Overnight Switch From Rasagiline To Safinamide

Study Overview
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Brief Summary
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Rasagiline label report the indication to wait at least 14 days between discontinuation of rasagiline and initiation of another MAO inhibitor. This results in a major inconvenience for Parkinsonian patients (PD) due to their clinical worsening. Safinamide is a reversible MAO-B inhibitor, characterized by a good safety profile. In clinical practice safinamide is often introduced instead of rasagiline following an overnight switch. The aim of this study is to explore the safety and tolerability of the immediate switch from rasagiline (irreversible MAO-B inhibitor) to safinamide, with the expectation that there will be no adverse events or increased risk of hypertensive crisis for patients with PD or signs of serotonin syndrome

Detailed Description
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Objective: The aim of this study is to verify safety and tolerability of the immediate switch from rasagiline to safinamide trough monitoring of BP by 24-hour Holter recording. The primary objective of the study will be achieved if the mean BP will not increase by >10 mmHg in the studied population. Methods: This is an open-label, single-centre study conducted at IRCCS San Raffaele Pisana. Study population included patients with idiopathic PD in the mid-late stage of the disease, suffering from motor fluctuation, on stable treatment with rasagiline and Levodopa (alone or in combination with other anti-parkinsonian medication). The protocol contemplates five visits during six weeks, with two 24-hour Holter recording (first in rasagiline and second in first-day of safinamide therapy), monitoring typical symptoms of the serotonin syndrome.

Official Title
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Overnight Switch From Rasagiline To Safinamide In Fluctuating Patients With Parkinson's Disease: A Tolerability And Safety Study

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Safinamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients able to comprehend and provide consent form Patients with idiopathic Parkinson's disease diagnosed according to the UK Brain Bank criteria Patients in mid-to late stage of the disease (Hoehn & Yahr: between the stage 2 and 4 in on state). Patients suffering from motor fluctuations Patients must have a good response to levodopa in the opinion of the investigators (evaluated as improvement ≥ 30% of the UPDRS scores) Stable dosage of antiparkinsonian medication for at least 4 weeks prior to study enrollment Female patients in post-menopausal state; women of childbearing potential must use an acceptable method of contraception Exclusion Criteria: Atypical Parkinsonism Any significant psychiatric, metabolic and systemic concomitant disease Patients with clinically significant out of range laboratory values Patients participating in a clinical trial in the last 6 weeks Patients with moderate-severe cognitive decline not able to provide consent form Patients currently lactating or pregnant or planning to become pregnant during the duration of the study Patients for whom Xadago is contraindicated according to the current SmPC

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safinamide<br>Overnight switch from rasagiline 1 mg OD to safinamide 50 mg OD | Drug: Safinamide<br>* Overnight switch from rasagiline 1 mg OD to safinamide 50 mg OD<br>* Other names: Xadago;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Blood Pressure (BP) | Monitoring of BP by 24-hour Holter (increase by >10 mmHg) | through study completion, an average of 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical change in UPDRS compared to baseline | Unified Parkinson's Disease rating scale (UPDRS total score ranges between 0 - normal - to 199 points - severe) | through study completion, an average of 8 weeks | 
| Clinical change in H&Y compared to baseline | Hoehn and Yahr scale is a system for describing progress of Parkinson's disease (range between 1 -less affect- to 5-more affect) | through study completion, an average of 8 weeks | 
| Clinical change in MoCA compared to baseline | The Montreal Cognitive Assessment (MoCA) is a widely used screening assessment for detecting cognitive impairment (ranges between 0-more affect- and 30-normal) | through study completion, an average of 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IMAO-B, Safinamide, Rasagiline