Evaluation of Safinamide Versus Placebo on Pain Management in Parkinson's Disease Patients with Motor Fluctuations: A Randomized, Double-Blind Trial
- Trial ID
- 2025-521512-20-00
- Protocol
- SAVE PAIN 2025
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **superiority** of safinamide compared with placebo in reducing pain associated with **Parkinson's disease** with motor fluctuations. This is clinically relevant as pain is a significant non-motor symptom that affects the quality of life in patients with Parkinson's disease, and effective management of this symptom can lead to improved patient outcomes.
Secondary objectives include investigating the superiority of safinamide over placebo in reducing Parkinson's disease-related motor symptoms and complications, as well as other non-motor symptoms. These objectives are important for understanding the broader therapeutic potential of safinamide in managing both motor and non-motor symptoms of Parkinson's disease, which can contribute to a comprehensive treatment approach.
Participants
The clinical trial involves participants diagnosed with **Parkinson's disease with motor fluctuations**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a history of Parkinson's disease for at least three years, with motor fluctuations and chronic pain persisting for more than three months. All participants must be on stable doses of L-dopa, with or without additional dopaminergic treatments, for at least four weeks prior to the baseline visit. The trial does not include a vulnerable population. Participants must be responsive to levodopa and meet the International Parkinson and Movement Disorders Society clinical diagnostic criteria. The sponsor has not provided the total number of participants involved in the study. Key lifestyle considerations include the ability to speak and understand the Italian language, and for females of childbearing potential, adherence to specific contraceptive measures and pregnancy testing protocols. The trial population was selected based on these criteria to ensure the reliability and validity of the study outcomes.
Plans and Procedures
The clinical trial is designed to evaluate the **effects of safinamide** versus placebo on pain in patients with **Parkinson's disease** with motor fluctuations. This study is a randomized, controlled, double-blind trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence recruitment in October 2025 and conclude by October 2027, with a total duration of approximately two years.
Participants will be involved in the study for a maximum of 12 weeks. The trial will begin with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, language proficiency, and disease characteristics. Following successful screening, participants will be randomized to receive either safinamide or a placebo. The investigational medicinal products include Xadago 50 mg and 100 mg film-coated tablets, with corresponding placebo formulations. The primary endpoint is the mean change in the Numerical Rating Scale (NRS) for pain, hypothesized to show a 1.6-point difference favoring the safinamide group after 12 weeks of treatment.
Study visits will be scheduled at baseline (T0), approximately day 30, day 60, and at the end of the study (T1). These visits will include assessments of pain, motor function, and other relevant clinical parameters. Female participants of childbearing potential will undergo monthly urine pregnancy testing to ensure safety. The trial will also evaluate secondary endpoints, including improvements in the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39).
Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial is conducted under strict ethical guidelines, with informed consent obtained from all participants. The study aims to provide valuable insights into the management of pain in Parkinson's disease, potentially leading to improved therapeutic strategies.
Treatment
The clinical trial involves the administration of **Xadago 50 mg film-coated tablets**, which contain the active substance **safinamide**. These tablets are administered orally and are designed for chemical drug use. The maximum daily dose is 50 mg, with a total dose not exceeding 50 mg per day. The treatment period for this dosage is limited to 1 week. The tablets are identical to the marketed batch up to the primary packaging, with modifications in secondary packaging and labeling to ensure blinding during the trial.
Another experimental treatment in the trial is **Xadago 100 mg film-coated tablets**, also containing the active substance safinamide. These tablets are administered orally, with a maximum daily dose of 100 mg and a total dose not exceeding 100 mg per day. The treatment period for this dosage extends up to 11 weeks. Similar to the 50 mg tablets, the 100 mg tablets are identical to the marketed batch up to the primary packaging, with modifications in secondary packaging and labeling to maintain blinding.
The trial also includes the use of **Safinamide 50 mg PLACEBO** film-coated tablets. These placebo tablets have the same composition as the investigational medicinal products, except for the absence of the active substance safinamide methanesulfonate. The missing active substance is replaced with an equivalent amount of microcrystalline cellulose, an excipient present in the authorized formulation. The placebo is used to maintain the double-blind nature of the trial.
Similarly, **Safinamide 100 mg PLACEBO** film-coated tablets are used in the trial. These placebo tablets are identical in composition to the investigational medicinal products, except for the absence of the active substance safinamide methanesulfonate. The missing active substance is substituted with microcrystalline cellulose, ensuring consistency with the authorized formulation. The placebo serves to uphold the double-blind design of the study.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the impact of **safinamide** on pain in patients with Parkinson's disease experiencing motor fluctuations. The primary endpoint is the mean change in the Numerical Rating Scale (NRS) score, with an anticipated difference of 1.6 points favoring the experimental group (safinamide) over the control group (placebo) after 12 weeks of treatment. Secondary endpoints include the assessment of several outcome measures such as the Unified Parkinson's Disease Rating Scale (UPDRS) Part III, Parkinson's Disease Questionnaire (PDQ-39), King's Parkinson's Disease Pain Scale (KPPS), and the Brief Pain Inventory (BPI) for intensity and interference, as well as UPDRS Part IV. The expected between-group differences for UPDRS Part III and PDQ-39 are estimated to range from -0.9 to -2.3 points and -16.5 to -18.6 points, respectively. However, it is not possible to estimate a between-group difference for KPPS, BPI, and UPDRS Part IV.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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)
- 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.
- Diagnosis of PD according to the International Parkinson and Movement Disorders Society (MDS) clinical diagnostic criteria.(Postuma et al., 2015)
- Disease duration since diagnosis of ≥ 3 years
- Presence of motor fluctuations (> 1.5 hours OFF time/day excluding morning akinesia)
- Hoehn and Yahr stage II–III during ON time
- A history of pain symptoms for the last 12 weeks [at least 4 points scored on the Numerical Rating Scale (NRS)]
- Willing to participate in this study and able to understand and sign the written informed consent and the form privacy data
- 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
- Participants must be able to speak and understand the Italian language
- 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
- Concomitant therapy with monoamine oxidase B inhibitors
- Patients experiencing severe, disabling peak-dose or biphasic dyskinesia, or unpredictable or widely swinging symptom fluctuations
- De novo patients
- Evidence of dementia suggested by a Mini-Mental Scale Examination (MMSE) score < 24
- Evidence of depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, DSM V.(Roehr, 2013)
- Treatment with antidepressant medications
- Signs and symptoms suggestive of atypical parkinsonism
- Severe and progressive medical illnesses other than PD
- Concomitant diseases potentially causing acute or chronic pain (i.e., rheumatologic conditions, cancer, severe polyneuropathy, and spine injuries
- Treatment with opioids, neuroleptics, barbiturates, phenothiazines, pregabalin, gabapentin
- Any other contraindication according to the current Summary of product characteristics (SmPC) of safinamide
- Previous neurosurgical intervention or stereotactic brain surgery for PD
- Concomitant infusive device-aided therapies for PD
- Drug and/or alcohol abuse within 12 months prior to the screening visit.
- 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.
- Known allergy, sensitivity, or contraindications to the investigational medicinal products (IMPs), their excipients
- 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
- Moderate to severe liver failure as defined by the Child-Pugh classification score, or human immunodeficiency virus (HIV) infection
- 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.
- 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.
- Pregnancy and breastfeeding
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 01 Oct 2025 | 60 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Safinamide 100 mg PLACEBO:
Safinamide 100 mg PLACEBO film-coated tablets have the same composition as the relevant Investigational Medicinal Products except for the presence of Active Substance that is missing in the placebo formulations. The missing amount of active substance Safinamide methanesulfonate is replaced in the PLACEBO formulation with the same amount of Microcrystalline cellulose, one of the excipients already present in the authorised formulation | Placebo | N/A | — | — | — | N/A |
Xadago 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 100 | 11 | PRD2441349 |
Xadago 50 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 50 | 1 | PRD2440731 |
Safinamide 50 mg PLACEBO:
Safinamide 50 mg, PLACEBO film-coated tablets have the same composition as the relevant
Investigational Medicinal Products except for the presence of Active Substance that is missing in the
placebo formulations. The missing amount of active substance Safinamide methanesulfonate is
replaced in the PLACEBO formulation with the same amount of Microcrystalline cellulose, one of the
excipients already present in the authorised formulation. | Placebo | N/A | — | — | — | N/A |