E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Schizophrenia |
Esquizofrenia |
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E.1.1.1 | Medical condition in easily understood language |
Schizophrenia |
Esquizofrenia |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | 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 open-label study is to continue to provide aripiprazole IM Depot treatment (400 mg or 300 mg) to subjects with schizophrenia who completed the 52-week, open-label safety and tolerability Study 248. Subjects can receive this therapy until aripiprazole IM Depot is commercially available in any dosage [including generic formulation(s)] in the country where the study is being conducted, the commercial availability of aripiprazole IM Depot is terminated by the sponsor, or until the study end date of 31 Dec 2018 is reached. |
El objetivo principal de este estudio abierto es continuar proporcionando el tratamiento con aripiprazolintramuscular (IM) de liberación retardada (400 mg o 300 mg) a sujetos con esquizofrenia que han completado el Estudio 31 08 248 abierto, de seguridad y tolerabilidad, de 52 semanas (en adelante llamado Estudio 248). Los sujetos pueden recibir este tratamiento hasta que el aripiprazol IM de liberación retardada esté comercializado en cualquier dosis (incluidas las formulaciones genéricas) en el país en el que se esté realizando el estudio o hasta que se alcance la fecha de finalización del estudio el 31 de diciembre de 2018. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to collect long-term safety data on aripiprazole IM Depot in addition to what was collected in Study 248 (52-weeks). |
El objetivo secundario es recopilar datos de seguridad a largo plazo sobre aripiprazol IM de liberación retardada, adicionales a los recogidos en el Estudio 248 (52 semanas). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with a current diagnosis of schizophrenia, as defined by DSM-IV-TR criteria, who completed the open-label extension Study 248 (completed Study 248 study completion visit, Week 52) 2. Subjects who, in the investigator's judgement, may benefit from continued participation in an aripiprazole IM Depot study. 3. The baseline visit for Study 270 (which is the Week 52 visit of Study 248) and the first injection for Study 270 must occur within 4 weeks (which is defined as 28 [-2/+10] days) of the last injection in Study 248. 4. Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by IRB/IEC), prior to the initiation of any protocol-required procedures. 5. Subjects able to understand the nature of the study and follow protocol requirements and who can read and understand the written word in order to complete patient-reported outcomes measures. 6. Outpatient status. |
1-Sujetos con un diagnóstico actual de esquizofrenia, definida según los criterios del DSM-IV-TR, que hayan completado el estudio abierto de extensión Estudio 248 (visita de finalización del estudio del Estudio 248 completada, Semana 52). 2-Sujetos que, a juicio del investigador, se pueden beneficiar de continuar participando en un estudio del aripiprazol IM de liberación retardada. 3-La visita inicial para el Estudio 270 (que coincide con la visita de la Semana 52 del Estudio 248) y la primera inyección del Estudio 270 deben realizarse dentro de las 4 semanas(que se define como 28 [-2/+10] días) posteriores a la última inyección del Estudio 248. 4-Sujetos que sean capaces de proporcionar un consentimiento informado por escrito y/o el consentimiento de un representante legalmente aceptable (como requiere la JIR/CEIC) antes del inicio de cualquier procedimiento exigido por el protocolo. 5-Sujetos capaces de entender la naturaleza del estudio y de seguir los requisitos del protocolo, y que sepan leer y entender la lengua escrita para poder completar las medidas de resultados referidas por el paciente. 6-Paciente ambulatorio. |
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E.4 | Principal exclusion criteria |
