| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Binge eating disorder is characterized by recurrent, distressing episodes of uncontrolled consumption of large amounts of food (binge eating) without the inappropriate compensatory weight loss behaviors of bulimia nervosa. In May 2013, BED was formally added as a free standing diagnosis under DSM-5. |
| Trastorno de la alimentación se caracteriza por atracones recurrentes, episodios angustiosos de consumo descontrolado de grandes cantidades de alimentos (atracones) sin las conductas compensatorias inapropiadas de pérdida de peso de la bulimia nerviosa. En mayo de 2013, BED se añadió formalmente como un diagnóstico independiente gratis como DSM-5 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Binge eating disorder |
| Trastorno por atracón |
|
| 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 |
To evaluate maintenance of efficacy based on time to relapse between SPD489 (50 or 70mg) and placebo, as measured by the number of binge days (defined as days during which at least 1 binge episode occurs) per week as assessed by clinical interview based on subject diary and Clinical Global Impression ? Severity (CGI-S) scores for patients who responded to SPD489 by the end of the Open-label Treatment Phase.
(Relapse is defined as subject reports with at least 2 or more binge days each week for 2 consecutive weeks [14 days] prior to the visit and have a at least 2 or more point increase in CGI-S score relative to their score at the Randomized-withdrawal Baseline Visit.) |
| Evaluar el mantenimiento de la eficacia con SPD489 (50 o 70 mg) y placebo en función del tiempo hasta la recidiva. Se medirá según el número de días con episodios de atracón (definidos como días en los que ocurre al menos un episodio de atracón) a la semana, determinados mediante entrevista clínica basada en el diario del paciente y en las puntuaciones de la Impresión clínica global de la gravedad (Clinical Global Impression ? Severity, CGI-S) de los pacientes con respuesta al tratamiento con SPD489 al final de la fase de tratamiento abierto |
|
| E.2.2 | Secondary objectives of the trial |
1 To evaluate the efficacy of SPD489 as compared to placebo at Visit 21 on the number of binge-eating days per week as assessed by clinical interview based on subject diary
2 To evaluate the efficacy of SPD489 as compared to placebo at Visit 21 on the global clinical measure of severity as measured by the CGI-S scale
3 To evaluate the efficacy of SPD489 as compared to placebo at Visit 21 on the obsessive/compulsive binge eating symptoms as measured by the Y-BOCS-BE
4 To evaluate the impact of SPD489 on a measure of the perception of health and quality of life for appraisal of clinical and economic health status as assessed by EQ5D5L.
5 To evaluate the safety and tolerability of SPD489 based on the occurrence of TEAEs, vitals signs results (including weight and waist circumference), clinical laboratory results, ECG results, and the C-SSRS results .
6 To evaluate amphetamine withdrawal symptoms as measured by the ACSA in the Follow up Phase. |
Evaluar eficacia SPD489 comparada con placebo en visita 21 (semana 38) en nº de días con episodios atracón/semana según entrevista clínica basada en diario paciente.
Evaluar eficacia SPD489 comparada con placebo en visita 21 (semana 38) en la medida clínica global de la gravedad según la escala CGI-S.
Evaluar la eficacia de SPD489 comparada con placebo en visita 21 (semana 38) en los síntomas de atracón obsesivos/compulsivos, según escala de obsesiones y compulsiones de Y-BOCS-BE
4.Evaluar impacto d SPD489 en indicador d percepción d salud y d calidad vida para valoración d estado de salud según cuest EQ-5D-5L
Evaluar seguridad tolerabilidad SPD489 basada en incidencia d AA aparecidos durante el tto (AAT), los valores de las cts vitales (inc peso/perímetro abdominal), resultados de análisis, resultados d ECG y resultados para evaluar C-SSRS, en fases tto.abierto y retirada aleatoria en doble ciego
Evaluar síntomas d retirada d anfetaminas, en fase seguimiento con escala ACSA |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The subject cannot be enrolled in the study before all of the following inclusion criteria (including test results) are met:
- Subject is between 18-55 years of age (or age of majority if greater
than 18 years of age, as defined by local regulations), inclusive, at the
time of consent.
- Subject meets DSM-IV-TR criteria for a diagnosis of BED.
- Subject's BED is of at least moderate severity with subjects reporting
at least 3 binge eating days per week for the 14 days prior to the
Baseline Visit (Visit 0) as documented in the subject's binge diary. A
binge day is a day during which at least 1 binge eating episode occurs.
- Subject must have a CGI-S score superior or equal to 4 at the
Screening Visit (Visit -1) and Baseline Visit (Visit 0).
- Subject has a BMI of superior or equal to 18 and inferior or equal to 45
at the Screening Visit (Visit -1) and the Baseline Visit (Visit 0).
- Subject is able to provide written, personally signed, and dated
informed consent to participate in the study before completing any
study-related procedures.
- Subject is willing and has an understanding and ability to fully comply
with study procedures and restrictions defined in this protocol. |
El sujetó no será incluido en el estudio si no cumple todos los criterios que indican a continuación (incluyendo el resultado de los test)
_Paciente que tenga entre 18 (o, si las leyes locales fijan la mayoría de edad en una edad superior, la edad a la que se alcance la mayoría) y 55 años de edad, ambos inclusive, en el momento del consentimiento
-Paciente que cumpla los criterios siguientes del Manual diagnóstico y estadístico de los trastornos por atracón
-Paciente con TPA moderado o grave que refiera al menos tres días con episodios de atracón a la semana durante los 14 días previos a la visita de basal en abierto (visita 0), documentados en el diario de atracones del paciente. Un día con episodios de atracón es un día en el cual aparece al menos un episodio de atracón
- Paciente con una puntuación en la escala CGI-S 4 en la visita de selección (visita -1) y en la visita basal en abierto (visita 0).
-Paciente con índice de masa corporal (IMC) ? 18 y ? 45 en la visita de selección (visita -1) y en la visita basal en abierto (visita 0)
-Paciente capaz de proporcionar el consentimiento informado (por escrito, firmado personalmente y fechado) para participar en el estudio antes de realizar cualquier procedimiento relacionado con él.
-Paciente que quiera y pueda comprender y cumplir completamente los procedimientos y restricciones definidos en este protocolo |
|
| E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following exclusion
criteria are met:
? Subject has current diagnosis of bulimia nervosa or anorexia nervosa
as defined by the SCID-I eating disorders module.
? Subject is receiving psychotherapy (eg, supportive psychotherapy,
cognitive behavior therapy, interpersonal therapy) or weight loss
support (eg, Weight Watchers) for BED that began within the 3 months
prior to the Screening Visit (Visit -1). Subjects who are receiving
psychotherapy or weight loss support that was initiated >=3 months
prior to the Screening Visit (Visit -1) will be allowed to continue to
receive psychotherapy or weight loss support during the study only if
they agree to not make any changes in the frequency or nature of their
psychotherapy or weight loss support during the course of this study.
? Subject has a current comorbid Axis I or Axis II psychiatric disorder
that is either controlled with medications prohibited in this study or is
uncontrolled and associated with significant symptoms (note: subjects
with mild mood or anxiety symptoms that do not meet criteria for Axis I
disorder, do not require treatment based on the investigator's
assessment, and do not confound efficacy or safety assessments in the
opinion of the examining investigator may be included).
? Subject has a lifetime history of psychosis, mania, hypomania,
dementia, or ADHD.
? Subject is considered a suicide risk in the opinion of the investigator,
has previously made a suicide attempt, or is currently demonstrating
active suicidal ideation. Subjects with intermittent passive suicidal
ideation are not necessarily excluded based on the assessment of the
investigator.
? Subject has a recent history (within the past 6 months) of suspected
substance abuse or dependence disorder in accordance with DSM-IV-TR
criteria. Subjects with a lifetime history of amphetamine, cocaine, or
other stimulant abuse and/or dependence will be excluded. Nicotine
dependence is not exclusionary.
? Subject has a concurrent chronic or acute illness (such as severe
allergic rhinitis, an infectious process requiring antibiotics, or diabetes),
disability, or other condition that might confound the results of safety
assessments administered in the study or that might increase risk to the
subject. Subject will be excluded if he or she has any additional
condition(s) that in the investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the
subject to participate in the study. This would include any significant
illness or unstable medical condition that could lead to difficulty in
complying with the protocol. Mild, stable asthma is not exclusionary.
? Subject has known history of symptomatic cardiovascular disease,
advanced arteriosclerosis, structural cardiac abnormality,
cardiomyopathy, serious heart rhythm abnormalities, coronary artery
disease, or other serious cardiac problems that may place them at
increased vulnerability to the sympathomimetic effects of a stimulant
medication.
? Subject has a known family history of sudden cardiac death or
ventricular arrhythmia.
? Subject has any clinically significant ECG prior to the Baseline Visit
(Visit 0).
? Subject has any clinically significant laboratory abnormality prior to
the Baseline Visit (Visit 0). Subjects with hypokalemia at the Screening
Visit or prior to the Baseline Visit (Visit 0) will be excluded.
? Subject has a history of moderate or severe hypertension or has a
resting average (of 3 readings) sitting systolic blood pressure
>139mmHg or an average (of 3 readings) diastolic blood pressure
>89mmHg at the Screening Visit (Visit -1) and/or Baseline Visit (Visit
0). NOTE: Subjects with mild (Stage 1), well-controlled hypertension on
a stable antihypertensive treatment regimen, defined as having
maintained the current dose for a period of at least 3 months or longer
at the time of the Screening Visit (Visit -1), are allowed. |
Los sujetos serán excluidos del estudio si no cumple alguno de estos criterios:
-Paciente con diagnóstico actual de bulimia nerviosa o anorexia nerviosa según la definición del módulo de trastornos de la conducta alimentaria de la SCID-I.
-Paciente que recibe psicoterapia (p. ej., psicoterapia de soporte, psicoterapia cognitivo-conductual, terapia interpersonal) o ayuda para perder peso (p. ej., Weight Watchers) para el TPA, que se inició en los tres meses previos a la visita de selección (visita -1). A los pacientes que reciben psicoterapia o ayuda para perder peso iniciada ? 3 meses antes a la visita de selección (visita -1) se les permitirá continuar recibiéndola durante el estudio solo si aceptan no realizar ningún cambio en su frecuencia o naturaleza durante el transcurso del estudio
-Paciente con un trastorno psiquiátrico del Eje I o del Eje II concomitante actual controlado con medicamentos prohibidos en este estudio o no controlado y que se asocia a síntomas significativos (atención: se puede incluir a pacientes con síntomas leves de trastorno del estado de ánimo o ansiedad que no cumplan los criterios para trastornos del Eje I, que no requieran tratamiento según la evaluación del investigador y que no interfieran en las evaluaciones de la eficacia o la seguridad según la opinión del investigador).
-Paciente con antecedentes de psicosis, manía, hipomanía, demencia o TDAH
-Paciente con riesgo de suicidio, según el criterio del investigador, que haya intentado suicidarse anteriormente o que muestre actualmente ideas de suicidio activas. No es necesario excluir a los pacientes con ideas de suicidio intermitentes, en opinión del investigador.
-Paciente con antecedentes recientes (en los últimos seis meses) de sospecha de abuso de sustancias o trastorno por dependencia según los criterios del DSM-IV-TR. Se excluirá a los pacientes con antecedentes de abuso y /o dependencia de anfetaminas, cocaína u otros estimulantes. La dependencia de la nicotina no se considera motivo de exclusión
-Paciente que padece una enfermedad crónica o aguda concomitante (como rinitis alérgica intensa, un proceso infeccioso que requiera la administración de antibióticos o diabetes), discapacidad u otros trastornos que puedan interferir en los resultados de las evaluaciones de seguridad del estudio o que pudieran aumentar el riesgo del paciente. Se excluirá al paciente si presenta algún trastorno adicional que, en opinión del investigador, pueda impedir que el paciente complete el estudio o que haga que la participación en el estudio no sea lo mejor para él. Esto incluye cualquier enfermedad significativa o proceso patológico inestable que pueda dificultar el cumplimiento del protocolo. El asma leve estable no se considera motivo de exclusión
-Paciente con antecedentes conocidos de enfermedad cardiovascular sintomática, arterioesclerosis avanzada, anomalías cardíacas estructurales, miocardiopatía, anomalías graves del ritmo cardíaco, arteriopatía coronaria u otros problemas cardíacos graves que puedan aumentar la vulnerabilidad a los efectos simpaticomiméticos de la medicación estimulante
-Paciente con antecedentes familiares conocidos de muerte cardíaca súbita o arritmia ventricular
-Paciente con algún ECG clínicamente significativo previo a la visita basal en abierto (visita 0).
-Paciente con alguna anomalía analítica clínicamente significativa antes de la visita basal en abierto (visita 0). Se excluirá a los pacientes con hipopotasemia durante la visita de selección (visita -1) o antes de la visita basal en abierto (visita 0)
-Paciente con antecedentes de hipertensión moderada o grave, o que presenta una presión arterial sistólica media (de tres lecturas) en sedestación y en reposo > 139 mm Hg o una presión arterial diastólica media (de tres lecturas) > 89 mm Hg en la visita de selección (visita -1) y/o en la visita basal en abierto (visita 0). Atención: se permite la inclusión de pacientes con hipertensión leve bien controlada (estadio 1) con una pauta de tratamiento antihipertensor estable, definido como el mantenimiento de la dosis actual durante un periodo de al menos tres meses o más en el momento de la visita de selección (visita -1) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to relapse from randomization (Visit 8). The time of relapse is defined as the visit date when the relapse is confirmed. |
| Tiempo hasta la recaída a partir de la aleatorizacion (visita 8). El momento de la recaída se define como la fecha de visita cuando se confirma la recaída |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Subject Daily Diary Visit 8 - Visit 21 |
| Diario del paciente Visita 8- Visita 21 |
|
| E.5.2 | Secondary end point(s) |
1. Change from Visit 8 (Week 12) to Visit 21 (Week 38) in the number of binge days per week
2. CGI-S at Visit 21/ET (Week 38)
3. Change from Visit 8 (Week 12) to Visit 21 (Week 38) in Y-BOCS-BE |
?Cambio desde la visita 8 (semana 12) hasta la visita 21 (semana 38) en el número de días con episodios de atracón a la semana
?CGI-S en la visita 21 (semana 38)
?Cambio desde la visita 8 (semana 12) hasta la visita 21 (semana 38) en la puntuación de la escala Y-BOCS-BE |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Subject Daily Diary Visit 8 - Visit 21
2. CGI-S: Visit 21/ET
3. Y-BOCS-BE: Visit 8 and Visit 21 |
1. Diario del paciente Visit 8 - Visit 21
2. CGI-S: Visita 21/ET
3. Y-BOCS-BE: Visita 8 and Visit 21 |
|
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Open-label, Dose Optimization followed by randomisation based on response |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 |
|
| 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
|
| The end of the trial is signified by the last patient finishing the last visit (the Follow-up Visit) of the trial. |
| El fin del ensayo se considera cuando el ultimo paciente realiza la ultima visita (visita de seguimiento) del ensayo |
|
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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