Clinical Trials Register

Summary
EudraCT Number:	2009-015833-66
Sponsor's Protocol Code Number:	50/0811
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:	2012-04-18
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2009-015833-66

A.3

Full title of the trial

Ropinirole 24h prolonged release and motor fluctuations: a study to control the wearing-off induced by dopamine agonists immediate release

Ropinirolo a rilascio prolungato e fluttuazioni motorie: studio per valutare il fenomeno del wearing off indotto dai dopamino agonisti a breve emivita

A.3.1

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

Ropinirole 24h prolonged release and motor fluctuations: a study to control the wearing-off induced by dopamine agonists immediate release

Ropinirolo a rilascio prolungato e fluttuazioni motorie: studio per valutare il fenomeno del wearing off indotto dai dopamino agonisti a breve emivita in pazienti affetti da malattia di Parkinson in fase intermedia

A.4.1

Sponsor's protocol code number

50/0811

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	CASA DI CURA PRIVATA S.RAFFAELE - PISANA
B.1.3.4	Country	Italy
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	GlaxoSmithKline SpA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS San Raffaele Pisana
B.5.2	Functional name of contact point	CTC Fabrizio Stocchi
B.5.3	Address:
B.5.3.1	Street Address	Via della Pisana 235
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00163
B.5.3.4	Country	Italy
B.5.4	Telephone number	0666058456
B.5.5	Fax number	0666058486
B.5.6	E-mail	fabrizio.stocchi@sanraffaele.it

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	REQUIP*28CPR 8MG R.P.
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	Prolonged-release 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	ROPINIROLE
D.3.9.1	CAS number	91374-21-9
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB10380MIG
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	8
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.2.1.1.1	Trade name	REQUIP*21CPR 5MG
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXOSMITHKLINE SpA
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	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	ROPINIROLE
D.3.9.1	CAS number	91374-21-9
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB10380MIG
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	5
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.2.1.1.1	Trade name	MIRAPEXIN*30CPR 0,7MG
D.2.1.1.2	Name of the Marketing Authorisation holder	BOEHRINGER INGELHEIM IT.SpA
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	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	PRAMIPEXOLE
D.3.9.1	CAS number	104632-26-0
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB09990MIG
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	.7
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

Parkinson's Disease

Malattia di Parkinson

E.1.1.1

Medical condition in easily understood language

Parkinson's Disease

Malattia di Parkinson

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	LLT
E.1.2	Classification code	10013113
E.1.2	Term	Disease Parkinson's
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

The PK profile of Ropinirole PR allows a continuous dopaminergic stimulation at receptors D2/D3 that could be translated - in a clinical setting- in an improved efficacy in reducing the wearing off time versus the DA agonists immediate release. The rational of this study is to evaluate the effect of ropinirole 24h prolonged release (Ropinirole PR) on wearing OFF induced by dopamine agonist’s immediate release (Ropinirole IR, Pramipexole IR)

Il ropinirolo a rilascio prolungato (RRP), registrato in Italia nel Giugno del 2008, grazie al nuovo sistema di rilascio controllato geomatrix consente di avere livelli di farmaco stabili sull’arco delle 24 ore assicurando una stimolazione più continua e fisiologica. In questo studio pilota, randomizzato in aperto con valutazione in cieco, si vuole verificare se l’introduzione del RRP al posto dei dopamino agonisti a breve emivita, consenta di migliorare il fenomeno del WEARING-OFF in pazienti parkinsoniani in monoterapia.

E.2.2

Secondary objectives of the trial

Mean change from baseline in the PDQ39 Mean change from baseline in Parkinson’s Disease Sleep Scale. Proportion of subjects with a score of much improved or very much improved on the CGI-I scale Mean change from baseline in the UPDRS - Motor Score Mean change from baseline in the UPDRS - Activities of Daily Living Adverse events incidence rate

Valutazione e modifica delle scale: UPDRS II e III, Scale del sonno PDSS, CGI del miglioramento, effetti collaterali

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply: Diagnosis of idiopathic Parkinson’s disease (according to modified Hoehn & Yahr criteria Stages I-IV) Subjects ia a stable DA agonists dose regimen for at least 18 months Subjects provided written informed consent for the study. Subjects are willing and able to comply with study procedures, including diary card completion and follow-up clinic visits.

Saranno studiati venti pazienti con Malattia di Parkinson idiopatica, in trattamento monoterapico con ropinirolo standard o pramipexolo, che presentano fluttuazioni motorie. Verranno studiati solo pazienti in grado di riempire un diario clinico ON/OFF e firmare il consenso informato. I pazienti saranno randomizzati per seguire o la terapia precedente o per cambiare su RRP.

E.4

Principal exclusion criteria

1. Late stage advanced subjects demonstrating incapacitating dyskinesias 2. Presence, or history within the previous 3 months, of significant and/or uncontrolled psychiatric, haematological, renal, hepatic, endocrinological, neurological (other than Parkinson’s disease), or cardiovascular disease or active malignancy (other than basal cell cancer). 3. Any abnormality, at screening, that the investigator deems to be clinically relevant on history, physical examination and in diagnostic laboratory tests including ECG. 4. Recent history of severe dizziness or fainting due to postural hypotension on standing. 5. Clinical dementia that in the judgment of the investigator would preclude assessment of the subject. 6. Subjects with neurotic behaviour, crippling degenerative arthritis or limb amputations, which would preclude efficacy or safety assessments. 7. Subjects with prior or current major psychosis (e.g. schizophrenia or psychotic depression) e.g., scoring 3 or 4 on UPDRS item 2 (thought disorder) or item 3 (depression). 8. Recent history or current evidence of drug abuse or alcoholism.

1. stato di malattia avanzato o con discinesie gravi 2. presenza nella storia clinica dei tre mesi precedenti di malattie significative o non ben controllate farmacologicamente, di natura pschiatrica, ematologica, renale, epatica, endocrinologica, neurologica (oltre il Parkinson), cardiovascolare o tumori in fase attiva. 3. ogni parametro clinico che risulti significativo allo screening al giudizio dello sperimentatore. 4. storia recente di ipotensione o svenimenti 5. demenza 6. disturbi del comportamento o amputazioni di arti che precludano la valutazione clinica 7. sogetti con storia di psicosi significative 8. storia recente di abuso di sostanze o alcool

E.5 End points

E.5.1

Primary end point(s)

• Change from baseline in absolute awake time spent “off”

Riduzione delle ore di OFF e del wearing-off

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline and after 2 months

Baseline e dopo 2 mesi

E.5.2

Secondary end point(s)

Valutazione e modifica delle scale: UPDRS II e III, Scale del sonno PDSS, CGI del miglioramento, effetti collaterali

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline and after 2 months

Baseline e dopo 2 mesi

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

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.8.4.1

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

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

LVLS

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

Number of subjects for this age range:

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.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.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)

more efficacy therapy for the patient

Scelta del farmaco più eggicace

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

2009-01-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-12-18

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

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