Clinical Trials Register

Summary
EudraCT Number:	2011-003018-17
Sponsor's Protocol Code Number:	SPD489-322
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-08-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2011-003018-17

A.3

Full title of the trial

The SPD489-322 Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination with an Antidepressant in the Treatment of Adults with Major Depressive Disorder with Inadequate Response to Prospective Treatment with an Antidepressant

Estudio SPD489-322 de fase 3, multicéntrico, aleatorizado, doble ciego, de
grupos paralelos y controlado con placebo, de ajuste de la dosis flexible, de
la eficacia y la seguridad de SPD489 en combinación con un antidepresivo
en el tratamiento de adultos con trastorno depresivo mayor con respuesta
inadecuada al tratamiento prospectivo con un antidepresivo

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to examine the study drug, SPD489, in people with major depressive disorder (MDD) who are taking certain types of antidepressants and continuing to have MDD symptoms.

Se trata de un ensayo para evaluar el fármaco del estudio, SPD489, en
personas que sufren Trastorno Depresivo Mayor (TDM) que están tomando
ciertos tipos de antidepresivos y que continúan teniendo síntomas de TDM.

A.3.2

Name or abbreviated title of the trial where available

SPD489-322

A.4.1

Sponsor's protocol code number

SPD489-322

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Shire Development LLC
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Shire Development LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Shire Pharmaceuticals Ltd
B.5.2	Functional name of contact point	Medical Communications
B.5.3	Address:
B.5.3.1	Street Address	Hampshire International Business Park
B.5.3.2	Town/ city	Chineham, Basingstoke, Hampshire
B.5.3.3	Post code	RG24 8EP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4408000556614
B.5.5	Fax number	+4401256894714
B.5.6	E-mail	medinfoglobal@shire.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vyvanse
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire US Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lisdexamfetamine dimesylate (LDX)
D.3.2	Product code	SPD489
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lisdexamfetamine dimesylate
D.3.9.1	CAS number	608137-33-3
D.3.9.2	Current sponsor code	SPD489
D.3.9.3	Other descriptive name	NRP104
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	70
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 4
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Major Depressive Disorder

Trastorno Depresivo Mayor

E.1.1.1

Medical condition in easily understood language

Depression

Depresión

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

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to demonstrate the efficacy of SPD489 when used as augmentation therapy in the treatment of major depressive disorder (MDD) in inadequate responders following an 8-week course of treatment with an antidepressant, as measured by the mean change in Montgomery-?sberg Depression Rating Scale (MADRS) total scores.

El objetivo primario es demostrar la eficacia de SPD489 al utilizarse
como terapia potenciadora para el tratamiento del trastorno depresivo
mayor (TDM) en los pacientes que muestran una respuesta inadecuada
tras 8 semanas de tratamiento con un antidepresivo (determinada
mediante el cambio medio de la puntuación total en la Escala de
valoración de la depresión de Montgomery y Asberg (MADRS).

E.2.2

Secondary objectives of the trial

Key Secondary
The key secondary objective is to demonstrate the effect of SPD489, when used as augmentation therapy in the treatment of MDD in inadequate responders following an 8-week course of treatment with an antidepressant, on quality of life (QoL) as measured by the Sheehan Disability Scale (SDS).

Additional secondary objectives are described in the protocol.

Secundario fundamental:
El objetivo secundario fundamental es demostrar el efecto de SPD489 al
utilizarse como terapia potenciadora para el tratamiento del trastorno
depresivo mayor (TDM) en los pacientes que muestran una respuesta
inadecuada tras 8 semanas de tratamiento con un antidepresivo, en
cuanto a la calidad de vida (CdV) determinada mediante la Escala de
discapacidad de Sheehan (EDS).

Los objetivos secundarios adicionales se describen en el protocolo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject has a primary diagnosis of non-psychotic major depressive disorder (single or recurrent) as defined by the Structured Clinical Interview for DSM-IV-TR disorders ? Axis-I (SCID-CT) that has lasted ?8 weeks prior to the Screening Visit (Visit 1).

Subject has a Montgomery Asburg Depression Rating Scale (MADRS) total score ?24 at the Lead-in Baseline Visit (Visit 2).

El paciente tiene un diagnóstico primario de trastorno depresivo mayor
no psicótico (único o recurrente), de acuerdo con la Entrevista Clínica
Estructurada del Manual Diagnóstico y Estadístico de los Trastornos
Mentales, Cuarta Edición - Revisión del Texto (SCID-CT), que se ha
prolongado ? 8 semanas con anterioridad a la visita de selección (Visita
1).
El paciente presenta una puntuación total en la MADRS? 24 en la visita
basal de inicio de antidepresivos (visita 2).

E.4

Principal exclusion criteria

Subject whose current episode of MDD has not responded to an adequate
treatment regimen (at least 6 weeks of treatment at the maximum
tolerated adult dose approved for the indication) with 2 or more
approved single antidepressant agents. Any subjects whose current
episode of MDD has not responded to an approved adjunctive treatment
strategy is to be excluded.

Subject who has a lifetime history of treatment-resistant depression,
defined as having not responded to adequate treatment (at least 8
weeks at the maximum tolerated adult dose approved for the indication)
with 2 or more treatment regimens, including, distinct classes of
approved single antidepressant agents and adjunctive treatment
stategies.

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 that is either
controlled with medications prohibited in this study or is uncontrolled
and associated with significant symptoms. Excluded are: any significant
Axis II disorders, any bipolar disorder, any current or lifetime psychosis,
post-traumatic stress disorder, anorexia nervosa, and blumia nervosa. A
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 the
Screening Visit (Visit 1) and/or Lead-in Baseline Visit (Visit 2), or 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.

- Paciente cuyo episodio actual de trastorno depresivo mayor no ha
respondido a un régimen de tratamiento adecuado (como mínimo 6
semanas de tratamiento a la dosis máxima tolerada en adultos aprobada
para la indicación) compuesto por dos o más fármacos antidepresivos
únicos aprobados. Se excluirá todo paciente cuyo episodio de TDM no haya respondido a una estrategia de tratamiento adyuvante aprobada.
-Pacientes con antecedentes de depresión resistente al tratamiento,
definida como la ausencia de respuesta a un tratamiento adecuado
(como mínimo 8 semanas de tratamiento a la dosis máxima tolerada en
adultos aprobada para la indicación) con dos o más regímenes de
tratamiento compuestos por fármacos antidepresivos únicos aprobados
de distintas clases.
- Paciente que en opinión del investigador se considera en riesgo de
suicidio, ya ha llevado a cabo un intento de suicidio en los últimos 3
años, o muestra actualmente pensamientos de suicido activos.
- Pacientes que presentan otro trastorno psiquiátrico concomitante que: o bien se controla con medicamentos prohibidos en este estudio, o bien no está controlado y se asocia a síntomas significativos. Las patologías excluidas son: cualquier trastorno significativo del Eje II (incluyendo el trastorno límite de la personalidad), cualquier trastorno bipolar, cualquier psicosis (actual o aparecida durante la vida del paciente), trastorno de stress postraumático, trastorno obsesivo-compulsivo, anorexia nerviosa y bulimia nerviosa. Pacientes que tienen antecedentes de problemas cardíacos graves que podrían hacerlos más vulnerables a los efectos simpaticomiméticos de un medicamento estimulante. Pacientes con antecedentes de hipertensión moderada a grave, un promedio (de 3 lecturas) de la tensión arterial sistólica en sedestación > 139 mmHg o un promedio (de 3 lecturas) de la tensión arterial diastólica > 89 mmHg en la visita de selección (visita 1) o en la visita basal de inicio (visita 2). Pacientes que presenten una enfermedad concurrente aguda o crónica o una condición médica inestable que pudiera empeorar y dar lugar a errores en los resultados de las evaluaciones de seguridad, aumentar el riesgo para el paciente, o dar lugar a dificultades para cumplir con el protocolo.

E.5 End points

E.5.1

Primary end point(s)

Change from Augmentation Baseline Visit (Visit 8 [Week 8]) to Visit 14 (Week 16/Any) in Montgomery-Asberg Depression Rating Scale (MADRS) total score.

Cambio en la puntuación total de EDS desde la visita basal del
tratamiento de potenciación (Visita 8 [Semana 8]) hasta la Visita 14
(Semana 16/otras) en la escala de clasificación de la depresión de
Montgomery-?sberg (MADRS).

E.5.1.1

Timepoint(s) of evaluation of this end point

? Randomized Subjects: Week -4 to -1, 0, 6, 8, 9, 10, 11, 12, 14, 16/Any
? Non-Randomized Subjects: Week -4 to -1, 0, 6, 8, 10, 12, 16/Any

? Pacientes aleatorizados: Semana -4 a -1, 0, 6, 8, 9, 10, 11, 12, 14,
16/otras
? Pacientes no aleatorizados: Semana -4 a -1, 0, 6, 8, 10, 12, 16/Otras

E.5.2

Secondary end point(s)

1) Change from the Augmentation Baseline Visit (Visit 8 [Week 8]) to Visit 14 (Week 16/Any) in Sheehan Disabillity Scale (SDS) total score.
2) Safety and tolerability as based on a) occurrence of treatment-emergent adverse events (TEAEs), b) response to Columbia Suicide Severity Rating Scale (C-SSRS), evaluations of blood pressure and pulse, c) clinical laboratory evalutions, and d) electrocardiograms (ECG)
3) Percent of Participants Achieving a 25% Response on the MADRS at Visit 14 (Week 16/Any)
4) Percent of Participants Achieving a 50% Response on the MADRS at Visit 14 (Week 16/Any)
5) Percent of Participants Achieving Remission on the MADRS at Visit 14 (Week 16/Any)
6) Change from Augmentation Baseline Visit (Visit 8 [Week 8]) over time in MADRS total score.
7) Change in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR)
8) Change from the Augmentation Baseline Visit (Visit 8 [Week 8]) to Visit 14 (Week 16/Any) in the Short Form-12 Health Survey V2 (SF-12V2)
9) Change from the Augmentation Baseline Visit (Visit 8 [Week 8]) to Visit 14 (Week 16/Any) in the EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D-5L index score)
10) Change from the Augmentation Baseline Visit (Visit 8 [Week 8]) to Visit 14 (Week 16/Any) in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (QLES-Q-SF)
11) Clinical Global Impressions - Severity of Illness (CGI-S) at Visit 2 (Week 0) and Visit 8 (Week 8)
12) Change in Clinical Global Impressions - Global Improvement (CGI-I) at Visit 14 (Week 16/Any)
13) Change in the Patient Resource Utilization Questionnaire (PRUQ)
14) Amphetamine Cessation Symptom Assessment (ACSA) at Visit 15 (Week 17/Any)

1)Cambio en la puntuación total Escala de discapacidad de Sheehan
(EDS) desde la visita basal del tratamiento de potenciación (Visita 8
[Semana 8]) hasta la Visita 14 (Semana 16/otras)
2) Evaluar la Seguridad y tolerabilidad basados en a) la aparición de
acontecimientos adversos emergentes relacionados con el tratamiento
(AASDT), b) la respuesta a la Escala Columbia para evaluar el riesgo de
suicidio, Columbia Suicide Severity Rating Scale (C-SSRS), c)
evaluaciones clínicas de laboratorio, y d) electrocardiogramas (ECG)
3) porcentaje de pacientes que alcanzan un 25% en la Respuesta al
MADRS en la Visita 14 (Semana16/Otras)
4) porcentaje de pacientes que alcanzan un 50% en la Respuesta al
MADRS en la Visita 14 (Semana16/Otras)
5) Porcentaje de pacientes que consigan la Remisión en la Respuesta al
MADRS en la Visita 14 (Semana16/Otras)
6) Cambio desde la visita basal del tratamiento de potenciación (Visita 8
[Semana 8]) a lo largo del tiempo en la puntuación total de MADRS.
7) Cambio en el Inventario rápido de la sintomatología depresiva -
autoinforme (QIDS-SR).
8) Cambio desde la la inicial del tratamiento de potenciación (Visita 8
[Semana 8]) a la Visita 14 (Seamana 16/Otras) en la encuesta de salud
SF-12 versión 2, forma breve (SF-12V2) .
9) Cambio desde la la inicial del tratamiento de potenciación (Visita 8
[Semana 8]) a la Visita 14 (Semana 16/Otras) en el cuestionario de
autoevaluación del grupo EuroQOL de 5 dimensiones y 5 niveles (EQ-5D-
5L).
10) Cambio desde la la inicial del tratamiento de potenciación (Visita 8
[Semana 8]) a la Visita 14 (Semana 16/Otras) el Cuestionario de calidad
de vida, satisfacción y placer, forma breve (Q LES-Q-SF).
11) Impresión Clínica Global - Mejoría Global (ICG-MG) en la Visita 2
(Semana 0) y Visita 8 (Semana 8).
12) Cambio en la Impresión Clínica Global - Mejoría Global (ICG-MG) en
la Visita 14 (Semana 16/Otras)
13) Cambio en el cuestionario de utilización de recursos del paciente
(Patient Resource Utilization Questionnaire (PRUQ))
14) Evaluación de los síntomas de abandono de las anfetaminas (ACSA)
en la Visita 15 (Semana 17/Otras)

