The Effect of Amantadine as add-on Therapy for Motor Fluctuations in Advanced Parkinson's Disease: a Randomized Double-blinded Placebo-controlled Trial

Inclusion Criteria: Parkinson's disease diagnosis in agreement with the MDS criteria (Postuma et al., 2015) for at least 3 years HY 2-3 in Med ON condition Age: 30-80 years Signs of motor fluctuations for at least 4 weeks before screening, with a mean total awake time in the off state of at least 2 h, including morning akinesia despite anti-parkinsonian drug adjustment (best medical treatment)" Amantadine naïve (all other oral add-on treatments for motor fluctuations are allowed) Concomitant anti-Parkinson drug use should be stable for at least 4 weeks prior to screening Patients affiliated or beneficiary of a social security scheme. Patients who signed the written informed consent form. Patients in capacity to complete Hauser diaries Exclusion Criteria: Severe or unpredictable periods in the Off-state, or both; Clinically significant and unstable cardiovascular disease, psychiatric illness (including major depression, dementia, impulse control, disorders, and suicide ideation), or any other medical disorder that might have placed the patient at increased risk; Patient with behavioral disorder, ECMP item ≥ 3 Patients previously submitted to advanced treatments: subcutaneous continuous apomorphine infusion, deep brain stimulation and levodopa-carbidopa intestinal gel; Patients with cognitive impairment (Mini Mental Status Examination \< 26) Patients with a diagnosis of atypical parkinsonism (Progressive supranuclear Palsy, Multiple system atrophy, Lewy Body Dementia or Cort…