Clinical Trials Register

Summary
EudraCT Number:	2008-001441-26
Sponsor's Protocol Code Number:	12450A
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-03-17
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2008-001441-26

A.3

Full title of the trial

A randomised, double-blind, parallel-group, fixed-dose study exploring the efficacy and safety of Lu AE58054 as augmentation therapy to risperidone in patient with schizophrenia

A.4.1

Sponsor's protocol code number

12450A

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	H. Lundbeck A/S
B.1.3.4	Country	Denmark
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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.2.1.1.2	Name of the Marketing Authorisation holder	RATIOPHARM ITALIA Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Coated tablet
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	Risperidone
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.3	Concentration number	1
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	No
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	Lu AE58054
D.3.2	Product code	Lu AE58054
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	ANTIPSYCHOTICS
D.3.9.2	Current sponsor code	LU AE58054
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	60
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

schizophrenia

Schizzofrenia

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10039626
E.1.2	Term	Schizophrenia
E.1.2	System Organ Class	10037175 - Psychiatric disorders

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 explore the efficacy of a fixed dose of Lu AE58054 (120 mg/day) as augmentation therapy to risperidone (4 to 8 mg/day), compared to risperidone with placebo, after 12 weeks of treatment, by measuring the change in the PANSS total score in patients with schizophrenia.

Indagare l'efficacia di una dose fissa di Lu AE58054 (120 mg/giorno) in veste di terapia aggiuntiva al risperidone (da 4 a 8 mg/giorno), in paragone al risperidone con placebo, dopo 12 settimane di trattamento, misurando la variazione nel punteggio PANSS totale in pazienti affetti da schizofrenia

E.2.2

Secondary objectives of the trial

To explore the effect of a fixed dose of Lu AE58054 (120 mg/day) as augmentation therapy to risperidone (4 to 8 mg/day), compared to risperidone with placebo, after 12 weeks of treatment on 1)neurocognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) battery 2)depressive symptoms using the Calgary Depression Scale for Schizophrenia (CDSS)3)quality of life using the Schizophrenia Quality of Life (S-QoL) scale 4)treatment response using the Clinical Global Impression Severity of Illness (CGI-S) and the Clinical Global Impression Global Improvement (CGI-I) scales 5)body weight, body mass index (BMI), waist circumference and laboratory parameters including fasting serum levels of blood lipids, blood glucose and HbA1c. To determine the population pharmacokinetics of Lu AE58054 in patients with schizophrenia and relate it to relevant pharmacodynamic parameters. To explore the associations between biomarkers (that is, genetic variants)and clinical features

An eff di una dose fissa di Lu AE58054(120 mg/giorno)in veste di terap agg al risperidone(da 4 a 8 mg/giorno),in paragone al risperidone con pl,dopo 12 sett di tratt,su:il rendimento neurocognitivo utilizzando la batteria Brief Assessment of Cognition in Schizophrenia(BACS)i sintomi depressivi impiegando la Depression Scale for Schizophrenia(CDSS)la QdV utilizzando la scala Schizophrenia QoLla risp al tratt facendo uso delle scale Clinical Global Impression Severity of Illnesse Clinical Global Impression Global Improvement il peso corporeo, BMI,la circonferenza della vita e i parametri dilab,inclusi i livelli sierici,a digiuno,dei lipidi nel sangue,del glucosio ematico e dell HbA1c Ricavare la PK di pop relativa a Lu AE58054 in paz affetti da schizofrenia e correlarla con i param PC di rilevanza.An le associaz tra biomarcatori e peculiarità cliniche quali ad esempio i sintomi di malattia,la risp farmacolog o gli EA

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

PHARMACOGENETIC:
Vers:1
Date:2008/07/04
Title:
Objectives:

LIFE QUALITY:
Vers:1
Date:2008/07/04
Title:
Objectives:

FARMACOGENETICA:
Vers:1
Data:2008/07/04
Titolo:A randomised, double-blind, parallel-group, fixed dose study exploring the efficacy and safety of Lu AE58054 as augmentation therapy to risperidone in patients with schizophrenia.
Obiettivi:Currently the pharmacogenetics of Lu AE58054 is not known. The purpose of the sample you are giving is to find out if a gene (or combinations of genes) can be used to predict the response to Lu AE58054. Similarly, a study may be conducted which tries to find genes that have a relationship to schizophrenia.

QUALITA DELLA VITA:
Vers:1
Data:2008/07/04
Titolo:A randomised, double-blind, parallel-group, fixed dose study exploring the efficacy and safety of Lu AE58054 as augmentation therapy to risperidone in patients with schizophrenia.
Obiettivi:

E.3

Principal inclusion criteria

The patients to be included in this study are men or women, with a primary diagnosis of schizophrenia, for whom a change in antipsychotic treatment is indicated since they are only partially responding to their current risperidone treatment. The partial response should not be due to poor compliance to this treatment. The patients must have clinically significant symptoms at screening and baseline and be on an optimised dose of risperidone for the last 4 weeks prior to screening and during the 2-week run-in period prior to baseline, with an absence of acute exacerbations. The patient signed informed consent prior to the conduct of any study specific procedures. The patient has a primary diagnosis of schizophrenia according to the Diagnostics and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR). The patient is a man or woman aged between 18 and 65 years (extremes included). The patient has been on an optimised dose of risperidone (within 4-8 mg/day) for the treatment of schizophrenia for a minimum of 4 weeks prior to screening and during the 2-week lead-in period prior to baseline. The patient has a PANSS total score between 70 and 100 (extremes included) at screening and has had an improvement of <20% in the PANSS total score at baseline. The patient has a score of 4 (moderate) on the following three PANSS items at screening and baseline:  P2 (conceptual disorganisation)  P7 (hostility)  G8 (uncooperativeness) The patient has a CGI-S score of ≥4 (moderately ill) at screening and baseline.

I pazienti che potranno essere inclusi in questa ricerca sono di sesso maschile o femminile, con una diagnosi primaria di schizofrenia, e per i quali e` indicata una variazione del trattamento anti-psicotico dato che esibiscono una risposta solo parziale alla terapia corrente con risperidone alla quale sono sottoposti. La risposta parziale non deve essere dovuta a scarsa compliance con questo trattamento. I pazienti devono presentare sintomi clinicamente significativi allo screening e al basale, e assumere una dose ottimizzata di risperidone per le ultime 4 settimane prima dello screening e nel corso del periodo di run-in, della durata di 2 settimane, precedente il basale, in assenza di esacerbazioni acute. Prima di condurre una qualunque delle specifiche procedure connesse con lo studio, il paziente ha firmato un consenso informato. Il paziente presenta, in base al Diagnostics and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR), una diagnosi primaria di schizofrenia. Il paziente e` di sesso maschile o femminile e di eta` compresa fra i 18 e i 65 anni (estremi inclusi). Il paziente ha assunto una dose ottimizzata di risperidone (nell`intervallo compreso fra 4 e 8 mg/giorno) per il trattamento della schizofrenia per un minimo di 4 settimane prima dello screening e durante il periodo di lead-in, della durata di 2 settimane, prima del basale. Il paziente ha un punteggio PANSS totale compreso tra 70 e 100 (estremi inclusi) allo screening, e ha mostrato un miglioramento <20% nel punteggio PANSS totale al basale. Allo screening e al basale, il paziente esibisce un punteggio 4 (moderato) rispetto alle seguenti tre voci della PANSS:  P2 (disorganizzazione concettuale)  P7 (ostilita`)  G8 (mancanza di cooperazione) Allo screening e al basale, il paziente mostra un punteggio CGI-S ≥4 (malattia moderata).

E.4

Principal exclusion criteria

The patient has a current Axis I primary psychiatric diagnosis other than schizophrenia according to the DSM-IV-TR criteria. The patient is in an emergency situation for urgent relief of symptoms. The patient has had an acute exacerbation requiring hospitalisation within the last 6 weeks. The patient has a diagnosis of mental retardation or history of pervasive developmental disorder. The patient has clinically significant extrapyramidal symptoms (SAS score >6). The patient has abused drugs or alcohol within the last 6 months preceding the study. The patient is resistant to antipsychotic treatment, according to the investigator s judgement. The patient has been treated with an antipsychotic, other than risperidone, within 4 weeks prior to screening.

Al momento il paziente presenta, in base ai criteri DSM-IV-TR, una diagnosi psichiatrica primaria di Asse I diversa dalla schizofrenia. Il paziente si trova in situazione di emergenza dovuta a urgente alleviazione dei sintomi. Il paziente ha subito, entro le ultime 6 settimane, un`esacerbazione acuta che ha richiesto il ricovero in ospedale. Il paziente presenta una diagnosi di ritardo mentale o di storia di disordine pervasivo dello sviluppo. Il paziente esibisce sintomi extrapiramidali clinicamente significativi (punteggio SAS >6).

E.5 End points

E.5.1

Primary end point(s)

Change in PANSS total score from baseline to Week 12, using last observation carried forward (LOCF).

Variazione nel punteggio PANSS totale dal basale alla settimana 12, usando l'ultima osservazione portata a termine (LOCF, last observation carried forward).

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

Yes

E.6.11

Pharmacogenomic

Yes

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)

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	9
F.4.2	For a multinational trial
F.4.2.1	In the EEA	95
F.4.2.2	In the whole clinical trial	120

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

2009-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-11-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-01-15

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