Clinical Trials Register

Summary
EudraCT Number:	2014-005562-30
Sponsor's Protocol Code Number:	CITIPARK
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-005562-30

A.3

Full title of the trial

Role of citicoline as supportive therapy in Parkinson’s disease.

Ruolo della citicolina nella terapia di supporto nella malattia di Parkinson.

A.3.1

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

Citicoline as supportive treatment in Parkinson's disease

La citicolina nel trattamento di sostegno alla malattia di Parkinson

A.3.2

Name or abbreviated title of the trial where available

CITIPARK

A.4.1

Sponsor's protocol code number

CITIPARK

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	PIAM FARMACEUTICI S.P.A.
B.1.3.4	Country	Italy
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	PIAM farmaceutici S.p.A.
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	PIAM FARMACEUTICI S.P.A.
B.5.2	Functional name of contact point	Dr Marco Terrile
B.5.3	Address:
B.5.3.1	Street Address	via Fieschi 8/7
B.5.3.2	Town/ city	Genova
B.5.3.3	Post code	16121
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39010518621
B.5.5	Fax number	+39010355734
B.5.6	E-mail	terrile@piamfarmaceutici.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	CITICOLIN*1G/4ML IM IV 5 F
D.2.1.1.2	Name of the Marketing Authorisation holder	PIAM FARMACEUTICI S.P.A.
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.3.1	Product name	Citicolina 1000 mg/die
D.3.2	Product code	[citicolin]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CITICOLINA SODICA
D.3.9.1	CAS number	33818-15-4
D.3.9.2	Current sponsor code	Citicolina sale sodico
D.3.9.4	EV Substance Code	PRD580267
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	1045
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

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

neurodegenerative disease

malattia degenerativa del sistema nervoso

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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029205
E.1.2	Term	Nervous system disorders
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 primary objective of this post-authorization study is to confirm the clinical efficacy in patients with Parkinson’s disease and treated with dopaminergic therapy after a treatment period of six months with citicoline.

L’obiettivo primario di questo studio post-autorizzativo è confermare l’efficacia clinica della terapia dopo 6 mesi di trattamento con citicolina in pazienti affetti da malattia di Parkinson trattati con terapia dopaminergica.

E.2.2

Secondary objectives of the trial

Secondary objectives
- To demonstrate the efficacy of citicoline in improving the quality of life;
- To demonstrate the efficacy of citicoline on both motor and non-motor symptoms of Parkinson’s disease in patients treated with dopaminergic therapy;
- To assess the safety of citicoline in patients treated with dopaminergic therapy.

Gli obiettivi secondari di questo studio sono:
- dimostrare l’efficacia della citicolina nel miglioramento della qualità della vita;
- dimostrare l’efficacia della citicolina sui sintomi motori e non-motori della malattia di Parkinson in pazienti trattati con terapia dopaminergica;
- valutare la sicurezza della citicolina in pazienti trattati con terapia dopaminergica.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Outpatients of both genders older than 60 years and with Parkinson’s disease;
2. Disease stage between 1.5 and 3 of the Hoehn and Yahr scale;
3. Stable therapy with Levodopa in the 4 week prior to V0; the maximum daily dosage allowed is 2 g/day in accordance with the standard guidelines;
4. Stability of therapy with other dopaminergic or other anti-Parkinson drugs (e.g. DA/L Dopa, COMT inhibitors, Rasagiline, etc.) in the 4 week prior toV0; the dosage of these medications must be within the maximum daily dosage allowed in accordance with the guidelines.
5. A stable disease without motor fluctuations in the 4 weeks prior to V0.

1. Pazienti ambulatoriali di entrambi i sessi affetti da malattia di Parkinson e di età > 60 anni.
2. Stadio della malattia compreso tra 1.5 e 3 alla scala di Hoehn and Yahr.
3. Stabilità della terapia con levodopa nelle 4 settimane antecedenti V0. Il dosaggio giornaliero massimo consentito, secondo le linee guida standard, è di 2 g/die.
4. Stabilità della terapia con altri eventuali dopaminergici o altri farmaci anti-Parkinson (es. DA/L-Dopa, inibitori COMT, rasagilina ecc.) nelle 4 settimane antecedenti V0. Verranno consentiti dosaggi entro i limiti giornalieri massimi consentiti secondo le linee guida (si veda paragrafo 8.5)
5. Stabilità del quadro clinico in assenza di fluttuazioni motorie nelle 4 settimane antecedenti V0.

E.4

Principal exclusion criteria

1. Presence of ON-OFF phenomenon and dyskinesias;
2. Presence of any degenerative pathology different from Parkinson’s disease (whose effects may generate confounding on the study’s outcomes);
3. Presence of any dementia (according to the DSM-IV) which might make the patient unable to follow the study’s procedures (e.g. questionnaire or self-assessment scales);
4. Bleeding diathesis caused by any pathology (e.g liver cirrhosis) or treatment with anticoagulants and/or antiplatelet medications, which would contraindicate the chronic treatment with injectable medications.
5. Unstable treatment with cholinergic medications (either cholinomimetics or anticholinergic) since at least 3 months prior to the inclusion into the study;

1. Presenza di fenomeno ON-OFF e discinesie
2. Presenza di una qualsiasi patologia degenerativa diversa dalla malattia di Parkinson (i cui effetti potrebbero essere confondenti sui risultati dello studio)
3. Presenza di un qualsiasi tipo di demenza (secondo il DSM-IV), che potrebbe rendere il paziente impossibilitato a rispettare le procedure dello studio (es. questionari o scale di autovalutazione)
4. Diatesi emorragica, causata da qualunque patologia (es. cirrosi epatica), o trattamento con farmaci anticoagulanti e/o antiaggreganti, che potrebbero controindicare il trattamento cronico con farmaci iniettivi.
5. Trattamento con farmaci colinergici (colino-mimetici o anticolinergici), che non siano stabili da almeno 3 mesi antecedenti l'inclusione nello studio.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is defined as the change in the total score of the MDS-UPDRS scale measured at the end of the second cycle (V4,T24) versus baseline (T0) weeks after the treatment starting.

L’end-point primario di efficacia è definito come variazione del punteggio totale della MDS-UPDRS tra il basale (T0) e la fine del secondo ciclo di terapia, 24 settimane dopo l'inizio del trattamento (V4, T24).

E.5.1.1

Timepoint(s) of evaluation of this end point

between baseline (T0) and the end of the second cycle (V4,T24), 24 weeks after treatment starting.

tra il basale (T0) e la fine del secondo ciclo di terapia, 24 settimane dopo l'inizio del trattamento (V4, T24).

E.5.2

Secondary end point(s)

The improvement on the Quality of life (QoL-30), assessed at the end of the second treatment cycle (V4,T24) versus the baseline (T0).; Evaluation of clinical improvement measured with the part II and part III of the CGI scale, assessed at the end of the second treatment cycle (V4,T24) versus baseline (T0).; Changes in the total score and in the sub-scale scores of PDQ39, CGI part I and NMSS scales, at the end of the second treatment cycle (V4,T24) versus baseline(T0).; Changes in the total score and in the sub-scale scores of MDS-UPDRS scale at the end of the treatment period of the first cycle (V1,T6) versus baseline (V0,T0) to assess the short-term effect.; Changes in the total score and in the sub-scale scores of MDS-UPDRS scale at the end of the first cycle (V2,T12) versus baseline (V0,T0), to assess the short-term effect after a discontinuation period.; Changes in the total score and in the sub-scale scores of MDS-UPDRS scale between the end of treatment on the first cycle (V1,T6) and the end of the first cycle itself (V2,T12), to assess the effect maintenance after 6 weeks of discontinuation.; Changes in the total score and in the sub-scale scores of MDS-UPDRS scale at the end of treatment on the second cycle (V3,T18) versus baseline (T0), to assess the immediate effect at the treatment end.; Changes in the total score and in sub-scale scores of MDS-UPDRS scale between the end of treatment on the second cycle (V3,T18) and the end of second cycle itself (V4,T24), to assess the effect maintenance after 6 weeks of discontinuation.

Il miglioramento rispetto al basale della qualità della vita (QoL-30), valutato al termine del secondo (V4, T24) ciclo di trattamento rispetto al basale (T0).; La valutazione del miglioramento clinico alla scala CGI parte II e parte III, valutato al termine del secondo (V4, T24) ciclo di trattamento, rispetto al basale (T0).; Le variazioni rispetto al basale (T0) del punteggio totale e dei punteggi delle sottoscale di PDQ39, CGI parte I e NMSS, valutati alla fine del secondo (V4, T24) ciclo di trattamento.; Variazione del punteggio totale e dei punteggi delle sottoscale di MDS-UPDRS tra il basale (V0, T0) e la fine del trattamento nel primo ciclo di trattamento (V1, T6), per valutare l'effetto a breve termine.; Variazione del punteggio totale e dei punteggi delle sottoscale di MDS-UPDRS tra il basale (T0) e la fine del primo ciclo di trattamento (V2, T12), per valutare l'effetto a breve termine, ma dopo un periodo di sospensione.; variazione del punteggio totale e dei punteggi delle sottoscale di MDS-UPDRS tra la fine del trattamento durante il primo ciclo (V1, T6) e la fine del primo ciclo stesso (V2, T12), per valutare il mantenimento dell'effetto dopo 6 settimane di interruzione.; Variazione del punteggio totale e dei punteggi delle sottoscale di MDS-UPDRS tra il basale (T0) e la fine del trattamento durante il secondo ciclo (V3, T18), per valutare l'effetto immediato al termine del trattamento; Variazione del punteggio totale e dei punteggi delle sottoscale di MDS-UPDRS tra la fine del trattamento durante il secondo ciclo (V3, T18) e la fine del secondo ciclo stesso (V4, T24), per valutare il mantenimento dell'effetto dopo 6 settimane di interruzione.

E.5.2.1

Timepoint(s) of evaluation of this end point

assessed at the end of the second treatment cycle (V4,T24) versus the baseline (T0).; assessed at the end of the second treatment cycle (V4,T24) versus baseline (T0).; at the end of the second treatment cycle (V4,T24) versus baseline(T0).; at the end of the treatment period of the first cycle (V1,T6) versus baseline (V0,T0).; at the end of the first cycle (V2,T12) versus baseline (V0,T0).; between the end of treatment on the first cycle (V1,T6) and the end of the first cycle itself (V2,T12).; at the end of treatment on the second cycle (V3,T18) versus baseline (T0).; between the end of treatment on the second cycle (V3,T18) and the end of second cycle itself (V4,T24).

valutato al termine del secondo (V4, T24) ciclo di trattamento rispetto al basale (T0).; valutato al termine del secondo (V4, T24) ciclo di trattamento, rispetto al basale (T0).; valutati alla fine del secondo (V4, T24) ciclo di trattamento.; tra il basale (V0, T0) e la fine del trattamento nel primo ciclo di trattamento (V1, T6).; tra il basale (T0) e la fine del primo ciclo di trattamento (V2, T12).; tra la fine del trattamento durante il primo ciclo (V1, T6) e la fine del primo ciclo stesso (V2, T12).; tra il basale (T0) e la fine del trattamento durante il secondo ciclo (V3, T18).; tra la fine del trattamento durante il secondo ciclo (V3, T18) e la fine del secondo ciclo stesso (V4, T24).

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)

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

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

Yes

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

Information not present in EudraCT

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

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

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

374

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

474

F.4.2

For a multinational trial

F.4.2.1

In the EEA

474

F.4.2.2

In the whole clinical trial

474

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

nessuno

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

2016-04-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-05

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

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