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, a mental illness with a number of symptoms, including disorganised thinking and speech, hearing or seeing things that are not there, suspiciousness and delusions (false beliefs) |
Esquizofrenia, una enfermedad mental con varios síntomas, incluido el pensamiento y el habla desorganizados, oír o ver cosas que no existen, desconfianza e ideas delirantes (creencias falsas) |
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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 | 20.0 |
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 efficacy objective is to demonstrate that injection cycles consisting of a single administration of PP6M (700 or 1000 mg eq.) are not less effective than 2 sequentially administered injections of PP3M (350 or 525 mg eq.) for the prevention of relapse in subjects with schizophrenia previously stabilized on corresponding doses of PP1M (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). |
•El objetivo principal de eficacia es demostrar que los ciclos de inyección consistentes en una sola administración de PP6M (700 o 1000 mg eq.) no son menos eficaces que dos inyecciones de PP3M (350 o 525 mg) administradas de forma secuencial en cuanto a la prevención de las recidivas en pacientes con esquizofrenia previamente estabilizados con la correspondiente dosis de PP1M (100 o 150 mg eq.) o PP3M (350 o 525 mg eq.). |
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E.2.2 | Secondary objectives of the trial |
To Evaluate the safety & tolerability of PP6M (700 or 1000 mg eq.) in subjects with schizophrenia who have switched from corresponding doses of PP1M (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). • PK profile of PP6M (700 or 1000 mg eq.) administered in the gluteal muscle in subjects with schizophrenia who have switched from corresponding doses of PP1M (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). • clinically assessed efficacy of PP6M (700 or 1000 mg eq.) v. PP3M (350 or 525 mg eq.) in maintaining symptom control, functioning personally and socially, and achieving or sustaining remission in subjects with schizophrenia who were previously stabilized on corresponding doses of PP1M (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). • subject-reported efficacy outcomes of PP6M (700 or 1000 mg eq.) or PP3M (350 or 525 mg eq.) compared with treatment with previous oral antipsychotics in terms of satisfaction with medication & with participation in social roles. |
•Evaluar la seguridad y la tolerabilidad de PP6M (700 o 1000 mg eq.) en pacientes con esquizofrenia que estaban recibiendo la dosis de PP1M (100 o 150 mg eq.) o PP3M (350 o 525 mg eq.).•Evaluar el perfil farmacocinético de PP6M (700 o 1000 mg eq.), administrado en el glúteo, en pacientes con esquizofrenia que estaban recibiendo la dosis de PP1M (100 o 150 mg eq.) o PP3M (350 o 525 mg eq.).•Evaluar la eficacia determinada clínicamente de PP6M (700 o 1000 mg eq.) en comparación con PP3M (350 o 525 mg eq.) en cuanto al mantenimiento del control sintomático, el funcionamiento personal y social y alcanzar o mantener la remisión en pacientes con esquizofrenia previamente estabilizados con la correspondiente dosis de PP1M (100 o 150 mg eq.) o PP3M (350 o 525 mg eq.).•Evaluar los resultados percibidos por los pacientes en cuanto a la eficacia de PP6M (700 o 1000 mg eq.) o PP3M (350 o 525 mg eq.) relativa a la satisfacción con el tratamiento y participación en el rol social. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each potential subject must satisfy all of the following criteria to be enrolled in the study: 1.Male or female subjects. 2.Must be 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) to 70 years of age, inclusive, at the time of informed consent. 3.Must meet the diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) for at least 6 months before screening. 4.Must be receiving treatment with paliperidone palmitate (as either the PP1M or PP3M formulation), or injectable risperidone, or any oral antipsychotic. a.If the treatment is paliperidone palmitate, then: 1) The dose strength must be PP1M as 100 or 150 mg eq. or PP3M as 350 or 525 mg eq. 2) The dose timing must fit the study schedule. The next injection must be due within 28 days of the first screening (or first rescreening) visit. b.If the treatment is injectable risperidone, then the dose strength must be 50 mg, the dosing cycle must be every 2 weeks, the efficacy and tolerability must have been established as adequate with the same strength and frequency for at least 3 injection cycles before screening, and the subject must have a preference for a longer-acting injectable medication. c.If the treatment is an oral antipsychotic, then the subject must have a valid reason to discontinue the previous treatment, such as problems with efficacy, safety, or tolerability, or preference for a long-acting injectable medication. 5.Must be able, in the opinion of the investigator, to discontinue any antipsychotic medication other than PP1M or PP3M during the Screening Phase. 6.Must have a full PANSS score of <70 points at screening.
Please refer to protocol for additional inclusion criteria |
Todos los posibles participantes deben cumplir todos los criterios siguientes para ser incluidos en el estudio: 1.Varones o mujeres. 2.Edad de 18 (o la edad legal de consentimiento en la jurisdicción en la que tenga lugar el estudio) a 70 años, ambos inclusive, el momento del consentimiento informado. 3.Cumplir los criterios diagnósticos de esquizofrenia de acuerdo a la quinta versión del Manual diagnóstico y estadístico de los trastornos mentales (DSM-5) desde al menos seis meses antes de la selección. 4.Estar recibiendo tratamiento con palmitato de paliperidona (formulación PP1M o PP3M), risperidona inyectable o un antipsicótico oral. a.Si el tratamiento es con palmitato de paliperidona: 1)La dosis farmacéutica debe ser de 100 o 150 mg eq. en el caso de PP1M y de 350 o 525 mg eq. en el caso de PP3M. 2)El momento de administración debe adecuarse al calendario del estudio. La siguiente inyección debe administrarse en los 28 días siguientes a la primera visita de selección (o de repetición de la selección). b.Si el tratamiento es con risperidona inyectable, la dosis farmacéutica debe ser de 50 mg, el intervalo de administración debe ser de dos semanas, tiene que haberse confirmado durante al menos tres ciclos de inyección antes de la selección que la eficacia y la tolerabilidad con esa dosis farmacéutica y esa frecuencia de administración son adecuadas y el paciente ha de preferir un medicamento inyectable de acción prolongada. c.Si el tratamiento es con un antipsicótico oral, el paciente debe tener un motivo válido para suspenderlo, como por ejemplo la presencia de problemas relativos a la eficacia, seguridad o tolerabilidad o la preferencia por un medicamento inyectable de acción prolongada. 5.Ser capaz, en opinión del investigador, de suspender el tratamiento con antipsicóticos distintos del PP1M o el PP3M durante la fase de selección. 6.Tener una puntuación total de la PANSS < 70 en la fase de selección.
Por favor refiérase al protocolo para los criterios de inclusión adicionales. |
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E.4 | Principal exclusion criteria |
Any potential subject who meets any of the following criteria will be excluded from participating in the study: 1.Must not be receiving any form of involuntary treatment, such as involuntary psychiatric hospitalization, parole-mandated treatment, or court-mandated treatment. 2.Must not have attempted suicide within 12 months before screening and must not be at imminent risk of suicide or violent behavior, as clinically assessed by the investigator at the time of screening. 3.Must not have a DSM-5 diagnosis of moderate to severe substance use disorder (except for nicotine and caffeine) within 6 months of screening; however, acute or intermittent substance use prior to screening is not exclusionary, depending upon the clinical judgment of the investigator. 4.Must not have a history of neuroleptic malignant syndrome or tardive dyskinesia. 5Must not have a history of intolerability or severe reactions to moderate or higher doses of antipsychotic medications and must not have any other factors that would, in the judgment of the investigator, indicate that treatment with moderate or higher doses of paliperidone palmitate would be intolerable or unsafe. 6. Must not have been treated with injectable formulations of neuroleptic drugs based on active ingredients other than risperidone or paliperidone (eg, haloperidol decanoate, fluphenazine decanoate, etc) during the 6 months before screening.
Please refer to protocol for additional exclusion criteria |
No podrán participar en el estudio los pacientes que cumplan alguno de los criterios siguientes: 1.Estar recibiendo de forma involuntaria algún tipo de tratamiento, como hospitalización psiquiátrica involuntaria, tratamiento obligado para conseguir la libertad condicional o tratamiento por mandato judicial. 2.Haber cometido intento de suicidio en los 12 meses previos a la selección o estar en riesgo inminente de suicidio o de conducta violenta según la valoración clínica efectuada por el investigador en el momento de la selección. 3.Tener un diagnóstico de trastorno por consumo de sustancias (excepto nicotina y cafeína) moderado o grave según el DSM-5 en los seis meses previos a la selección; sin embargo, el consumo intermitente de sustancias antes de la selección no es motivo de exclusión, dependiendo del criterio clínico del investigador. 4.Tener antecedentes de síndrome neuroléptico maligno o discinesia tardía. 5.Tener antecedentes de intolerancia o reacciones graves a dosis moderadas o altas de antipsicóticos u otros factores que, a criterio del investigador, indiquen que el tratamiento con dosis moderadas o altas de palmitato de paliperidona sería intolerable o peligroso. 6.Haber recibido tratamiento con formulaciones inyectables de neurolépticos con principios activos distintos de la risperidona o el palmitato de paliperidona (por ejemplo, decanoato de haloperidol, decanoato de flufenazina, etc.) durante los seis meses anteriores a la selección.
Por favor refiérase al protocolo para los criterios de exclusión adicionales. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Time to relapse during the Double-blind Phase. This noninferiority primary endpoint will be based on the difference in Kaplan-Meier 12-month estimate of survival (ie, percentage of subjects remaining relapse-free) between PP6M and PP3M. |
1. Tiempo de recaída durante la fase de doble ciego. Este criterio de valoración principal de ausencia de inferioridad entre PP6M y PP3M se basará en la diferencia de la estimación de Kaplan-Meier de la supervivencia (es decir, el porcentaje de pacientes que se mantienen sin recidiva) a los 12 meses. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time between participant randomization into the Double-Blind phase and the first documentation of a relapse event |
Tiempo entre la aleatorización del paciente en la fase doble ciego y la primera documentación de un evento de recaída |
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E.5.2 | Secondary end point(s) |
(1)the PANSS total score and subscale scores, (2)the Clinical Global Impression - Severity (CGI-S), and (3) the Personal and Social Performance (PSP) scale. (4)Additionally, the proportion of subjects during the Double blind Phase who meet criteria for symptomatic remission |
(1) la puntuación total y de las subescalas de PANSS (2) la Impresión Clínica Global - Gravedad (CGI-S), y (3) la escala de funcionaiento Personal y Social (PSP). (4) Además, la proporción de pacientes durante la fase doble ciego que cumplen los criterios de remisión sintomática. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1), (2) and (3): changes from baseline during the ≥12 months of the Double-blind Phase (4): from the first 6 month time point to the end of the double blind phase |
(1), (2) y (3): cambios desde el momento basal durante los ≥12 meses de la Fase de doble ciego (4): desde el punto temporal de los seis primeros meses hasta el final de la fase de doble ciego |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Brazil |
Bulgaria |
Czech Republic |
France |
Germany |
Hong Kong |
Hungary |
India |
Italy |
Korea, Republic of |
Malaysia |
Mexico |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Taiwan |
Turkey |
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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LVLS |
Última visita del último paciente |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 2 |