MOTION, Safinamide in Early IPD, as add-on to Dopamine Agonist

Exclusion Criteria

• •To be eligible for inclusion in this study the subjects must not meet any of the following criteria:
• •1. Any indication of forms of Parkinsonism, other than idiopathic Parkinson's Disease.
• •2. If female, be pregnant or lactating.
• •3. Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.
• •4. Currently experiencing end of dose wearing off or on-off phenomena, disabling peak dose or biphasic dyskinesias, or unpredictable or widely swinging fluctuations.
• •5. Current clinically significant gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease, including acute gastric ulcer, hypertension that is not well controlled, asthma, chronic obstructive pulmonary disease (COPD), and Type I diabetes. Subjects with a history of gastric ulcer who have not had a recent episode of acute gastritis and are not currently experiencing gastric pain will be eligible for inclusion.
• •6. Second- or third-degree atrioventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within 3 months of the screening visit, or significant ECG abnormality, including QTc ≥ 450 msec (males) or ≥ 470 msec (females), where QTc is based on Bazett's correction method.
• •7. Have received treatment with safinamide previously.
• •8. Concomitant disease likely to interfere with the study medication (e.g. capable of altering absorption, metabolism or elimination of the study drug).
• •9. History of, or current psychosis (e.g. schizophrenia or psychotic depression) or a score ≥ 3 on item 2 (thought disorder) or 3 (depression) of the UPDRS, Section I at screening.
• •10. Evidence of dementia or cognitive dysfunction, as indicated by a MMSE score \< 24 or a score ≥ 3 on item 1 (mentation) of the UPDRS, Section I at screening.
• •11. Depression, as indicated by a GRID-HAMD (17-item scale) score \> 17 at screening.
• •12. History of allergic response to anticonvulsants or anti-Parkinsonian agents.
• •13. Mental or physical condition (e.g., neurotic behaviour, crippling degenerative arthritis, or limb amputation), which would preclude performing efficacy or safety assessments.
• •14. Hypersensitivity or contraindications to MAO B inhibitors.
• •15. Current history of severe dizziness or fainting on standing, due to postural hypotension.
• •16. Neoplastic disorder, which is either currently active or has been in remission for less than one year.
• •17. Participation in a clinical trial within 30 days of entry into the trial (screening visit) or has received treatment with any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to screening.
• •18. Treatment of their Parkinsonian symptoms with a medication, other than a stable dose of a single dopamine agonist, during the 8 weeks preceding the screening visit.
• •19. Treatment with any agent known to significantly inhibit or induce drug-metabolising enzymes (e.g., barbiturates, phenothiazines, etc.) within 4 weeks preceding the screening visit.
• •20. Treatment with opioids (e.g., tramadol, meperidine derivatives), SNRIs (e.g., venlafaxine, duloxetine), tri- or tetra-cyclic antidepressants, MAO inhibitors (e.g. selegiline), in the 8 weeks prior to the screening visit. Dextromethorphan will be permitted if used for treating cough.
• •21. Treatment with a depot neuroleptic within one injection cycle, or oral neuroleptics within 4 weeks prior to the screening visit.
• •22. Treatment with a drug that has hepatotoxic potential, e.g., tamoxifen, within 4 weeks, or received radiation therapy or a drug with cytotoxic potential, e.g., chemotherapy, within one year prior to the screening visit.
• •23. Diagnosis of HIV, or tests positive for Hepatitis C antibodies, or Hepatitis B surface antigen.
• •24. Any abnormality that the investigator deems to be clinically relevant, either on medical history, physical examination, ECG or in a diagnostic laboratory test.
• •25. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy.
• •26. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.