| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008525 |
| E.1.2 | Term | Childhood schizophrenia |
|
| 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 |
OBJECTIVES:
The primary objective of this study is to evaluate the long-term (2-year) safety and tolerability of paliperidone ER in at least 100 adolescent subjects (12 to 17 years of age, inclusive) with schizophrenia.
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| E.2.2 | Secondary objectives of the trial |
Exploratory secondary objectives of this study are to:
· Assess the effect of paliperidone ER on the long-term symptoms of schizophrenia as measured by the changes in the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores
· Assess the global improvement in severity of illness associated with treatment with paliperidone ER 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 as measured by the Children’s Global Assessment Scale (CGAS)
· Assess the changes in multiple domains of cognitive functioning associated with treatment with paliperidone ER as assessed by the modified Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) assessment battery
· Assess the effect on sleep associated with treatment with paliperidone ER as measured by the sleep Visual Analog Scale (VAS) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Male or female between 12 and 17 years of age, inclusive. (Subject may become 18 years of age during the study but should be 17 years of age at the time of signing the informed consent)
• Subject must give assent to participate before screening procedures begin
• Parent(s) or the legal guardian(s) of the subject must sign an informed consent document indicating that they understand the purpose of and the procedures required for the study and give permission for their child’s participation in the study before screening procedures begin
• Subjects must not be a danger to themselves or others, and must have family support available to be maintained as outpatients. The K-SADS-PL diagnostic interview: item a), recurrent thoughts of death; item b), suicidal thoughts; item c), suicide attempts and their seriousness; item d), suicide attempts and their lethality; and item e) self-harming behavior must have a score of ≤2 for each item.
• Weight ≥29 Kg
• Female subjects must either:
– be incapable of pregnancy because of hysterectomy or tubal ligation.
– if heterosexually active and capable of pregnancy, have been using an acceptable method of contraception (hormonal contraceptives, intrauterine device, spermicide and barrier or double barrier methods) for at least 1 month before study entry and agree to continue the use of one of these contraception methods for the duration of the study.
– if sexually abstinent and capable of pregnancy, agree to continue abstinence or to use an acceptable method of birth control (either hormonal contraceptives, intrauterine device, spermicide and barrier or double barrier method) should sexual activity commence.
• A responsible adult must be available to accompany the subject to the investigational site at each visit, to provide reliable information for all study related evaluations, and to accurately and reliably dispense the study drug as directed
• Subjects must agree to be hospitalized at any time during the study, if it is deemed clinically necessary by the investigator.
• Subjects must be able to meet study requirements. If a subject is unable to read study information, study personnel may read the questions to the subject and mark his or her choices
• Subjects must meet the DSM-IV criteria for schizophrenia for at least one year. The K-SADS-PL questionnaire will be used to establish the diagnosis (including all supplements). Subjects should have had at least one adequate treatment with an antipsychotic before participation in this study.
• Parent(s) or the legal guardian(s) of the subject must have signed the informed consent form for DNA research indicating consent or refusal to participate in the DNA component of the study (where local regulations permit). Participation in this component is not required for participation in the main study
• Subjects must be otherwise physically healthy on the basis of a physical examination, medical history, ECG, and the results of clinical laboratory tests carried out within 21 days before baseline. |
|
| E.4 | Principal exclusion criteria |
· Subjects who, at screening, meet the DSM-IV criteria for dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance-induced psychotic disorder. Other comorbid disorders e.g., attention-deficit hyperactivity disorder (ADHD) are allowed, as long as the diagnosis of schizophrenia is the primary diagnosis and the comorbid disorders in the investigator’s judgment do not require medications (See Section 8, Concomitant Therapy)
· Subjects with mild, moderate, or severe mental retardation (i.e., documented intelligence quotient [IQ] <70), established by previous IQ testing or history
· Subjects with a known or suspected history of substance dependence (including alcohol, but excluding nicotine and caffeine) according to the DSM-IV criteria in the 3 months preceding screening.
· History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death in association with the use of drugs that prolong the QTc interval, including:
– heart rate of <50 bpm for subjects between 13 to 17 years of age, inclusive, and heart rate <55 bpm for subjects less than 13 year of age.
– demonstration of repeated prolonged QTc Fridericia interval >450 msec, as measured on more than one ECG (either during screening, or from a previous medical record).
– the following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure, polymorphic ventricular tachycardia
– clinically relevant hypocalcemia, hypokalemia, or hypomagnesemia
· Concomitant use of drugs that prolong the QTc interval (including Class A [e.g., quinidine, procainamide] or Class III [e.g., amiodarone, sotalol] antiarrhythmic medications); presence of congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell, and Lange-Nielsen syndrome)
· Female subjects who are pregnant (as confirmed by urine pregnancy test performed at screening or baseline), planning to become pregnant or are nursing
• Subjects with a known or suspected history of seizure disorder, including
neuroleptic malignant syndrome, encephalopathic syndrome, tardive
dyskinesia, or insulin dependent diabetes mellitus
• Presence of any significant or unstable cardiovascular, respiratory, renal,
hepatic, hematologic, endocrine, immunologic, or other systemic disease
• Have active and clinically relevant hypo- or hyperthyroidism unless
stabilized on appropriate medications for at least 3 months
• History of severe preexisting gastrointestinal narrowing (pathologic or
iatrogenic) or an inability to swallow oral study drug with the aid of water
• Subjects who, in the opinion of the investigator, should not discontinue or
participate in washout of prohibited concomitant psychotropic
medications (Section 8, Concomitant Therapy)
• Subjects who have received electroconvulsive therapy in the 3 months
preceding baseline
• Subjects who, despite washout, continue to use any prohibited
concomitant medication, substance of abuse, or alcohol within 5 half-lives
(up to a maximum of 5 days) before baseline, as evidenced by history or
as suggested by a positive urine drug screen at baseline
• Subjects who have received clozapine in the 2 months before the baseline
visit.
• Subjects who have received a depot antipsychotic within 2 treatment
cycles before the baseline visit
• Clinically significant abnormalities in medical history, physical
examination, ECG or biochemistry, hematology, or urinalysis results.
Evidence of clinically significant hepatic disease [aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the
upper limit of normal] at screening
• Known or suspected hypersensitivity or intolerance to risperidone or
paliperidone
• Subjects who have participated in any investigational drug study
(including risperidone or paliperidone) in the 30 days preceding screening
or who have participated in 2 or more clinical trials in the past year, with
the exception of R076477PSZ3001
• Children of employees of the investigator or study center, when the
employee has direct involvement in the proposed study or other studies
under the direction of that investigator or study center
• Subjects within their first psychotic episode.
• History of any active malignancy (with the exception of excised basal cell
carcinoma) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PANSS rating from baseline to end of trial |
|
| 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 | 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 | No |
| 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 | No |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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