Effect of Safinamide on Parkinson's Disease Related Chronic Pain

A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Safinamide 100mg Once Daily, as add-on Therapy, in Idiopathic Parkinson's Disease (PD) Patients With Motor Fluctuations and PD Related Chronic Pain

Primary objective:

• To evaluate the potential efficacy of safinamide 100 mg once daily (OD), compared with placebo, as add-on therapy for PD-related chronic pain

Secondary objectives:

• Percentage of pain responders
• Clinical Global Impression for pain
• Patient Global Impression for pain
• Reduction in use of pain drugs
• Mood
• Motor and non-motor symptoms

Safety Objectives:

• Safety and tolerability

This is a Phase IV, international, multicentre, randomised, double-blind, placebo controlled study in idiopathic Parkinson's disease (IPD) patients, experiencing motor fluctuations and PD-related chronic pain while on stable doses of levodopa (L-Dopa), to Evaluate the Efficacy and Safety of Safinamide 100 mg Once Daily, as Add-On Therapy.

The study consisted of:

• A screening period of up to 1 to 2 weeks.
• A treatment period of 16 weeks.
• A telephone follow-up call at 1 week after the end of treatment. Eligible subjects were randomly assigned in a ratio of 2:1 to receive either safinamide (50 mg or 100 mg) or matching placebo. At Day 1, eligible subjects entered the treatment period to receive safinamide 50 mg (from Day 1 to Day 7) and then 100 mg (from Day 8 onwards) orally OD. After completion of all baseline assessments, subjects received the first dose of study drug at the study center and, thereafter, study drug was to be taken at home each morning along with their first morning dose of L-DOPA and other (if any) PD medications. On Day 8, the dose of study drug was increased, at home, to 100 mg OD. Each subject received treatment for 16 weeks, with visits at Week 0/Day 1 (baseline) and at Weeks 4, 8, and 16 (or early termination). From Day 1 onwards, subjects recorded the use of as-needed (PRN) medications along with indicating the worst pain they experienced on a daily basis.

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 participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i.Not a woman of childbearing potential (WOCBP) OR ii.A WOCBP who agrees to follow the contraceptive guidance

10. Capable of giving signed informed consent

Exclusion Criteria:

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.
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