E.5.2.1

Timepoint(s) of evaluation of this end point

1 ) SDS
? Randomized (R): Week (Wk) 0, 8, 9, 10, 11, 12, 14, 16/Any
? Non-randomized (NR): 0, 8, 10, 12, 16/Any

2a)
? R: Wk 8, 9, 10, 11, 12, 14, 16/Any, 17/Any
? NR: 8, 10, 12, 16/Any, 17/Any
2b)
? R: Wk -1 to -4, 0, 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 14, 16/Any, 17/Any
? NR: -1 to -4, 0, 1, 2, 3, 4, 6, 8, 10, 12, 16/Any, 17/Any
2c)
? R & NR: Wk -4 to -1, 0, 8, 12, 16/Any
2d)
? R & NR: Wk -4 to -1, 0, 8, 16/Any
3-6)
? R: Wk -4 to -1, 0, 6, 8, 9, 10, 11, 12, 14, 16/Any
? NR: -4 to -1, 0, 6, 8, 10, 12, 16/Any
7-10) R & NR: Wk 0, 8, 16/Any
11) R & NR: Week 0 and 8
12)
? R: Wk 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 14, 16/Any
? NR: 1, 2, 3, 4, 6, 8, 10, 12, and 16/Any
13) R & NR: Wk 0, 8, 12, 16/Any
14) R & NR: Wk 17/Any

1 ) EDS-Escala de discapacidad de Sheehan
? Aleatorizados (A): Semana (Sem) 0, 8, 9, 10, 11, 12, 14, 16/Otra
? No aleatorizados (NA): 0, 8, 10, 12, 16/Otras
2a)
? A: Sem 8, 9, 10, 11, 12, 14, 16/Otras, 17/Otras
? NA: 8, 10, 12, 16/Otra, 17/Otras
2b) ? A: Sem -1 a -4, 0, 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 14, 16/Otras,
17/Otras
? NA: -1 a -4, 0, 1, 2, 3, 4, 6, 8, 10, 12, 16/Otras, 17/Otras
2c)
? A y NA: Sem -4 a -1, 0, 8, 12, 16/Otras
2d)
? A y NA: Sem -4 a -1, 0, 8, 16/Otras
3-6) ? A: Sem -4 a -1, 0, 6, 8, 9, 10, 11, 12, 14, 16/Otras
? NA: -4 a -1, 0, 6, 8, 10, 12, 16/Otras
7-10) A y NA: Sem 0, 8, 16/Otras
11) A y NA: Sem 0 y 8
12) ? A: Sem 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 14, 16/Otras
? NA: 1, 2, 3, 4, 6, 8, 10, 12, y 16/Otras
13) A y NA: Sem 0, 8, 12, 16/Otras
14) A y NA: Sem 17/Otras

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Withdrawal symptoms

Síntomas de abstinencia

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Flexible Dose Titration

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Canada

Croatia

France

Mexico

Spain

United States

E.8.7

Trial has a data monitoring committee

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

Last Subject Last Visit

Último Paciente Última Visita

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

1012

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

1034

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Eligible subjects will have the option to enter a 12-month extension safety and tolerability study.

Los pacientes elegibles tendrán la opción de continuar en un estudio
de extensión de 12 meses de duración para evaluar la seguridad y la
tolerabilidad.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-12-23

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials