E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
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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 explore the efficacy, based on total Positive and Negative Syndrome Scale (PANSS) score, of flexibly dosed paliperidone ER in subjects with schizophrenia previously unsuccessfully treated with other oral antipsychotics. Unsuccessfully treated means that, despite the subject was treated with an adequate dose of an appropriate oral antipsychotic for an adequate period of time, this previous treatment is considered unsuccessful due to one or more of the following reasons: lack of efficacy, lack of tolerability, lack of compliance and/or other reasons. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: · To explore the tolerability and safety of a transition to flexibly dosed paliperidone ER in subjects with schizophrenia previously unsuccessfully treated with other oral antipsychotics; · To explore the characteristics of response within different subgroups of a transition from previous antipsychotic medication to flexibly dosed paliperidone ER. This will be done by assessing: · PANSS · proportion of subjects improving 20% or more in total PANSS from baseline to endpoint · CGI-S · PSP · SF 36 Health Survey · subject satisfaction; · sleep quality and daytime drowsiness · side effect profiles by means of ESRS, physical examination, body weight, vital signs and AEs
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Subject meets the DSM-IV criteria for schizophrenia; · Subject is previously non-acute, i.e. on the same antipsychotic medication used for the treatment of schizophrenia and CGI-S change of 1 or less in the past 4 weeks before enrollment. Subject has been given an adequate dose of an appropriate oral antipsychotic for an adequate period of time prior to enrollment, but previous treatment is considered unsuccessful due to one or more of the following reasons: lack of efficacy, lack of tolerability or safety, lack of compliance and/or other reasons to switch to another antipsychotic medication; · Male or female, aged ≥ 18 years; · Subject is able to read, understand and sign the Institutional Review Board-approved informed consent form; · Subject is healthy on the basis of a physical examination and vital signs at screening; · Female subjects must be postmenopausal for at least 1 year, surgically sterile, abstinent, or, if sexually active, agree to practice an effective method of birth control before entry and throughout the study. Effective methods of birth control include prescription hormonal contraceptives, contraceptive injections, intrauterine devices, double barrier method, contraceptive patch and male partner sterilization. Female subjects must also have a negative urine pregnancy test at screening; · Subjects must be willing and able to fill out self-administered questionnaires.
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E.4 | Principal exclusion criteria |
· On clozapine, any conventional depot neuroleptic or Risperdal CONSTA during the last 3 months; · Serious unstable medical condition including severe renal impairment, and/or known clinically relevant laboratory abnormalities including. clinically relevant abnormal values and ECG at screening; · History or current symptoms of tardive dyskinesia; · History of neuroleptic malignant syndrome; · Judged to be at high risk for adverse events, violence, or self-harm; · Pregnant or breast-feeding female; · Participation in an investigational drug trial in the 30 days prior to selection; · Known hypersensitivity to paliperidone ER or risperidone; · Inability to swallow the study medication whole with the aid of water (subjects may not chew, divide, dissolve, or crush the study medication, as this may affect the release profile); · Employees of the investigator or study center, persons with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or family members of the employees or the investigator; · Subjects with a current use or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria; . Subject under legal protection as defined by French Public Health Code; . History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including; · HR < 50 · Demonstration of repeated prolonged QTc Fridericia or Bazett interval > 450 msec, as measured on more than one ECG (either during screening, or from prior medical record) · the following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure, polymorphic ventricular tachycardia or history of cardiac arrhythmia · clinically relevant hypocalcemia, hypokalemia or hypomagnesemia; concomitant use of drugs that prolong the QTc interval (including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications) antipsychotic medications (e.g,chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval; . presence of congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell and Lange-Nielsen syndrome).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy criterion will be the change from baseline in total PANSS score at the end of the main study phase (Week 26 or last post-baseline visit). For the group of subjects that transitioned for the main reason of lack of efficacy, improved efficacy based on the percentage of patients with ≥ 20% improvement in total PANSS will be the primary parameter. For the group of subjects that transitioned for the main reason of lack of tolerability, lack of compliance or other reason, maintained efficacy based on the change in total PANSS, will be the primary parameter. |
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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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
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 |
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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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |