Dementia associated with Parkinson disease
Conditions
Interventions
Patients will be randomized in a 1:1 ratio to either target Exelon® capsule 12
mg/day or target Exelon® 10 cm2 patch
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 (Code 294.1) (see Appendix 3), 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.
Exclusion criteria
Exclusion criteria: 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; 16. patients receiving antipsychotics who are not on stable doses of atypical antipsychotics for four weeks prior to baseline; 17. patients who have previously participated in any clinical study with anti-dementia drugs; 18. taken any of the following substances during the four weeks prior to randomization: * cholinesterase inhibitors or cholinergic drugs (e.g., rivastigmine, donepezil, tacrine, galantamine, succinylcho
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * 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 that are due, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary safety assessments: * Adverse events and Serious Adverse Events (SAEs) * Unified Parkinson*s Disease Rating Scale (UPDRS) Part III (motor subscale) * Forced Expiratory Volume in one second (FEV1) and Peak Expiratory Flow (PEF) * Schellong Test (orthostatic hypotension) * Epworth Sleepiness Scale (ESS) * Vital signs * 12-lead ECG * Concomitant CNS (Central Nervous System) medications Secondary efficacy assessments: * Mattis Dementia Rating Scale (MDRS) * Ten Point Clock Test (TPCT) * Neuropsychiatric Inventory (NPI-10) * Alzheimer*s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) * Modified Hoehn and Yahr Staging (UPDRS Part V) | — |
Countries
Netherlands
Outcome results
None listed