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 | 12.1 |
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 is to explore the tolerability, safety and treatment response (maintained/improved efficacy), based on total Positive and Negative Syndrome Scale (PANSS) score, of a transition to flexibly dosed paliperidone palmitate in subjects with schizophrenia previously unsuccessfully treated with oral or long-acting injectable (LAI) antipsychotics. Subjects may present either acute or non-acute symptoms of schizophrenia. |
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E.2.2 | Secondary objectives of the trial |
To collect data in order to develop recommendations for use of and transition to paliperidone palmitate from previous oral and LAI antipsychotic medications. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Man or woman of minimally 18 years of age; •Subjects who meet the DSM-IV criteria for schizophrenia; •a) Subject is currently non-acute, i.e. on the same antipsychotic medication used for the treatment of schizophrenia given in an adequate dose and a CGI-S change less than or equal to 1 in the past 4 weeks before enrollment. Subject has been given an adequate dose of either an appropriate oral antipsychotic, or one of the following LAI antipsychotics: haloperidol decanoate, flupentixol decanoate, fluphenazine decanoate, zuclopenthixol or LAI risperidone, for an adequate period of time prior to enrollment, but current treatment is considered unsuccessful due to one or more of the following reasons: - lack of efficacy, or - lack of tolerability or safety, or - lack of compliance - patient’s wish
Lack of efficacy is defined as subjects with a baseline total PANSS score ≥ 70 or ≥ 2 items scoring ≥ 4 in the PANSS positive or negative subscale or ≥ 3 items scoring ≥ 4 in the PANSS general psychopathology subscale, as judged by the investigator.
Lack of tolerability is defined as the presence of clinically relevant (i.e., either clinically relevant according to the investigator and/or intolerable to the subject) side effects with the current antipsychotic medication.
OR
b) Subjects with acute symptoms of schizophrenia, previously treated with an oral antipsychotic, having a baseline total PANSS score ≥ 80 and a baseline CGI-S score ≥ 4; •The subjects may benefit from a switch of antipsychotic medication to paliperidone palmitate at the discretion of the investigator; •In the opinion of the investigator, subject is otherwise healthy on the basis of a physical examination, medical history and vital signs performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population; •Women must be: –postmenopausal for at least 1 year, or, –surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),or, –abstinent (at the discretion of the investigator/per local regulations), or, –if sexually active, be practicing a highly effective method of birth control (e.g, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel], male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. Prescription hormonal contraceptives (the “pill”) should not contain less than 20 micrograms of estrogen and should not be used as the only method of birth control. Women using oral contraceptives should agree to use an additional birth control method. •Women of childbearing potential must have a negative urine pregnancy test at screening; •Subjects must be willing and able to fill out self-administered questionnaires; •Willing/able to adhere to the prohibitions and restrictions specified in this protocol; •The subject is cooperative and reliable, and agrees to receive regular injections and complete all aspects of the protocol; •Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study; •Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug. |
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E.4 | Principal exclusion criteria |
•The subject’s psychiatric diagnosis is due to direct pharmacological effects of a substance (e.g., a drug of abuse or medication) or a general medical condition (e.g., clinically notable hypothyroidism); •First antipsychotic treatment ever i.e., subject has never been treated with antipsychotics before and antipsychotic treatment given in this study will be the first antipsychotic treatment that the subject will have ever received; •On clozapine during the last 3 months; •Subjects who remain at imminent risk of suicide even after clinical intervention; •Serious unstable medical condition, including recent and present clinically relevant laboratory abnormalities; •History or current symptoms of tardive dyskinesia; •History of neuroleptic malignant syndrome; •Subject received an investigational drug or used an investigational medical device within 3 months before the planned start of treatment, or has participated in more than one investigational drug trial in the past 12 months, or has planned use of other investigational drugs during the time frame of the trial, or is currently enrolled in an investigational study; •Pregnant or breast-feeding female; •Known allergies, hypersensitivity, or intolerance to risperidone or paliperidone or its excipients (refer to Section 14.1, Physical Description of Study Drug(s). All subjects without source documentation of previous risperidone or paliperidone exposure must undergo oral tolerability testing. Paliperidone ER will be administered for 2 days prior to Day 1 (Visit 2) to these subjects before the first injection of study drug. Only those subjects who demonstrate an ability to tolerate the drug as judged by the treating physician, will be eligible for treatment with paliperidone palmitate. •Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subjects from meeting or performing study requirements; •Subjects who have evidence of alcohol or drug dependence (except for nicotine and caffeine) according to DSM-IV Axis 1 criteria within 6 months prior to entry. However, subjects with current substance use or abuse, with the exception of intravenous drug use, will be eligible for enrolment; • Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Improved efficacy (≥20% improvement in total PANSS score at endpoint versus baseline) will be the primary endpoint for non-acute subjects transitioned from oral antipsychotics to paliperidone palmitate due to lack of efficacy of the previous oral antipsychotic treatment (Group A). Improved efficacy (≥30% improvement total PANSS score at endpoint versus baseline) will be the primary endpoint for acute subjects transitioned from oral antipsychotics to paliperidone palmitate (Group C). Maintained efficacy will be the primary endpoint for non-acute subjects transitioned to paliperidone palmitate due to lack of tolerability of or lack of compliance with the previous oral antipsychotic treatment (Group A) or due to patient’s wish. For the group of non-acute subjects switching from LAI antipsychotics (Group B), the primary objective is to descriptively explore tolerability, safety and treatment response (change versus baseline on total PANSS score) of switching from each individual LAI antipsychotic to paliperidone palmitate. |
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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 | Yes |
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 | 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
| 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 165 |
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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Last visit of the last patient in the last country in which paliperidone palmitate becomes available. The extension phase in an individual country will last until paliperidone palmitate becomes available or until a maximum duration of 12 months per subject, whichever comes first. As a consequence, the end of the study will at latest be 12 months after the completion of the 6-month core treatment phase of the last patient in the last country in which paliperidone palmitate becomes available. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 2 |