Safinamide for Parkinson's disease with motor fluctuations

Inclusion criteria

• {"criterion_text":"- 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)"}
• {"criterion_text":"- Participants must be able to speak and understand the Italian language"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Diagnosis of PD according to the International Parkinson and Movement Disorders Society (MDS) clinical diagnostic criteria.(Postuma et al., 2015)"}
• {"criterion_text":"- Disease duration since diagnosis of ≥ 3 years"}
• {"criterion_text":"- Presence of motor fluctuations (> 1.5 hours OFF time/day excluding morning akinesia)"}
• {"criterion_text":"- Hoehn and Yahr stage II–III during ON time"}
• {"criterion_text":"- A history of pain symptoms for the last 12 weeks [at least 4 points scored on the Numerical Rating Scale (NRS)]"}
• {"criterion_text":"- Willing to participate in this study and able to understand and sign the written informed consent and the form privacy data"}
• {"criterion_text":"- 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"}

Exclusion criteria

• {"criterion_text":"- Concomitant therapy with monoamine oxidase B inhibitors"}
• {"criterion_text":"- Treatment with opioids, neuroleptics, barbiturates, phenothiazines, pregabalin, gabapentin"}
• {"criterion_text":"- Any other contraindication according to the current Summary of product characteristics (SmPC) of safinamide"}
• {"criterion_text":"- Previous neurosurgical intervention or stereotactic brain surgery for PD"}
• {"criterion_text":"- Concomitant infusive device-aided therapies for PD"}
• {"criterion_text":"- Drug and/or alcohol abuse within 12 months prior to the screening visit."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Known allergy, sensitivity, or contraindications to the investigational medicinal products (IMPs), their excipients"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Moderate to severe liver failure as defined by the Child-Pugh classification score, or human immunodeficiency virus (HIV) infection"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients experiencing severe, disabling peak-dose or biphasic dyskinesia, or unpredictable or widely swinging symptom fluctuations"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Pregnancy and breastfeeding"}
• {"criterion_text":"- De novo patients"}
• {"criterion_text":"- Evidence of dementia suggested by a Mini-Mental Scale Examination (MMSE) score < 24"}
• {"criterion_text":"- Evidence of depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, DSM V.(Roehr, 2013)"}
• {"criterion_text":"- Treatment with antidepressant medications"}
• {"criterion_text":"- Signs and symptoms suggestive of atypical parkinsonism"}
• {"criterion_text":"- Severe and progressive medical illnesses other than PD"}
• {"criterion_text":"- Concomitant diseases potentially causing acute or chronic pain (i.e., rheumatologic conditions, cancer, severe polyneuropathy, and spine injuries"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in Numerical Rating Scale (NRS) pain score at 12 weeks; between-group mean difference (hypothesized 1.6 points in favor of safinamide)."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Between-group differences measured using UPDRS Part III, PDQ-39, KPPS, Brief Pain Inventory (BPI) intensity and interference, and UPDRS Part IV; expected ranges provided for UPDRS III and PDQ-39; other scales to be compared descriptively."}

Italy

Earliest CTIS Part Ii Submission Date

14-07-2025

Latest Decision Or Authorization Date

16-10-2025

Processing Time Days

94

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

Azienda Ospedaliera Universitaria Integrata Verona

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Zambon S.p.A","duties_or_roles":"Source of monetary support","organisation_type":""}