SEX AND REPRODUCTIVE STATUS 1. Sexually active males who are not practising double-barrier birth control or who will not remain abstinent during the study and for 180 days following the last dose of study medication, or sexually active females of childbearing potential who are not practising double-barrier birth control or who will not remain abstinent during the study and for 150 days following the last dose of study medication. If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), birth control pill, birth control implant, condom, or sponge with spermicide. 2. Females who have a positive serum pregnancy test result at study entry. TARGET DISEASE 3. Subjects with a current DSM-IV-TR diagnosis other than schizophrenia including schizoaffective disorder, MDD, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. MEDICAL HISTORY AND CONCURRENT DISEASE 4. Subjects with a significant risk of violent behaviour or a significant risk of committing suicide based on the investigator's judgement. 5. Subjects who currently meet DSM-IV-TR criteria for substance dependence; including alcohol and benzodiazepines, but excluding caffeine and nicotine. 6. Subjects who have a history or evidence of a medical condition that would expose them to an undue risk of a significant AE or interfere with assessments of safety or efficacy during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as determined by the clinical judgement of the investigator. 7. Subjects with epilepsy or a history of seizures, except for a single childhood febrile seizure, post traumatic, alcohol withdrawal, etc. PHYSICAL AND LABORATORY TEST FINDINGS 8. Any subject with a positive drug screen for cocaine or other drugs of abuse (excluding marijuana, stimulants, and other prescribed medications). 9. The following laboratory test, vital sign, ECG results are exclusionary: a) platelets =<75,000/mm3 b) Hemoglobin =<9 g/dL c) Neutrophils, absolute =<1000/mm3 d) Aspartate transaminase (AST) > 3x upper limit of normal e) Alanine transanimase (ALT) > 3x upper limit of normal f) Creatinine >=2 mg/dL g) Diastolic blood pressure > 105 mm Hg h) At baseline, QTc > 475 msec on either the QTcB (Bazett) or QTcF (Fridericia) corrections on 2 of 3 time points of triplicate ECGs performed (refer to NOTE in protocol) ALLERGIES AND ADVERSE DRUG REACTIONS 10. Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones. 11. Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia at screening. PROHIBITED THERAPIES AND/OR MEDICATIONS 12. Subjects likely to require prohibited concomitant therapy during the trial (see table in protocol) 13. Subjects who may require cytochrome P450 (CYP) 2D6 or CYP3A4 inhibitors or CYP3A4 inducers during the trial (see table in protocol). 14. Any subject who requires or may need any other antipsychotic medications during the course of the study. OTHER EXCLUSION CRITERIA 15. Prisoners or subjects who are compulsorily detained (involuntary incarcerated) for any reason must not be enrolled into this trial. 16. Electroconvulsive therapy within 180 days prior to entry. 17. Aripiprazole IM Depot (including generic formulation) is commercially available in the subject's country. |
Sexo y estado reproductivo 1-Hombres sexualmente activos que no utilicen un método anticonceptivo de doble barrera o que no se vayan a mantener en abstinencia durante el estudio y durante los 180 días posteriores a la última dosis de la medicación del estudio, o mujeres sexualmente activas con posibilidad de procrear que no utilicen un método anticonceptivo de doble barrera o que no se vayan a mantener en abstinencia durante el estudio y durante los 150 días posteriores a la última dosis de la medicación del estudio. 2-Mujeres con resultado positivo en la prueba de embarazo en sangre en el momento de incorporación al estudio.(*) Enfermedad diana 3-Sujetos con un diagnóstico actual según el DSM-IV-TR diferente a la esquizofrenia(*) 4-Sujetos con riesgo significativo de comportamiento violento o riesgo significativo de suicidio a juicio del investigador. 5-Sujetos que actualmente cumplen los criterios del DSM-IV-TR de dependencia de alguna sustancia(*) 6-Sujetos con antecedentes o evidencias de alguna patología que les exponga a un riesgo excesivo de padecer AA significativos o que pueda interferir con las evaluaciones de seguridad o eficacia durante el transcurso del ensayo(*) 7-Sujetos con epilepsia o antecedentes de convulsiones(*) Hallazgos físicos y de pruebas de laboratorio 8-Cualquier sujeto con una prueba de detección de drogas positiva para cocaína u otras sustancias de abuso(*) 9-Los siguientes resultados de pruebas de laboratorio, constantes vitales y ECG son excluyentes:Plaquetas ? 75.000/mm3, Hemoglobina ? 9 g/dl, Neutrófilos totales ? 1.000/mm3, AST y ALT> 3 veces el límite superior de la normalidad,Creatinina ? 2 mg/dl, Tensión arterial diastólica > 105 mmHg,Al inicio, QTc > 475 ms en la corrección QTcB (Bazett) o QTcF (Fridericia) en 2 de 3 puntos de los EGC realizados por triplicado(*) Alergias y reacciones adversas a medicamentos 10-Sujetos alérgicos, intolerantes o que no respondan al tratamiento previo con aripiprazol u otras quinolinonas. 11-Sujetos con antecedentes de síndrome neuroléptico maligno o discinesia tardía clínicamente significativa en la selección. Tratamientos y/o medicamentos prohibidos 12-Sujetos que probablemente requieran un tratamiento concomitante prohibido durante el ensayo(*) 13-Sujetos que puedan requerir inhibidores del citocromo P450 (CYP) 2D6 o CYP3A4 o inductores del CYP3A4 durante el ensayo(*) 14-Cualquier sujeto que requiera o pueda necesitar cualquier otra medicación antipsicótica durante el transcurso del estudio.(*) Otros criterios de exclusión 15-No deben incluirse en este ensayo a presos o sujetos detenidos forzosamente por cualquier motivo.(*) 16-Terapia electroconvulsiva en los 180 días previos al inicio. 17-El aripiprazol IM de liberación retardada (incluida la formulación genérica) está comercializado en el país del sujeto. (*) Ver más información en el protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
AEs will be examined by frequency, severity, seriousness, and discontinuation due to AEs. The Columbia Suicide Severity Rating Scale (C-SSRS) will be completed at baseline and every month to assess the risk of suicide events and to classify reported suicide events. Injection site pain will be evaluated by mean VAS scores as reported by the subject once every 6 months before and after injection. Extrapyramidal symptoms will be evaluated by calculating mean change from baseline in AIMS, SAS, and BARS every 6 months (more frequently if warranted). The investigator rating of localized pain, redness, induration, and swelling at the injection site will also be tabulated every 6 months. Vital signs will be assessed every 3 months and clinical laboratory tests, ECG, and physical examinations will be assessed every 12 months. |
Los AA se investigarán por frecuencia, intensidad, gravedad e interrupción del tratamiento debido a los AA. La escala de Columbia de valoración de la gravedad de la ideación suicida (C-SSRS) se valorará al inicio y después una vez al mes, para valorar el riesgo de actos suicidas y para clasificar los actos suicidas registrados. El dolor en el punto de inyección se evaluará una vez cada 6 meses antes y después de la inyección, mediante las puntuaciones medias de la EVA con los datos aportados por el paciente. Los síntomas extrapiramidales se evaluarán cada 6 meses calculando el cambio medio desde el inicio en las escalas AIMS, SAS y BARS.La valoración por parte del investigador del dolor, enrojecimiento, induración e hinchazón localizados en el punto de inyección también se realizará cada 6 meses. Las constantes vitales se evaluarán cada 3 meses y las pruebas clínicas de laboratorio, el ECG y el examen físico se evaluarán cada 12 meses. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Refer to E.5.1 |
Ver sección E.5.1 |
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E.5.2 | Secondary end point(s) |
CGI- S will be evaluated by calculating mean change from baseline every 3 months over the course of the study. |
La CGI-S se evaluará cada 3 meses durante el transcurso del estudio, calculando el cambio medio desde el inicio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Refer to E.5.2 |
Ver sección E.5.2 |
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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 | No |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 | No |
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 |
Argentina |
Australia |
Austria |
Bulgaria |
Chile |
Estonia |
Finland |
France |
Hungary |
India |
Korea, Republic of |
Malaysia |
Mexico |
Philippines |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Taiwan |
Thailand |
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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The End of Trial Date is defined as the last Date of Contact or the Date of Final Contact Attempt from the Post-treatment Follow-up case report form (CRF) page for the last subject completing or withdrawing from the trial. |
La fecha de Final del ensayo se define como la última fecha de contacto o fecha del último intento de contacto que aparece en la página de seguimiento post-tratamiento del cuaderno de recogida de datos (CRD) del último sujeto que haya completado el ensayo o se haya retirado del mismo. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |