Safinamide for Multiple System Atrophy (MSA)
Condition: Multiple System Atrophy
MeSH terms: Multiple System Atrophy; Shy-Drager Syndrome; Atrophy
Intervention: Safinamide Methanesulfonate; Safinamide Methanesulfonate matching placebo
Intervention description: 100 mg (free base); 100 mg placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 49.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: MSA, safinamide

Summary:

      The study is a placebo controlled study, with two parallel arms, in which participants will
      be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo
      in a double blind manner. Study population is patients diagnosed, with possible or probable
      parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participant must be 30 to 80 years of age inclusive, at the time of signing the
             informed consent;

          2. Participants who are diagnosed (with MRI confirmation) with possible or probable
             parkinsonian variant of Multiple System Atrophy less than 2 years ago;

          3. Participants with an anticipated survival of at least 3 years in the opinion of the
             investigator;

          4. Female not pregnant, not breastfeeding, and at least one of the following conditions
             applies:

               -  Not a woman of childbearing potential OR

               -  A woman of childbearing potential who agrees to follow the contraceptive guidance
                  during the treatment period and for at least 30 days after the last dose of study
                  intervention;

          5. Capable of giving signed informed consent

        Exclusion Criteria:

          1. History of neurosurgical procedure, including stereotactic surgery;

          2. History of Deep Brain Stimulation (DBS);

          3. History of bipolar disorder, severe depression, schizophrenia or other psychotic
             disorder;

          4. 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;

          5. History of dementia (DSM-V criteria);

          6. 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;

          7. Active hepatitis B or C;

          8. History of human immunodeficiency virus (HIV) infection;

          9. Subjects not able to swallow oral medications;

         10. Subjects with severe orthostatic symptoms;

         11. Impaired ambulation, i.e. falling more than once per week, bedridden patients or
             confined to a wheelchair during the whole day;

         12. Subjects with active malignant neoplasms;

         13. Movement disorders other than MSA (e.g. Parkinson Disease, dementia with Lewy bodies,
             essential tremor, progressive supranuclear palsy, pharmacological or post-encephalic
             parkinsonism);

         14. Any clinically significant or unstable medical or surgical condition that, in the
             opinion of the investigator, might preclude safe completion of the study or might
             affect the results of the study;

         15. Not on a stable regime, for at least 4 weeks prior to the randomization (baseline
             visit), of

               1. oral levodopa (including controlled release, immediate release or a combination
                  of controlled release/immediate release), with or without benserazide/carbidopa,
                  with or without addition of a catechol O-methyltransferase (COMT) inhibitor or

               2. dopamine agonist, anticholinergic and/or amantadine.

         16. Patients should not have received treatment with monoamine oxidase inhibitors in the 2
             weeks prior to the randomization visit, nor treatment with levodopa infusion,
             pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 4 weeks prior to the
             randomization visit;

         17. Patients should not have received treatment with an oral or depot neuroleptic within
             12 weeks prior to the randomization visit;

         18. Use of any investigational drug within 30 days prior to screening or 5 half-lives,
             whichever is the longest;

         19. Montreal Cognitive Assessment (MoCA) ≤ 20;

         20. Laboratory assessments showing moderate or severe hepatic impairment (2x ULN);

         21. Allergy/sensitivity or contraindications to the investigational medicinal products
             (IMPs) or their excipients, anticonvulsants, levodopa or other anti-parkinsonian
             drugs;

         22. Any clinically significant condition which, in the opinion of the Investigator, would
             not be compatible with study participation or represent a risk for patients while in
             the study.