Clinical Trials Register

Summary
EudraCT Number:	2017-002426-20
Sponsor's Protocol Code Number:	Z7219M01
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:	2018-11-26
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

France - ANSM

A.2

EudraCT number

2017-002426-20

A.3

Full title of the trial

A randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of safinamide 100 mg once daily, as add-on therapy, in idiopathic Parkinson’s Disease (IPD) patients with motor fluctuations and PD related chronic pain

A.3.1

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

Effect of Safinamide on Parkinson’s Disease Related Chronic Pain

A.3.2

Name or abbreviated title of the trial where available

Pain study

A.4.1

Sponsor's protocol code number

Z7219M01

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	Zambon SpA
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	Zambon 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	Zambon SpA
B.5.2	Functional name of contact point	Luca Raiteri
B.5.3	Address:
B.5.3.1	Street Address	Via Lillo de Duca 10
B.5.3.2	Town/ city	Bresso, Milan
B.5.3.3	Post code	20091
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390266524624
B.5.6	E-mail	clinicaltrials@zambongroup.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	Xadago
D.2.1.1.2	Name of the Marketing Authorisation holder	Zambon SpA
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Xadago
D.3.4	Pharmaceutical form	Film-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	Safinamide methansulfonate
D.3.9.1	CAS number	202825-46-5
D.3.9.3	Other descriptive name	SAFINAMIDE METHANESULFONATE
D.3.9.4	EV Substance Code	SUB130363
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	50
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	Yes
D.2.1.1.1	Trade name	Xadago
D.2.1.1.2	Name of the Marketing Authorisation holder	Zambon SpA
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Xadago
D.3.4	Pharmaceutical form	Film-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	Safinamide methansulfonate
D.3.9.1	CAS number	202825-46-5
D.3.9.3	Other descriptive name	SAFINAMIDE METHANESULFONATE
D.3.9.4	EV Substance Code	SUB130363
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	100
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated 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

Idiopathic Parkinson's Disease, Hoehn and Yahr stage between 2-3 inclusive during the “ON” phase, experiencing motor fluctuations while on stable doses of L-Dopa (with or without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor) and may be on stable doses of other PD medications (a dopamine agonist, an anticholinergic and/or amantadine), yet are experiencing more than 2 hours of OFF time per day and chronic PD related pain.

E.1.1.1

Medical condition in easily understood language

chronic pain in PD patients, experiencing motor fluctuations while on stable doses of L-dopa

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	LLT
E.1.2	Classification code	10013113
E.1.2	Term	Disease Parkinson's
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the potential efficacy of safinamide 100 mg once daily, compared to placebo, as add-on therapy, for PD related chronic pain

E.2.2

Secondary objectives of the trial

- The percentage of pain responders
- Clinical Global Impression for pain
- Patient Global Impression for pain
- Reduction of pain drugs
- Mood
- Dyskinesia
- Safety & Tolerability

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participant must be 30 years of age or older, at the time of signing the informed consent.
2. Diagnosed with IPD by using the United Kingdom Parkinson’s Disease Society Brain Bank criteria for more than 5 years duration.
3. Receiving treatment with a stable dose of oral L-Dopa (including controlled release [CR], immediate release [IR] or a combination of CR/IR), with and without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of a dopamine agonist, an anticholinergic and/or amantadine for at least 4 weeks prior to the randomisation (baseline visit).
4. Hoehn and Yahr stage between 2-3 (inclusive) during the “ON” phase at the screening visit.
5. Experiencing motor fluctuations following optimum titration of treatment medications and within the 4 weeks immediately prior to randomisation.
6. Experiencing a minimum of 2.0 hours/day of “OFF” time during the day (excluding morning akinesia).
7. Experiencing chronic pain (i.e. ongoing for ≥3 months prior to screening visit); the Investigator must consider chronic pain directly related to PD and not explained by any other health problem (e.g. peripheral neuropathy, organ disease or arthritis pain) OR consider the intensity of chronic pain specifically aggravated by PD.
8. On a stable treatment regimen of analgesics in the 4 weeks prior to the randomisation visit.
9. Able to maintain an accurate and complete electronic diary with the help of a caregiver.
10. Male or female
a. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 4), not breastfeeding, and at least one of the following conditions applies:
i. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4
or
ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4.
11. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
1. Any form of Parkinsonism other than IPD.
2. Diagnosis of chronic migraine (>15 days per month) or cancer pain.
3. History of bipolar disorder, depression, schizophrenia or other psychotic disorder requiring treatment with neuroleptics.
4. History of dementia or cognitive dysfunction.
5. Severe, peak dose or biphasic dyskinesia.
6. Unpredictable or widely swinging fluctuations.
7. Ophthalmologic history including any of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease.
8. Moderate or severe liver failure using the Child-Pugh classification score.
9. History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders.
10. Allergy/sensitivity or contraindications to the IMPs or their excipients, anticonvulsants, L-dopa or other anti-Parkinsonian drugs.
Prior/Concomitant Therapy
11. Treatment with monoamine oxidase inhibitors (MAOIs), levodopa infusion, pethidine, fluoxetine, fluvoxamine less than 4 weeks prior to the randomisation visit.
12. Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest, or participation in a previous trial with safinamide or previous treatment with safinamide.
13. Mini-Mental State Exam (MMSE) total score <24 at screening.
14. NRS score ≤ 4 points at randomization visit.
15. Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for participants while in the study.

E.5 End points

E.5.1

Primary end point(s)

The change from baseline to week 16 in pain severity (“average worst pain experienced in the last 7 days”), as assessed by an 11-point Numerical Rating Scale (NRS).

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1, Day 112

E.5.2

Secondary end point(s)

- Participants with reduction in pain severity of ≥2 points (“average worst pain experienced in the last 7 days”), at week 16 as assessed by an 11-point NRS, compared to baseline.
- The CGI-S score for pain at week 16.
- The change from baseline to week 16 in the CGI-C score for pain.
- The change from baseline to week 16 in the PGI-C score for pain.
- The percentage of reduction in number of concomitant pain drugs from baseline to week 16.
- Descriptive Safety & Tolerability
- The number of patients with at least one intake of PRN pain medication.
Amount of PRN pain medications.
- The change from baseline to week 16 in the HADS score.
- The change from baseline to week 16 in the MDS-UPDRS (total score and subscores) during the “ON” phase.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 1, Day 28, Day 56, Day 112

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

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

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:

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.4.2

For a multinational trial

F.4.2.1

In the EEA

177

F.4.2.2

In the whole clinical trial

177

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)

Subject will be released into local standard of care.

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	FCRIN NS-Park Network
G.4.3.4	Network Country	France

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-12-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-05-03

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