E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
Trastorno Depresivo Mayor |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
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 evaluate the long-term safety and tolerability of SPD489 administered as a daily morning dose (20, 30, 50, and 70mg/day) as adjunctive therapy to an antidepressant for the treatment of major depressive disorder (MDD) in adults (18-65 years of age inclusive at the time of consent for the respective short-term antecedent SPD489 MDD study). Long-term safety will be described using: ? Occurrence of treatment-emergent adverse events (TEAEs), ? Responses to the Columbia Suicide Severity Rating Scale (C-SSRS), and ? Specific evaluation of blood pressure and pulse rate, clinical laboratory evaluations, and electrocardiogram (ECG) results. |
El objetivo principal es evaluar la tolerabilidad y seguridad a largo plazo del SPD489 administrado en dosis única por la mañana (20, 30, 50 y 70 mg/día), como tratamiento adyuvante a un antidepresivo para el tratamiento del TDM en adultos (18-65 años inclusive en el momento del consentimiento para el respectivo estudio a corto plazo precedente con SPD489 para el TDM). La seguridad a largo plazo se describe mediante: ?la aparición de AASDT; ? las respuestas a la escala Columbia para evaluar el riesgo de suicidio (C-SSRS); y ? la evaluación específica de la tensión arterial y el pulso, los análisis clínicos de laboratorio y los resultados del electrocardiograma (ECG). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of SPD489 on perception of health, quality of life, resource utilization, sexual functioning, depression symptoms, depression improvement, and amphetamine withdrawal symptoms. |
Evaluar los efectos de SDP489 SPD489 en lo que se refiere a la salud, la calidad de vida, utilización de recursos, el funcionamiento sexual, los síntomas de depresión, mejora la depresión y los síntomas de abstinencia de anfetamina. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Subject has completed 1 of the respective short-term antecedent SPD489 MDD studies and did not experience any clinically significant adverse events in the antecedent study that would preclude exposure to SPD489.
Subject was randomized as an inadequate responder in the antecedent study, or not randomized but continues to demonstrate residual depressive symptoms (MADRS total score of ?5) at the end of the antecedent study, and in the Investigator?s opinion has the potential to benefit from adjunctive pharmacologic treatment. |
El paciente ha completado uno de los estudios precedentes respectivos a corto plazo del SPD489 en el TDM y no experimentó ningún acontecimiento adverso (AA) clínicamente significativo en el estudio precedente que impida su exposición al SPD489.
El paciente fue aleatorizado como paciente que responde al tratamiento de manera inadecuada en el estudio precedente, o no fue aleatorizado, pero sigue exhibiendo síntomas residuales de depresión (puntuación total de ?5 en la escala de clasificación de la depresión de Montgomery-?sberg [MADRS]) al final del estudio precedente y, en opinión del investigador, tiene el potencial de beneficiarse de un tratamiento farmacológico adyuvante. |
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E.4 | Principal exclusion criteria |
Subject is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation.
Subject has any current co-morbid psychiatric disorder, either controlled with medications prohibited in this study or uncontrolled and associated with significant symptoms, which was not present or recognized at entry into the antecedent study and would have been exclusionary in the antecedent study.
A new onset or known history of serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant medication, a history of moderate to severe hypertension or an average (of 3 readings) resting sitting systolic blood pressure >139mmHg or an average (of 3 readings) diastolic blood pressure >89mmHg at study entry, or has a concurrent chronic or acute illness or unstable medical condition that may deteriorate that could confound the results of safety assessments, increase risk to the subject, or lead to difficulty complying with the protocol. |
El paciente se considera, en opinión del investigador, en riesgo de suicidio, y ha llevado a cabo un intento de suicidio en los últimos 3 años, o muestra actualmente pensamientos de suicido activos.
El paciente sufre actualmente cualquier trastorno psiquiátrico, ya sea controlado con medicamentos prohibidos en el presente estudio o bien no controlado y esté asociado con síntomas significativos, que no estaban presentes o reconocidos a la entrada en el estudio de antecedente y hubiera sido excluyente en el estudio antecedente. Una nueva aparición o antecedentes conocidos de problemas cardíacos graves que puedan poner al paciente en una mayor vulnerabilidad a los efectos simpaticomiméticos de un medicamento estimulante, una historia de hipertensión moderada a severa, o un promedio (de 3 lecturas) en reposo la presión arterial sistólica se sienta> 139mmHg o una promedio (de 3 lecturas) la presión arterial diastólica> 89mmHg al comienzo del estudio, o tiene una enfermedad crónica o aguda concurrente o condición médica inestable que puede deteriorarse que podrían confundir los resultados de las evaluaciones de seguridad, aumentar el riesgo de que el paciente, o dar lugar a dificultades para cumplir con el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability as assessed by the occurrence of treatment emergent adverse events (TEAEs), response to the Columbia-Suicide Severity Rating Scale (C-SSRS), and specific evaluation of blood pressure and pulse rate, clinical laboratory evaluations, and electrocardiogram (ECG) results. |
Evaluar la seguridad y tolerabilidad según las evaluaciones de las ocurrencia de eventos adversos emergentes del tratamiento (acontecimientos adversos), la respuesta a la Escala Columbia para evaluar el riesgo de suicidio (C-SSRS), y la evaluación específica de la presión arterial y el pulso, las evaluaciones clínicas de laboratorio y los resultados de los electrocardiogramas (ECG ). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
? TEAE: Week1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any, 53/Any ? C-SSRS: Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any, 53/Any ? BP and Pulse: Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any, 53/Any ? Clinical labs: Week 0, 24, and 52/Any ? ECG: Week 0, 12, 24, 36, 48, 52/Any |
- AASDT: Semana1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Otras, 53/Otras - escala Columbia para evaluar el riesgo de suicidio (C-SSRS): Semana 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Otras, 53/Otras - Tensión arterial y Pulso: Semana 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Otras, 53/Otras - Analíticas de laboratorio: Semana 0, 24, and 52/Otros - ECG: Semana 0, 12, 24, 36, 48, 52/Otras |
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E.5.2 | Secondary end point(s) |
1) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Sheehan Disabillity Scale (SDS) total score. 2) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Change in Clinical Global Impressions - Global Improvement (CGI-I) 3) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR) 4) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Short Form-12 Health Survey V2 (SF-12V2) 5) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L index score) 6) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (QLES-Q-SF) 7) Change from the Augmentation Baseline Visit of the antecedent study (Visit 8 [Week 8]) to Visit 16 (Week 52/Any) in the Changes in Sexual Functioning Questionnaire ? 14-item scale (CSFQ-14) 8) Change in the Patient Resource Utilization Questionnaire (PRUQ) 9) Amphetamine Cessation Symptom Assessment (ACSA) |
1)Cambio en la puntuación total Escala de discapacidad de Sheehan (EDS) desde la visita basal del tratamiento de potenciación (Visita 8 [Semana 8]) en el estudio precedente. 2)Cambio en la puntuación total en las impresiones globales de mejoría - mejoría global (ICG-MG) desde la visita basal del tratamiento de potenciación (Visita 8 [Semana 8]) del estudio precedente. 3) Cambio en el Inventario rápido de la sintomatología depresiva autoinforme (QIDS-SR) desde la visita inicial del tratamiento de potenciación (Visita 8 [Semana 8]) del estudio precedente. 4) Cambio desde la visita inicial del tratamiento de potenciación del estudio precedente (Visita 8 [Semana 8]) en la encuesta de salud SF-12 versión 2, forma breve (SF-12V2). 5) Cambio desde la visita inicial del tratamiento de potenciación del estudio precedente (Visita 8 [Semana 8]) en en el cuestionario de autoevaluación del grupo EuroQOL de 5 dimensiones y 5 niveles (EQ-5D-5L). 6) Cambio desde la visita inicial del tratamiento de potenciación del estudio precedente (Visita 8 [Semana 8]) en el Cuestionario de calidad de vida, satisfacción y placer, forma breve (Q LES-Q-SF). 7) Cambio desde la visita inicial del tratamiento de potenciación del estudio precedente (Visita 8 [Semana 8]) a la Visita 16 (Semana 52/Otras) el cuestionario de cambios en la función sexual, escala de 14 ítems (CSFQ-14) 8) Cambio en el cuestionario de utilización de recursos del paciente (Patient Resource Utilization Questionnaire (PRUQ) 9) Evaluación de los síntomas de abandono de las anfetaminas (ACSA) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any 2+3+6) Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any 4+5) Week: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Any 7+8) Week 0, 12, 24, 36, 48, 52/Any 9) Week: 53/Any |
1) Semana: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Otras 2+3+6) Semana 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Otras 4+5) Semana: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Otras 7+8) Semana 0, 12, 24, 36, 48, 52/Otras 9) Semana: 53/Otras |
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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 | 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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, amphetamine withdrawal |
Tolerabilidad y abstiencia a las anfetaminas |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Canada |
Chile |
Czech Republic |
Germany |
Hungary |
Mexico |
Poland |
Romania |
South Africa |
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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Last subject last visit |
Último Paciente, última visita |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |