Clinical Trials Register

Summary
EudraCT Number:	2011-004211-23
Sponsor's Protocol Code Number:	PI11-PR-KRYSTKOWIAK
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-10-04
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

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2011-004211-23

A.3

Full title of the trial

Etude d’efficacité et d’acceptabilité de la Tétrabénazine dans le syndrome tardif aux neuroleptiques : Etude randomisée multicentrique en groupes parallèles en double aveugle versus placebo «XELADYS»

A.3.1

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

Etude d’efficacité et d’acceptabilité de la Tétrabénazine dans le syndrome tardif aux neuroleptiques

A.3.2

Name or abbreviated title of the trial where available

XELADYS

A.4.1

Sponsor's protocol code number

PI11-PR-KRYSTKOWIAK

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	CHU Amiens
B.1.3.4	Country	France
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	EUSA Pharma
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHU Amiens
B.5.2	Functional name of contact point	Loïc Fin
B.5.3	Address:
B.5.3.1	Street Address	Direction de la Recherche Clinique - CHU Nord
B.5.3.2	Town/ city	Amiens
B.5.3.3	Post code	80054
B.5.3.4	Country	France
B.5.4	Telephone number	33322668000
B.5.5	Fax number	33322667911
B.5.6	E-mail	fin.loic@chu-amiens.fr

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	XENAZINE
D.2.1.1.2	Name of the Marketing Authorisation holder	EUSA Pharma
D.2.1.2	Country which granted the Marketing Authorisation	France
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	XENAZINE
D.3.4	Pharmaceutical form	Buccal 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.3.9.1	CAS number	58-46-8
D.3.9.3	Other descriptive name	TETRABENAZINE
D.3.9.4	EV Substance Code	SUB10939MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	75 to 200
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	Buccal tablet
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

syndrome tardif aux neuroleptiques

E.1.1.1

Medical condition in easily understood language

syndrome tardif aux neuroleptiques

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10043118
E.1.2	Term	Tardive dyskinesia
E.1.2	System Organ Class	10029205 - Nervous system 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

Efficacité de la tétrabénazine (Xénazine®) (30% d’amélioration) sur le syndrome tardif aux neuroleptiques évalué par l’échelle Extrapyramidal Symptoms Rating Scale (ESRS)

E.2.2

Secondary objectives of the trial

- Amélioration de l’Abnormal Involuntary Movement Scale, AIMS (meilleur score, 0 ; pire score, 40).
- Amélioration d’un sous-score de l’ESRS, l’ESRS 2, défini comme étant le score ESRS total moins le score de la partie II.
- Amélioration du score d’Impression Clinique Globale, CGI-amélioration (non évaluée, 0 ; fortement aggravée, 7).
- Amélioration de la qualité de vie sur la SF36.
- Bonne tolérance neurologique, psychiatrique et générale.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patient présentant un syndrome tardif aux neuroleptiques invalidant (entraînant un handicap fonctionnel et/ou un retentissement dans la vie quotidienne selon l’appréciation de l’investigateur et/ou du patient et/ou de l’entourage du patient)
- Patient avec syndrome tardif persistant malgré l’arrêt du neuroleptique depuis plus de 6 mois ou patients avec syndrome tardif sous traitement neuroleptique à dose stable depuis au moins 6 mois et qui ne nécessitera pas a priori d’augmentation de dose pendant la durée de l’étude
- MADRS < 18
- QTc < 450 ms pour les hommes et < 470 pour les femmes

E.4

Principal exclusion criteria

- Patient sans sécurité sociale
- Durée du traitement neuroleptique incriminé < 3 mois
- Démence selon le DSM IV et MMS < 24
- Akathisie
- Pathologie psychiatrique non stabilisée depuis 6 mois et/ou qui pourrait nécessiter une adaptation d’un traitement neuroleptique pendant la durée de l’étude
- Grossesse et allaitement
- Femme en activité génitale sans contraception efficace (stérilet ou pilule œstro-progestative)
- Hypersensibilité à la tétrabénazine
- Insuffisance rénale
- Médicaments: IMAO non sélectifs, dopaminergiques (antiparkinsoniens ou autres) arrêtés depuis moins de 4 semaines
- Présence d’une autre pathologie grave
- Incapacité à donner son consentement
- Incapacité à respecter les consignes du protocole, à l’appréciation de l’investigateur
- Sujet participant à une autre recherche simultanément
- Galactosémie congénitale, syndrome de malabsorption du glucose ou déficit en lactase

E.5 End points

E.5.1

Primary end point(s)

L’effet du traitement sera évaluée par l’échelle ESRS (Extrapyramidal Symptoms Rating Scale) (meilleur score, 0; pire score, 236).

E.5.1.1

Timepoint(s) of evaluation of this end point

Quatre évaluations :
V1 (semaine 2) : visite d'inclusion (baseline)
V4 (semaine 7) : fin de phase de titration
V6 (semaine 12): fin de phase de maintien
V7 (semaine 14): fin de wash-out - visite de fin d'étude

E.5.2

Secondary end point(s)

a) Abnormal Involuntary Movement Scale (meilleur score, 0; pire score, 40)
b) Sous-score ERSR 2 (score total – partie II: meilleur score, 0; pire score, 158) ; le choix de ce sous-score se justifie en raison de la possibilité que l’amélioration de l’ESRS total puisse être masquée par l’induction d’un syndrome parkinsonien représenté par la partie II de l’ESRS que nous avons donc choisi de soustraire afin d’aboutir à l’ESRS 2.
c) Amélioration du score d’Impression Clinique Globale, CGI-amélioration (échelle ordinale en 8 catégories: non évaluée, 0 ; fortement aggravée, 7)
d) Echelle générique de qualité de vie SF36
e) Tolérance: consultation de psychiatrie, UPDRS III (syndrome parkinsonien), échelle d’Epworth (somnolence diurne excessive), MADRS (syndrome dépressif), ECG (intervalle QT), TA, pouls, hypotension artérielle orthostatique, poids

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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)

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

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

E.8.4.1

Number of sites anticipated in 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

Dernière visite du dernier patient

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)

Yes

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.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)

Le suivi obligatoire dans le cadre de cette étude s’arrête à la 12ème semaine (V7).
Le suivi du patient au delà de cette période sera laissé à l'appréciation de l'investigateur en charge du patient

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

2011-11-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-18

P. End of Trial
P.	End of Trial Status	Completed

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