exclusion criteria |
- History of prior or current DSM-IV psychotic disorder (e.g., schizophrenia, bipolar disorder, other psychosis), Pervasive Developmental Disorder not otherwise specified (PDD NOS), Asperger's, or Rett's
- Any history of hypersensitivity to risperidone, or its excipients in formulation, or other known drug allergy
- Patients who received risperidone within 3 months before screening (except p.r.n. use)
- Patients who did not demonstrate sufficient clinical response to an adequate trial of risperidone treatment in the past (an adequate trial is defined as a period of at least 4 weeks at an adequate dose)
- Neurologic disorder (e.g., Neuroleptic Malignant Syndrome, seizure disorders that are unstable, seizure activity within the past 6 months)
- History of alcohol or substance dependence within 3 months of screening
- Female subject who is pregnant (positive beta-HCG) or breast feeding
- Patients with existing moderate or severe EPS or history of tardive dyskinesia
- Patients who have received an experimental drug or used an experimental medical device within 3 months before the planned start of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in Aberrant Behavior Checklist Irritability (ABC-I) subscale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Number of participants who had at least 25% improvement in ABC-I
- Change in Clinical Global Impression Severity (CGI-S)
- Number of participants who had Clinical Global Impression Change ratings of much or very much improved.
- Change in Fasting Glucose (mg/dL) at 6 weeks
- Change in Insulin Resistance (IR) at 6 weeks
- Change in Fasting Glucose (mg/dL) at 6 months
- Change in Insulin Resistance (IR) at 6 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |