Clinical Trials Register

Summary
EudraCT Number:	2021-001333-38
Sponsor's Protocol Code Number:	CAVES
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-07-19
Trial 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

2021-001333-38

A.3

Full title of the trial

Cognitive effects of adjuntive Vortioxetine in early Schizophrenia

Efectos cognitivos de vortioxetina adyuvante en la esquizofrenia temprana

A.3.1

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

Clinical trial to study the effect of an already authorized drug on other pathologies by administering it to people with a recent diagnosis of schizophrenia.

Ensayo clínico para estudiar el efecto que tiene un fármaco ya autorizado en otras patologías administrándolo en personas con reciente diagnóstico de esquizofrenia.

A.3.2

Name or abbreviated title of the trial where available

Cognitive effects of adjuntive Vortioxetine in early Schizophrenia

Efectos cognitivos de vortioxetina adyuvante en la esquizofrenia temprana

A.4.1

Sponsor's protocol code number

CAVES

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	Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Consejería de salud
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Unidad de Investigación Clínica y Ensayos Clínicos
B.5.2	Functional name of contact point	UICEC-HUVR
B.5.3	Address:
B.5.3.1	Street Address	Av. Manuel Siurot SN
B.5.3.2	Town/ city	Sevilla
B.5.3.3	Post code	41013
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034955013414
B.5.5	Fax number	0034954232992
B.5.6	E-mail	eecc.huvr@gmail.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	BRINTELLIX
D.2.1.1.2	Name of the Marketing Authorisation holder	H. Lundbeck A/S
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	VORTIOXETINA
D.3.2	Product code	N06AX26
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	HALOPERIDOL
D.3.2	Product code	N05AD01
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Pimozida
D.3.2	Product code	NO5AG02
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Olanzapina
D.3.2	Product code	NO5A H03
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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: 5
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Risperidona
D.3.2	Product code	NO5AX08
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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: 6
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Chlorpromazine
D.3.2	Product code	N05AA01
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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: 7
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Thioridazine
D.3.2	Product code	N05AC02
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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: 8
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Quetiapine
D.3.2	Product code	N05AH04
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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: 9
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Ziprasidone
D.3.2	Product code	N05AE04
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.3.11 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: 10
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Spain
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	aripiprazole
D.3.2	Product code	N05AX12
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Early schizophrenia

Esquizofrenia temprana

E.1.1.1

Medical condition in easily understood language

Newly evolving schizophrenia

Esquizofrenia de reciente evolución

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

Primary objective: To assess the effectiveness of Vortioxetine vs. TAU in the treatment of cognitive impairments in early psychosis, measured by the change From Baseline to Week 24 in Brief Assessment of Cognition in Schizophrenia (BACS App) scores using the Composite Z-score Defined as the Weighted Sum of the Individual Patient Z-scores. [Time Frame: Baseline, week 24, week 26 and week 50]

Objetivo principal: evaluar la eficacia de la vortioxetina frente al TAU en el tratamiento del deterioro cognitivo en la esquizofrenia de reciente diagnóstico, medida por el cambio desde el inicio hasta la semana 24 (y desde la semana 26 a la semana 50 en el 2º período) en las puntuaciones de la Escala BACS App, utilizando la Puntuación Compuesta Z definida como la suma ponderada de la Puntuación Individual Z del paciente (Tiempo de medida: visita basal, semana 24, semana 26 y semana 50).

E.2.2

Secondary objectives of the trial

Secondary objective: To assess the effectiveness of Vortioxetine vs. TAU in the treatment of negative symptoms in early psychosis, measured by the change in Negative Symptoms severity (SANS, NSA-4 total scores) from baseline to end of trial. [Time Frame: Baseline, week 4, week 12, week 24, week 26, week 30, week 38 and week 50]
Other objectives:
- To assess the effectiveness of Vortioxetine vs. TAU in the treatment of cognitive impairments in early psychosis, measured by the change in general functioning (Global Assessment of Functioning (GAF) total score) [Time Frame: baseline, week 12, week 24, week 26, week 38 and week 50]
- To assess the safety of Vortioxetine in patients with early psychosis measured through the communication of any serious adverse event evaluated for relationship with the Investigational Medicinal Product (IMP) [Time Frame: from informed consent form (ICF) signature to 52 weeks]

Objetivo secundario: evaluar la eficacia de la vortioxetina frente al TAU en el tratamiento de los síntomas negativos en la esquizofrenia de reciente diagnóstico, medida por el cambio en la gravedad de los síntomas negativos (puntuaciones totales de SANS, NSA-4) desde el inicio al fin(Tiempo de medida: visita basal, semana 4, semana 12, semana 24, semana 26, semana 30, semana 38 y semana 50).

Otros objetivos:
- Evaluar la eficacia de la vortioxetina frente al TAU en el tratamiento de las deficiencias cognitivas en la esquizofrenia de reciente diagnóstico, medida por el cambio en el funcionamiento general (puntuación total GAF) (Tiempo de medida: visita basal, semana 12, 24, 26, 38 y 50)
- Evaluar la seguridad de la vortioxetina en pacientes con esquizofrenia de reciente diagnóstico medida a través de la comunicación de cualquier evento adverso grave evaluado en relación con el Tratamiento Experimental (Tiempo de medida: desde la firma de consentimiento hasta la semana 52).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Outpatient
2. Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM - SCID) diagnosis of Schizophrenia spectrum disorders.
3. Age >18-50 years old
4. Stable antipsychotic medication doses during at least 4 weeks ( all second generation antipsychotics excluding clozapine).
5. No antidepressant treatment for at least 8 weeks prior to randomization.
6. PANSS Negative subscore >14 with at least two of the items at a level >/=4 (moderate)
7. PANSS Positive subscore </=14 with not more than one of the items at a level >/=4 (moderate)
8. Hamilton Depression Rating Scale (HAMD-17) total score </=12
9. Simpson Angus Score of any item <2
10. Behaviorally Anchored Rating Scale (BARS) of any item </= 1
11. Competent and willing to sign informed consent
12. The patient, if a woman, must: agree not to try to become pregnant during the study and use adequate, highly effective contraception

1. Paciente ambulatorio.
2. Reciente diagnóstico SCID de los trastornos del espectro de la esquizofrenia (el diagnóstico de la enfermedad debe haber sido como máximo 3 años antes de la firma del consentimiento).
3. Edad comprendida entre 18 y 50 años.
4. Dosis estables de medicación antipsicótica durante al menos 4 semanas (todos los antipsicóticos de segunda generación, excluyendo clozapina).
5. Ningún tratamiento antidepresivo durante al menos 8 semanas antes de la aleatorización.
6. PANSS: puntuación negativa > 14 con al menos dos de los elementos en un nivel ≥ 4 (moderado)
7. PANSS: puntuación positiva ≤ 14 con no más de uno de los elementos en un nivel ≥ 4 (moderado).
8. Puntaje total de HAMD-17 ≤ 12
9. Puntuación de Simpson Angus de cualquier ítem <2.
10. BARS de cualquier ítem ≤ 1
11. Competente y dispuesto a firmar el consentimiento informado
12. En caso de que el paciente sea mujer potencialmente fértil, debe aceptar no quedarse embarazada durante el estudio, así como el uso de anticonceptivos adecuados y altamente efectivos.

E.4

Principal exclusion criteria

1. Patients taking any antidepressant and its use cannot be discontinued at least 8 weeks prior to randomization.
2. Structural brain disease (based on previous medical records)
3. Cognitive disability by history and estimated intelligence quotient (IQ) <70 (ID DSM-5 diagnosis).
4. Any serious chronic medical illnesses that may interfere with the patient's ability to comply with the study procedures or that will interfere with cognition.
5. Organic mental disorders, or mental disorders due to a general medical condition. Any neurological or neurodegenerative disorders.
6. Any current diagnosis of substance abuse or dependence.
7. Serious risk of suicide.
8. Patients with thyroid conditions.
9. Intolerance to or inefficacy of vortioxetine in the past. Patients who had failed treatment with vortioxetine were also excluded.
10. Pregnant or breastfeeding female.

1. Pacientes que tomen cualquier antidepresivo y su uso no pueda ser interrumpido al menos 8 semanas antes de la aleatorización.
2. Enfermedad cerebral estructural (basada en registros médicos anteriores).
3. Discapacidad cognitiva por antecedentes y coeficiente intelectual estimado < 70 (diagnóstico ID DSM-5).
4. Cualquier enfermedad médica crónica grave que pueda interferir con la capacidad del paciente para cumplir con los procedimientos del estudio o que interfiera con la cognición.
5. Trastornos mentales orgánicos o trastornos mentales debidos a una condición médica general. Cualquier trastorno neurológico o neurodegenerativo.
6. Cualquier diagnóstico actual de abuso o dependencia de sustancias.
7. Riesgo grave de suicidio.
8. Pacientes con enfermedades de la glándula tiroides.
9. Intolerancia o ineficacia de la vortioxetina en el pasado. Pacientes que han tenido tratamiento fallido con vortioxetina también serán excluidos.
10. Mujer embarazada o en período de lactancia.

E.5 End points

E.5.1

Primary end point(s)

Primary outcome measures: Cognitive functioning improvement assessed by the change in BACS App scores.

Medidas de resultado primarias: Mejora del funcionamiento cognitivo evaluada por el cambio en las puntuación/score de la aplicación BACS.

E.5.1.1

Timepoint(s) of evaluation of this end point

Cognitive functioning will be assessed at Baseline, week 24, week 26 and week 50

El funcionamiento cognitivo se evaluará en visita basal, semana 24, semana 26 y semana 50

E.5.2

Secondary end point(s)

Secondary outcome:
- Negative symptoms severity improvement measured by the change in Negative Symptoms severity (SANS, NSA-4 total scores)
from baseline to endpoint [Time Frame: Baseline, week 4, week 12, week 24, week 26, week 30, week 38 and week 50]

Other outcomes:
- Functional improvement measured by the change in general functioning (GAF total score) [Time Frame: baseline, week 12, week 24, week 26, week 38 and week 50]
- Assessment of the frequency, severity and relationship with study medication, even reasons for withdrawal if applies.

Resultado secundario:
- mejoría de la gravedad de los síntomas negativos medida por el cambio en la gravedad de los síntomas negativos (SANS, puntuaciones totales de NSA-4) desde el inicio (baseline) hasta el punto final [Marco temporal: visita basal, semana 4, semana 12, semana 24, semana 26, semana 30, semana 38 y semana 50].

Otros resultados:
- mejora funcional medida por el cambio en el funcionamiento general (puntuación total GAF) [Marco de tiempo: visita basal, semana 12, 24, 26, 38 y 50].
- evaluación de la frecuencia, gravedad y relación con la medicación del estudio. incluso razones para la retirada si aplica.

E.5.2.1

Timepoint(s) of evaluation of this end point

- Negative Symptoms severity (SANS, NSA-4 total scores) from baseline to endpoint [Baseline, week 4, week 12, week 24, week 26, week 30, week 38 and week 50]
- Functional improvement measured by the change in general functioning (GAF total score) [Time Frame: baseline, week 12, week 24, week 26, week 38 and week 50]
- To assess the safety of Vortioxetine in patients with early schizophrenia measured through the communication of any serious adverse event evaluated for relationship with the IMP. [Time Frame: from ICF signature to 52 weeks]

- Puntuaciones totales de SANS, NSA-4 desde el inicio hasta la finalización (franja de tiempo: visita basal, semana 4, semana 12, semana 24, semana 26, semana 30, semana 38 y semana 50)
- mejora funcional medida por el cambio en el funcionamiento general (puntuación total GAF) [Marco de tiempo: visita basal, semana 12, 24, 26, 38 y 50].
- Evaluar la seguridad de la vortioxetina en pacientes con esquizofrenia temprana medida a través de la comunicación de cualquier evento adverso grave evaluado en relación con el Tratamiento Experimental. (franja de tiempo: desde la firma de consentimiento hasta la semana 52).

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

Yes

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

E.6.13

Others

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)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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 total timing of the trial will last 52 weeks. Last visit of the last subject.

El tiempo total de duración del ensayo será 52 semanas. Última visita del último sujeto.

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

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:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Prior to signing the consent, the researcher will evaluate the patient to consider their ability to sign the consent. If you are not qualified, it will be signed by your informant.

Previamente a la firma del consentimiento, el investigador hará una evaluación al paciente para considerar su capacidad para firmar el consentimiento. Si no está capacitado, lo firmará su informante.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

"None"

"Ninguno"

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	UICEC-HUVR
G.4.3.4	Network Country	Spain

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-10-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-16

P. End of Trial
P.	End of Trial Status	Ongoing

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