Effects of Safinamide Versus Placebo on Pain in Patients with Parkinson’s Disease with Motor Fluctuations: a Randomized, Controlled, Double-Blind Clinical Trial. Protocol Code: Save Pain 2025

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-08-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Zambon S.p.A

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To investigate the superiority of safinamide compared with placebo in reducing PD-related pain

Secondary objectives 1

1. To investigate the superiority of safinamide compared with placebo in reducing PD-related pain, PD motor symptoms and complications, other non-motor symptoms

Conditions and MedDRA coding

PARKINSON’S DISEASE WITH MOTOR FLUCTUATIONS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18 years PD-related chronic pain (lasting more than 3 months) and motor fluctuations while receiving stable doses of L-dopa (alone or with other dopaminergic treatments) for at least 4 weeks prior to baseline (visit T0)
2. If female, participants must either be post-menopausal for at least one year, as self-reported by the patient, or, if of childbearing potential, must have a negative plasma human chorionic gonadotropin (HCG) test to exclude pregnancy, at screening. Additionally, if of childbearing potential, patients will be required to undergo monthly urine pregnancy testing, scheduled at approximately day 30 and day 60, and the urine test at the final visit (T1). Moreover, women of childbearing potential must agree to use a highly effective method of contraception, starting 2 months before the enrollment, throughout the entire duration of the study and for at least 30 days after the last dose of the study medication.
3. Diagnosis of PD according to the International Parkinson and Movement Disorders Society (MDS) clinical diagnostic criteria.(Postuma et al., 2015)
4. Disease duration since diagnosis of ≥ 3 years
5. Presence of motor fluctuations (> 1.5 hours OFF time/day excluding morning akinesia)
6. Hoehn and Yahr stage II–III during ON time
7. A history of pain symptoms for the last 12 weeks [at least 4 points scored on the Numerical Rating Scale (NRS)]
8. Willing to participate in this study and able to understand and sign the written informed consent and the form privacy data
9. Be on stable daily doses of oral L-dopa (including controlled release [CR], immediate release [IR] or a combination of CR/IR), with and without benserazide/carbidopa, and optionally with a catechol-O-methyltransferase (COMT) inhibitor. Participants may also be receiving stable doses of dopamine agonists, anticholinergics and/or amantadine for at least 4 weeks prior to the screening visit
10. Participants must be able to speak and understand the Italian language
11. Be responsive to levodopa as per the MDS Clinical Diagnostic Criteria for Parkinson’s disease (Postuma et al., 2015), which define responsiveness as a clinically meaningful benefit to dopaminergic therapy, either documented objectively or subjectively

Exclusion criteria 21

1. Concomitant therapy with monoamine oxidase B inhibitors
2. Patients experiencing severe, disabling peak-dose or biphasic dyskinesia, or unpredictable or widely swinging symptom fluctuations
3. De novo patients
4. Evidence of dementia suggested by a Mini-Mental Scale Examination (MMSE) score < 24
5. Evidence of depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, DSM V.(Roehr, 2013)
6. Treatment with antidepressant medications
7. Signs and symptoms suggestive of atypical parkinsonism
8. Severe and progressive medical illnesses other than PD
9. Concomitant diseases potentially causing acute or chronic pain (i.e., rheumatologic conditions, cancer, severe polyneuropathy, and spine injuries
10. Treatment with opioids, neuroleptics, barbiturates, phenothiazines, pregabalin, gabapentin
11. Any other contraindication according to the current Summary of product characteristics (SmPC) of safinamide
12. Previous neurosurgical intervention or stereotactic brain surgery for PD
13. Concomitant infusive device-aided therapies for PD
14. Drug and/or alcohol abuse within 12 months prior to the screening visit.
15. Use of any investigational drug or device within 30 days prior to screening or 5 half-lives (whichever is the longest), or at any point during the study.
16. Known allergy, sensitivity, or contraindications to the investigational medicinal products (IMPs), their excipients
17. Any clinically significant condition which, in the opinion of the Investigator, would be incompatible with study participation or pose a risk to the patient during the study
18. Moderate to severe liver failure as defined by the Child-Pugh classification score, or human immunodeficiency virus (HIV) infection
19. Treatment with monoamine oxidase inhibitors (MAOIs), pethidine, opiates, opioids, fluoxetine, fluvoxamine within 4 weeks prior to the screening visit. These drugs are not allowed throughout the study and up 2 weeks after the last dose of study drug.
20. History of ophthalmologic conditions including any of the following: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease.
21. Pregnancy and breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. We could hypothesize a mean change of NRS difference between the experimental (safinamide) and the control group (placebo) of 1.6 points on NRS in favor of the experimental group after 12 weeks of treatment

Secondary endpoints 1

1. We hypothesize that the safinamide group will demonstrate a greater mean improvement compared to the placebo group across several secondary outcome measures. The expected between-group difference for UPDRS Part III and PDQ-39 is estimated to range from –0.9 to –2.3 points and –16.5 to – 18.6 points, respectively. For KPPS, BPI (intensity and interference), and UPDRS Part IV it is not possible to estimate a between-group difference.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera Universitaria Integrata Verona

Sponsor organisation

Azienda Ospedaliera Universitaria Integrata Verona

Address

Piazzale Ludovico Antonio Scuro 10

City

Verona

Postcode

37134

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Michele Tinazzi

Public contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Michele Tinazzi

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications