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 |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008525 |
E.1.2 | Term | Childhood schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 primary objective of this study is to evaluate the efficacy, safety and tolerability of three weight-based, fixed-dose groups of paliperidone ER (to fully explore the tolerability range) as
compared with placebo in adolescent subjects 12 to 17 years of age, inclusive, with schizophrenia. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to:
• Assess the change in the global impression of severity of illness
associated with the use of paliperidone ER compared with placebo as measured by the Clinical Global Impression Severity (CGI-S) scale.
• Assess the benefits in psychological, social, and school functioning associated with treatment with paliperidone ER compared with placebo as measured by the Children's Global Assessment Scale (CGAS).
• Explore the pharmacokinetics of paliperidone ER and the relationship between its pharmacokinetics and the results of the efficacy parameters (e.g., Positive and Negative Syndrome Scale [PANSS]) and safety parameters (e.g., extrapyramidal symptoms
[EPS], adverse events) of interest.
An exploratory secondary objective is to assess the effect on sleep
associated with treatment with paliperidone ER as measured by the sleep Visual Analog Scale (VAS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males or females between 12 and 17 years of age, inclusive, with a
body weight of at least 29 kg, who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria for schizophrenia at least 1 year before screening and who had a PANSS total score between 60 and 120, inclusive, at screening and baseline. Eligible subjects were otherwise physically healthy based on medical history, physical examination, electrocardiogram (ECG), and laboratory
test results. |
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E.4 | Principal exclusion criteria |
• Subjects who, at screening, met the DSM-IV criteria for dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance-induced psychotic disorder.
• Subjects with mild, moderate, or severe mental retardation (ie,
documented intelligence quotient [IQ] <70), established by previous IQ testing or history;
• History or presence of circumstances that could have increased the risk of the occurrence of torsade de pointes or sudden death in
association with the use of drugs that prolong the QT interval corrected for heart rate (QTc) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome Measures:
•Change in the PANSS Total Score From Baseline to the Last
Postrandomization Assessment in the Double-blind Period of the
Study. The Positive and Negative Syndrome Scale (PANSS) measures the severity of psychotic symptoms of schizophrenia. Scores range from 30 to 210, where 30=best and 210=worst. The change in PANSS total score for all eligible subjects was measured from the beginning of the study to the end. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
According to time and events schedule over 6 week duration of study |
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E.5.2 | Secondary end point(s) |
Secondary Outcome Measures:
•Change From Baseline to End Point in Clinical Global Impression-
Severity (CGI-S) Scale
The CGI-S rating scale was used to assess the severity of a subject's overall clinical condition. Scores range from 1 to 7, where 1=best and 7=worst.
•Change From Baseline to End Point in Children's Global Assessment (CGAS) Score
The CGAS score assesses psychological, social, and school functioning for children 6 to 17 years of age. Scores range from 1 to 100, where 100=best and 1=worst.
•Change From Baseline to End Point in Sleep Visual Analog Scale (VAS) for Quality of Sleep.
The sleep VAS for sleep quality is a scale for measuring the quality of sleep experienced by a patient. Scores range from 0 to 100, where 100=best and 0=worst.
•Change From Baseline to End Point in Sleep VAS for Daytime
Drowsiness
The sleep VAS for daytime drowsiness is a scale for measuring the
drowsiness experienced by a patient. Scores range from 0 to 100,
where 100=best and 0=worst. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
According to time and events schedule over 6 week duration of study |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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 | Yes |
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 | 4 |
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 | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
India |
Russian Federation |
Ukraine |
United States |
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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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Last visit of last subject undergoing trial |
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E.8.9 Initial estimate of the duration of the trial |