A Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson's Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa

A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson's Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa

This is a Phase III, multicentre, randomised, double-blind, placebo-controlled study to evaluate the effects of 100 mg safinamide, administered orally once daily (OD), in Chinese Parkinson's disease (PD) patients, experiencing motor fluctuations while on stable doses of Levodopa (L-dopa) (alone or in combination with other anti-Parkinson drugs). Eligible patients are required to meet the United Kingdom PD Society Brain Bank Clinical Diagnostic Criteria. The study involves a placebo group. Placebo will be added to the standard stabilized treatment as a control of the safinamide group, hence patients on placebo will have benefit from other ongoing anti-PD medication. A total of 306 patients will be randomised into this study (153 in the safinamide and 153 in the placebo groups).

Inclusion Criteria:

1. Male or female patients aged ≥18 years old.

2. Chinese ethnicity.

3. Able to understand and willing to provide written informed consent.

4. Able to maintain an accurate and complete 24-hour diary with the help of a caregiver.

5. Diagnosis of idiopathic Parkinson's Disease (IPD) using the United Kingdom Parkinson's Disease Society Brain Bank criteria of more than 3 years duration.

6. Be levodopa responsive and receiving treatment with stable daily doses of oral L-dopa, with or without benserazide/carbidopa, with or without addition of a catechol-O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of dopamine agonists, anticholinergics and/or amantadine for at least 4 weeks prior to the screening visit.

7. A Hoehn and Yahr stage between 1-4 inclusive during the "ON" phase.

8. Experiencing motor fluctuations with a minimum of 1.5 hours/day of "OFF" time during the day (excluding morning akinesia), based on historical data.

9. If female, be post-menopausal for at least one year or have undergone hysterectomy or, if of child-bearing potential, must have a negative pregnancy test, must not be breast-feeding nor become pregnant during the study and must use adequate contraception for 1 month prior to randomisation and for up to 1 month after the last dose of study drug. Adequate contraception is defined as:

   1. Hormonal oral, implantable, transdermal, or injectable contraceptives or a non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit;
   2. a male sexual partner who agrees to use a male condom with spermicide or a sterile sexual partner . For all women of child-bearing potential, urine pregnancy test result at screening must be negative.

For all women of child-bearing potential, urine pregnancy test result at screening must be negative.

Exclusion Criteria:

1. Any form of Parkinsonism other than IPD.
2. Diagnosis of chronic migraine (>15 days per month) or cancer pain.
3. L-dopa infusion.
4. Hoehn and Yahr stage 5 during the "ON" phase.
5. If female, pregnancy or breast-feeding.
6. Neurosurgical intervention of PD or stereotactic brain surgery.
7. Severe peak dose or biphasic dyskinesia, unpredictable or widely swinging fluctuations.
8. History of major depression or other clinically significant psychotic disorder which compromise the ability to provide the informed consent or to participate to the study.
9. Drug and/or alcohol abuse within 12 months prior to the screening visit.
10. History of dementia or severe cognitive dysfunction.
11. Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest, or during the study.
12. Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, to anticonvulsants or to anti-Parkinson drugs.
13. Any clinically significant condition (including laboratory values) which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for patients while in the study.
14. Moderate or severe liver failure using the Child-Pugh classification score, or human immunodeficiency virus (HIV) infection.
15. Treatment with monoamine oxidase inhibitors (MAOIs), pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 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.
16. 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.