Apomorphine Pump in Early Stage of Parkinson’s Disease

INTERVENTION: Trade Name: APOKINON Product Name: APOKINON Pharmaceutical Form: Solution for infusion CONDITION: Parkinson’s disease ; MedDRA version: 19.1 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: The primary objective of the trial is to investigate the impact on the QoL of the apomorphine pump (APO group) compared to conventional optimized oral therapy (Control group) in earlier stages of PD, when motor complications have just developed Primary end point(s): The primary endpoint of the study is the difference in the PDQ39 summary index between the baseline assessment and the assessment at 12 months’ follow up. The two treatment groups (APO vs Control) will be compared. Secondary Objective: •To assess the impact on motor and non‐motor impairment of the APO group vs Control group;; •To assess the impact on personal, social and professional functioning for the APO group vs Control group;; •To investigate the safety and tolerability of the apomorphine pump vs conventional optimized oral therapy.; •To determine apomorphine pump‐related cost‐ effectiveness compared to conventional optimized oral treatment at 24 months from the French National Health Insurance perspective. ; Timepoint(s) of evaluation of this end point: 12 months' follow up SECONDARY OUTCOME: Secondary end point(s): 1‐ Patient Global Impression of Change (PGIC) ; 2‐ Neurologist Global Impression of change (CGI‐I) ; 3‐ Change in Non‐Motor Aspects of Experiences of Daily Living (MDS‐UPDRS I) ; 4‐ Change in Motor Aspects of Experiences of Daily Living in “on” and “off” medication (MDS‐UPDRS II) ; 5‐ Change in motor examination during “on” periods (MDS‐UPDRS III) ; 6‐ Change in motor complications with MDS‐UPDRS IV ; 7‐ Patient diaries: ; ? Change in the number of hours per day in the “best ON” state ; ? Change in the number of hours per day in ON with dyskinesia ; ? Change in the number of hours per day in OFF state ; ? Sleeping‐hours per day ; 8‐ Change in Score of the Non‐Motor Symptoms Scale for PD (NMSS) ; 9‐ Change in psychosocial functioning PD (SCOPA‐PS) ; 10‐ Changes in mood and occurrence and characteristics of depressive symptoms (BDI) ; 11‐ Change in occurrence of anxiety (STAI‐S) ; 12 ‐Change in Score of VAS ; 13‐ Change in cognitive function: Montreal Cognitive Assessment (MoCA); Free and cued selective reminding test (FCSRT), 10/36 Spatial Recall Test (SPART), Digit Symbol Modalities test (SDMT), Digit Span, Letter‐Number Sequencing Test (OTMT), Color Word Interference Test (CWIT), Benton judgement of line orientation test, Clock drawing test, Boston naming test short version, and semantic verbal fluency constituting the overall neuropsychological evaluation ; 14‐ Change in apathy (Apathy Scale and short version of LARS) ; 15‐ Change in medication (L‐DOPA equivalents) ; 16‐ The safety endpoints: ; ? Frequency and intensity of behavioral symptoms (Ardouin Scale) ; ? Frequency, type and severity of therapy‐related adverse events ; ? Skin changes ; ? Full blood count ; ? Epworth Sleepiness Scale ; 2 / 12 months' follow up ; 3 / 12 months' follow up ; 4 / 12 months' follow up ; 5 / 12 months' follow up ; 6 / 12 months' follow up ; 7 / 12 months' follow up ; 8 / 12 months' follow up ; 9 / 12 months' follow up ; 10 / 12 months' follow up ; 11 / 12 months' follow up ; 12 / 12 months' follow up ; 13 / 12 months' follow up ; 14 / 12 months' follow up ; 15 / 12 months' follow up ; 16/ 12 months' follow up ; 17‐ ‐ Incremental Cost‐Effectiveness Ratio (ICER) at 24 months following inclusion defined as (Average costs in “APO group” – average costs in “Control group”) / (average QALYs in “APO group”‐average QALYs in “Control group”) to determine the cost for one QALY gained in the “APO group” versus “Control group”. Timepoint(s) of evaluation of this end point: 1 / 12 months' follow up ; 17 / 24 months' follow up INCLUSION CRITERIA: ‐ Adults aged = 65 years, ‐ Idiopathic PD (According to British Brain Bank Criteria) without any other known or suspected cause of Parkinsonism, ‐ Hoehn and Yahr stage = 2.5 in the best ON, ‐ Disease duration = 4 years, ‐ Presence of fluctuations and/or dyskinesia for no more than 3 years, ‐ One of the two following forms of impairment: * Impairment in activities of daily living (MDS‐UPDRS II>6) due to PD‐symptoms despite medical treatment in the worst condition or * Impairment of social and occupational functioning (measured with SOFAS) due to PD‐symptoms despite medical treatment (51‐80%), ‐ PDQ39 completed, ‐ Able to understand and remember the components of the study, ‐ Written informed consent, ‐ Patients covered with social insurance. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age rang