Mild to moderately severe dementia associated with Parkinson’s disease (PDD). MedDRA version: 9.1 Level: LLT Classification code 10012284 Term: Dementia due to Parkinson's disease
Conditions
Interventions
Trade Name: Exelon
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: rivastigmine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-
Trade Name: Exelon
Pha
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient will meet the following inclusion criteria at the time of the Screening Visit (Visit 1) and Baseline Visit (Visit 2), before being randomized to treatment : 1. 50-80 years of age (both inclusive); 2. males, and females not of child-bearing potential (surgically sterile or one year postmenopausal); 3. have a clinical diagnosis of idiopathic Parkinson’s disease according to the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria (see Appendix 2); 4. have a clinical diagnosis of Parkinson’s disease dementia according to DSM-IV criteria, with onset of symptoms of dementia at least 2 years after the first diagnosis of idiopathic Parkinson’s disease; 5. have a MMSE score of = 10 and = 24 (at Screening Visit only, Visit 1); 6. have sufficient education to have been able to read, write, and communicate effectively during the premorbid state; 7. be cooperative and willing to complete all aspects of the study, and capable of doing so, either alone or with the aid of a responsible caregiver, according to judgment of the investigator; 8. be residing with someone in the community throughout the study or, if living alone, in regular contact with the primary caregiver; 9. have a single caregiver, paid or unpaid, willing to accept responsibility for supervising the treatment, (e.g. application and removal of the patch daily at approximately the same time of day) and assessing the condition of the patient throughout the study, and for providing input to safety and efficacy assessments in accordance with all protocol requirements; 10. provide, if mentally competent (or if incompetent, their legally acceptable representative will provide) written informed consent prior to their participation in the study. Caregivers also will provide written informed consent. 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 range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Each patient with any of the following exclusion criteria at the Screening Visit (Visit 1) or the Baseline Visit (Visit 2) will not be entered into the study : 1. an advanced, severe, or unstable disease of any type that may interfere with the primary and secondary variable evaluations; 2. a score of 5 in the “on”-state on the Modified Hoehn and Yahr Staging (UPDRS Part V) assessment at screening; 3. a current diagnosis of any primary neurodegenerative disorder other than idiopathic PD e.g. Alzheimer’s disease, Frontotemporal dementia, Huntington’s disease, Dementia with Lewy bodies, Parkinson-Plus-Syndromes other than PDD (e.g. progressive supranuclear palsy or olivopontocerebellar degeneration); 4. a current diagnosis of any treatable dementia (hypothyroidism, syphilis, vitamin B12 or folate deficiency, hydrocephalus, chronic subdural hematoma) that is verified by the investigator to be the cause of dementia. Patients receiving stable therapy for hypothyroidism, vitamin B12 and folate deficiency, not considered to be the cause of dementia by the investigator, may be enrolled. Patients with abnormal laboratory diagnostic tests at screening not previously documented or further investigated are not eligible for enrollment; 5. a current diagnosis of probable vascular dementia according to the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria (NINDS-AIREN) criteria(see Appendix 4); 6. a current diagnosis of a major depressive episode according to DSM-IV criteria (Code 296) (see Appendix 5), or any other DSM-IV Axis I diagnosis that may interfere with the response of the patient to study medication, including bipolar disorder or schizophrenia, as assessed by psychiatric evaluation. Patients with major depression at baseline who are clinically stable under therapy may be enrolled; 7. a current diagnosis of active, uncontrolled seizure disorder; 8. a disability that may prevent the patient from completing all study requirements and, in particular, interfere with the assessment of dementia (e.g., blindness, deafness, severe extrapyramidal symptoms during the “on”-state); 9. a history of stereotaxic brain surgery for Parkinson’s disease (e.g. pallidotomy, deep brain stimulation, tissue transplant); 10. a current diagnosis or ECG, at screening or baseline, that displays evidence of bradycardia (<50 bpm), sick-sinus syndrome, conduction defects (sino-atrial block, second or third degree atrio-ventricular block); 11. a current diagnosis of acute, severe, or unstable asthmatic conditions; 12. a clinically significant urinary obstruction; 13. a current diagnosis of active, uncontrolled peptic ulceration or gastrointestinal bleeding within the last 3 months; 14. elevated liver function tests, specifically elevated alkaline phosphatase (AP), ALT (SGPT), AST (SGOT), or gamma-glutamyl-transferase (GGT) greater than 3 times the upper limit of the normal range; 15. a known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to Exelon® or to other cholinergic compounds; See other criteria page 19 of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety of Exelon® capsule (12 mg/day), over a period of 76 weeks, by assessing the worsening of the underlying motor symptoms of PD in patients with mild to moderately severe PDD. The primary objective will be assessed by measuring: • predefined adverse events (AEs) due, or potentially due, to worsening of PD motor symptoms (tremor, muscle rigidity, bradykinesia, fall). • study drug discontinuations due to predefined AEs, or potentially due, to worsening of PD motor symptoms (tremor, muscle rigidity, bradykinesia, fall). ;Secondary Objective: 1) To evaluate the long-term safety of Exelon® patch, over a period of 76 weeks, by assessing the worsening of the underlying motor symptoms of PD in patients with mild to moderately severe PDD. 2) To assess the overall long-term tolerability and safety (including the incidence of gastrointestinal adverse events, worsening of other PD motor symptoms, and peak expiratory flow) of Exelon® capsule and patch in patients with mild to moderately severe PDD. 3) To assess the effect of Exelon® capsule and patch on • patients with autonomic symptoms of PD at baseline • patients with sleep disorder at baseline • antipsychotic dose changes in patients with hallucinations at baseline Exploratory objectives : explore the impact of ApoE and BuChE genotype and inflammatory biomarkers on safety and efficacy outcomes. See other objectives in the protocol pages 14 and 15.;Primary end point(s): Analysis of the primary objective(s): - The two primary variables are: • the incidence rate of predefined AEs due to worsening of PD motor symptoms (tremor, muscle rigidity, bradykinesia, fall) in the Exelon® capsule group. • the discontinuation rate due, or potentially due, to predefined AEs due to worsening of PD motor symptoms (tremor, muscle rigidity, bradykinesia, fall) in the Exelon® capsule group. | — |
Countries
France, Italy, Spain
Outcome results
None listed