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
Overview
- Phase
- Phase 3
- Intervention
- Safinamide
- Conditions
- Parkinson Disease
- Sponsor
- Zambon SpA
- Enrollment
- 307
- Locations
- 31
- Primary Endpoint
- Change From Baseline to Week 16 in the Mean Total Daily "OFF" Time
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged ≥18 years old.
- •Chinese ethnicity.
- •Able to understand and willing to provide written informed consent.
- •Able to maintain an accurate and complete 24-hour diary with the help of a caregiver.
- •Diagnosis of idiopathic Parkinson's Disease (IPD) using the United Kingdom Parkinson's Disease Society Brain Bank criteria of more than 3 years duration.
- •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.
- •A Hoehn and Yahr stage between 1-4 inclusive during the "ON" phase.
- •Experiencing motor fluctuations with a minimum of 1.5 hours/day of "OFF" time during the day (excluding morning akinesia), based on historical data.
- •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:
- •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;
Exclusion Criteria
- •Any form of Parkinsonism other than IPD.
- •Diagnosis of chronic migraine (\>15 days per month) or cancer pain.
- •L-dopa infusion.
- •Hoehn and Yahr stage 5 during the "ON" phase.
- •If female, pregnancy or breast-feeding.
- •Neurosurgical intervention of PD or stereotactic brain surgery.
- •Severe peak dose or biphasic dyskinesia, unpredictable or widely swinging fluctuations.
- •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.
- •Drug and/or alcohol abuse within 12 months prior to the screening visit.
- •History of dementia or severe cognitive dysfunction.
Arms & Interventions
Safinamide
Patient will receive film-coated Safinamide tablets orally at an initial dose of 50 mg once daily (OD) and then will be increased the day after the Visit 3/week 2 (ideally at day 15) to the final dose of 100 mg OD. Treatment will continue daily for a total of 16 weeks.
Intervention: Safinamide
Placebo
Patient will receive matching placebo orally at an initial dose of 50 mg once daily (OD) and then will be increased the day after the Visit 3/week 2 (ideally at day 15) to the final dose of 100 mg OD. Treatment will continue daily for a total of 16 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline to Week 16 in the Mean Total Daily "OFF" Time
Time Frame: At baseline and Week 16
The mean total daily "OFF" time was assessed by 24-hour patient diary cards, of safinamide 100 mg/day compared to placebo, given as add-on therapy in PD patients with motor fluctuations on stable doses of L-dopa. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period: * "OFF" (Stiffness, marked decrease in mobility, or immobility). * "ON" without dyskinesia (Good or practically normal mobility without dyskinesia). * "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort). * "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself). * Asleep (Time spent asleep).
Secondary Outcomes
- Change From Baseline to Week 16 in Pain Severity, as Assessed by an 11 Point Numerical Rating Scale (NRS)(At baseline and Week 16)
- Change From Baseline to Week 16 in the Mean Total Daily "ON" Time(At baseline and Week 16)
- Change From Baseline to Week 16 in the Mean Daily "ON" Time With no/Non Troublesome Dyskinesia(At baseline and Week 16)
- Clinical Global Impression of Change (CGI-C) Assessed at Week 16(At baseline and Week 16)
- Change From Baseline to Week 16 in the Parkinson's Disease Questionnaire-39 Items (PDQ-39) Score(At baseline and Week 16)
- Change From Baseline to Week 16 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score During the "ON" Phase(At baseline and Week 16)
- Change From Baseline to Week 16 in the UPDRS Part II Activities of Daily Living (ADL) Score During the "ON" Phase(At baseline and Week 16)
- Clinical Global Impression of Severity (CGI-S) Score Assessed at Week 16(At week 16)
- Change From Baseline to Week 16 in the UPDRS Part III (Motor Function) Score During the "ON" Phase(At baseline and Week 16)