Effect of Safinamide on Parkinson’s Disease Related Chronic Pain

• Register: EUCTR
• Last refreshed on: 12 July 2021
• Main ID: EUCTR2017-002426-20-AT
• Date of registration: 03/12/2018
• Prospective Registration: Yes
• Primary sponsor: Zambon SpA
• Public title: Effect of Safinamide on Parkinson’s Disease Related Chronic Pain
• Scientific title: 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 - Pain study
• Date of first enrolment: 22/01/2019
• Target sample size: 105
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002426-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Austria, Spain

Contacts

• Name: Elena Tiberio
• Affiliation: Zambon SpA

• Name: Elena Tiberio
• Affiliation: Zambon SpA

Key inclusion & exclusion criteria

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 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.
7. If taking regular analgesics, the treatment regimen should be stable
in the 4 weeks prior to the randomisation visit.
8. Able to maintain an accurate and complete electronic diary with the
help of a caregiver.
9. 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.
10. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

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, intolerance or contraindications to Safinamide.
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.
13. Previous treatment with Safinamide in the 9 months before the screening visit
14. Mini-Mental State Exam (MMSE) total score <24 at screening.
15. NRS score = 4 points at randomization visit.
16. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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.
MedDRA version: 21.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 100000004852

Intervention(s)

Trade Name: Xadago
Product Name: Xadago
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Safinamide methansulfonate
CAS Number: 202825-46-5
Other descriptive name: SAFINAMIDE METHANESULFONATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Xadago
Product Name: Xadago
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Safinamide methansulfonate
CAS Number: 202825-46-5
Other descriptive name: SAFINAMIDE METHANESULFONATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 1, Day 112

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

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

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).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 1, Day 28, Day 56, Day 112

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.

Secondary ID(s)

2017-002426-20-ES

Z7219M01

Source(s) of Monetary Support

Zambon SpA

Ethics review

Status: Approved
Approval date: 22/01/2019
Contact: