Efficacy of RIVAstigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy (RIVA-PSP)

This is an interventional treatment trial for Progressive Supranuclear Palsy (PSP) Read More

Inclusion Criteria:

• Probable PSP of the Richardson subtype as defined by the NINDS-SPSP criteria modified so as to allow inclusions of patients who have first fallen within 3 years of disease onset.
• Aged 41 to 80 years at the time of screening
• Judged by site investigator to be able to comply with gait/balance and neuropsychological evaluations at baseline and throughout the study
• Able to ambulate independently or with assistance (cane)
• Score ≥ 20 on the mini-mental state examination (MMSE) at screening
• A reliable caregiver - defined as a person having frequent contact with subject (≥ 3 hours per day) and willing to fill the fall diaries and monitor study medication compliance and the subject's health and concomitant medication throughout the study - must accompany the subject to all visits.
• A fall or near fall rate ≥ 2/week in average (estimated through interview at screening and confirmed during a 2-week period between screening and baseline using fall postcards).
• Any parkinsonian medication taken by the subject must be stable in dose for 4 weeks prior to screening and must remain stable for the duration of the study
• Stable on all other chronic medications for 4 weeks prior to screening
• Written informed consent provided by subject and caregiver.

Exclusion Criteria:

• Non ambulatory patient.
• History and clinical examination suggesting another parkinsonian syndrome (Parkinson's disease, Dementia with Lewy Bodies, Corticobasal Degeneration, Multisystem Atrophy, Vascular Parkinsonism, tumoral parkinsonism, anti-psychotic drug-induced parkinsonism)
• Presence of other significant neurological or psychiatric disorders: Alzheimer's disease, epilepsy, history of stroke, psychotic disorder, severe bipolar or unipolar disorder
• A fall or near fall rate < 2/week in average (during a 2-week period between screening and baseline using fall postcards).
• Insufficient fluency in local language to complete neuropsychological, global and gait/balance assessments
• Score < 20 on the mini-mental state examination at screening
• Within 4 weeks of screening or during the course of the study concurrent treatment with any cholinesterase inhibitor medication (donepezil, galantamine, rivastigmine) or any cholinergic agent (agonist or antagonist) including memantine.
• History of deep brain stimulation surgery.
• Within 4 weeks of screening or during the course of the study concurrent treatment with beta blockers, any antipsychotic drugs or mood stabilisers.
• Any malignancy within 5 years of screening or current significant - judged as such by the site investigator - hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease.
• Presence of an active gastro-duodenal ulcer, unstable asthma or chronic obstructive pulmonary disease.
• History of or current urinary retention requiring either anticholinergic medication or urethral catheterisation.
• The systolic blood pressure measurement is > 190 or < 85 mm Hg and/or the diastolic blood pressure measurement is > 105 or < 50 mm Hg at screening.
• Clinically significant laboratory abnormalities at screening, including creatinine ≥ 2.5 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of the normal reference range.
• The ECG is abnormal at screening and judged to be clinically significant by the site investigator. Particular attention will be given to any sign suggesting conduction disorders.
• Treatment with any investigational drugs or device within 60 days of screening.
• Ongoing pregnancy or lactation. Women with childbearing potential not using any form of efficacious contraception.
• Any contraindication for rivastigmine as defined by the ANSM
• Known hypersensitivity to rivastigmine or any cholinesterase inhibitor medication.