Safinamide vs Placebo for Pain in Patients With Parkinson's Disease and Motor Fluctuations

Prior treatment

• Concomitant therapy with monoamine oxidase B inhibitors.
• Treatment with antidepressant medications.
• 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.
• 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.
• 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.

Other illness

• 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.3.
• Severe and progressive medical illnesses other than PD.
• 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.
• 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.

Other

• Patients experiencing severe, disabling peak-dose or biphasic dyskinesia, or unpredictable or widely swinging symptom fluctuations.
• De novo patients.
• Signs and symptoms suggestive of atypical parkinsonism.
• Any other contraindication according to the current Summary of product characteristics (SmPC) of safinamide.
• Pregnancy and breastfeeding.

• 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).
• Diagnosis of PD according to the International Parkinson and Movement Disorders Society (MDS) clinical diagnostic criteria.
• 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 responsive to levodopa as per the MDS Clinical Diagnostic Criteria for Parkinson's disease, which define responsiveness as a clinically meaningful benefit to dopaminergic therapy, either documented objectively or subjectively.
• 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.
• 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 enrollment, throughout the entire duration of the study and for at least 30 days after the last dose of the study medication. Acceptable methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence \[Sexual abstinence is considered an acceptable method only if it reflects the participant's consistent and preferred lifestyle.\].