AMANTADINE HYDROCHLORIDE for Advanced Parkinson's disease

Inclusion criteria

• {"criterion_text":"- Parkinson’s disease diagnosis in agreement with the MDS criteria (Postuma et al., 2015) for at least 3 years\n- HY 2-3 in Med ON condition\n- Age: 30-80 years\n- 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)”\n- Amantadine naïve (all other oral add-on treatments for motor fluctuations are allowed)Patients who have taken Amantadine less than 7 days can be included if they did not stop Amantadine because of side effects or lack of efficacy.\n- Patients affiliated or beneficiary of a social security scheme\n- Patients who signed the written informed consent form.\n- Patients in capacity to complete Hauser diaries\n- Concomitant anti-Parkinson drug use should be stable for at least 4 weeks prior to screening"}

Exclusion criteria

• {"criterion_text":"- •\tSevere or unpredictable periods in the Off-state, or both\n- •\tPatients having any contraindication to amantadine treatment (see Summary of Product characteristic in the Appendix: known hypersensitivity to drugs of the amantadine class or any of the components, combination with anti-emetic neuroleptics, patient with a history of epilepsy, confusional state, hallucinations or severe psychoneurotic state not controlled by treatment, patient with a history of congestive heart failure or peripheral oedema, patients with history of mild eczema will be allowed to participate and closely monitored)\n- •\tA history of neuroleptic malignant syndrome or nontraumatic Rhabdomyolysis;\n- •\trenal failure and renal insufficiency (creatinine > 150 µmol/L)\n- •\tHas received any other investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening or plans to use an investigational drug (other than the study intervention) during the study\n- •\tstates of agitation or confusion\n- •\tdelirious syndromes or exogenous psychosis in the anamnesis\n- •\tPregnant female subjects or potential childbearing female participant without highly effective contraception\n- •\tClinically 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;\n- •\tPatient with behavioral disorder, ECMP item ≥ 3\n- •\tPatients with on-going advanced treatments: subcutaneous continuous apomorphine infusion, levodopa-carbidopa intestinal gel and foslevodopa/foscarbidopa subcutaneous pump;\n- •\tPatients with cognitive impairment (Mini Mental Status Examination < 26)\n- •\tPatients with a diagnosis of atypical parkinsonism (Progressive supranuclear Palsy, Multiple system atrophy, Lewy Body Dementia or Cortico-basal degeneration)\n- •\tPatients previously submitted to deep brain stimulation"}

Primary endpoints

• {"endpoint_text":"- The main evaluation criterion is the change from baseline to end-point (3 months) in motor fluctuation (Off-time) assessed by the Hauser diaries (average of 3 consecutive days).","definition_or_measurement_approach":"Change from baseline to 3 months in Off-time measured by Hauser diaries (average of 3 consecutive days)."}

Secondary endpoints

• {"endpoint_text":"- The change from baseline to end-point (3 months): a) Off-time responders rate ; b) The mean score of MDS-UPDRS part IV (Goetz et al., 2008b); c) The mean score of UDysRS part 2A (Goetz et al., 2008a) ; d) The mean score of New freezing of gait questionnaire (Nieuwboer et al., 2009); e) The mean score of Fatigue Severity Scale (Herlofson and Larsen, 2002; Krupp et al., 1989), MDS-UPDRS Part I-II-III (Goetz et al., 2007) f) The mean score of PDQ-39 (Jenkinson et al., 199","definition_or_measurement_approach":"Change from baseline to 3 months on listed clinical scales (Off-time responders rate; MDS-UPDRS part IV; UDysRS part 2A; New freezing of gait questionnaire; Fatigue Severity Scale; MDS-UPDRS Part I-II-III; PDQ-39)."}
• {"endpoint_text":"- The safety of amantadine, expressed as: the percentage of AEs, of severe AEs, of serious AE and of patients’ discontinuation due to AEs, all over the three months of treatment.","definition_or_measurement_approach":"Safety measured as percentage of adverse events, severe AEs, serious AEs and discontinuations due to AEs over 3 months."}
• {"endpoint_text":"- The change from baseline to week 15 in motor fluctuation (Off-time) assessed by the Hauser diaries comparing patients with GRIN2B polymorphism vs. without, patients with COMTHH vs. patients with COMTLL and in mutated GBA/LRRK2 carriers vs. no GBA/LRRK2 mutation carriers;","definition_or_measurement_approach":"Change from baseline to week 15 in Off-time by Hauser diaries, subgroup comparisons by GRIN2B, COMT genotype and GBA/LRRK2 mutation carrier status."}
• {"endpoint_text":"- The number of patients able to wear the PDMonitor during the first and the second week of assessment and the Short Assessment of Patient Satisfaction on PDMonitor in advanced PD patients;","definition_or_measurement_approach":"Feasibility endpoints: count of patients wearing PDMonitor in weeks 1 and 2 and patient satisfaction via Short Assessment of Patient Satisfaction on PDMonitor."}
• {"endpoint_text":"- the agreement in PD monitor outcomes changes from baseline to end-point (3 month) with clinical scales changes","definition_or_measurement_approach":"Agreement/ concordance analysis between PDMonitor outcome changes baseline-to-3 months and clinical scale changes."}

France

Earliest CTIS Part Ii Submission Date

17-06-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

585

Number Of Sites

18

Number Of Participants

132

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Toulouse

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France