Effects of Dopaminergic Therapy in Patients with Alzheimer's Disease: a 24 Weeks Prospective, Randomized, Double-blind, Placebo-controlled, Parallel Group, International, Multi-center Phase III Study Evaluating Efficacy and Safety of Rotigotine 4 Mg/24 Hrs in Combination with Rivastigmine 9.5 Mg/24 Hrs in Mild to Moderate Alzheimer's Disease Patients.
Overview
- Phase
- Phase 3
- Intervention
- Rotigotine 4Mg/24Hrs Patch
- Conditions
- Alzheimer Disease
- Sponsor
- I.R.C.C.S. Fondazione Santa Lucia
- Enrollment
- 348
- Locations
- 1
- Primary Endpoint
- Change from Baseline to Week 24 in the FAB to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo.
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a 24-week prospective, randomized, double-blind, placebo-controlled, multi-center phase III study evaluating efficacy and safety of rotigotine 4mg/24 hrs in combination with rivastigmine 9.5 mg/24 hrs in mild to moderate AD patients. The total study duration per patient from baseline to the end will be 24 weeks. The study has a placebo-controlled design to eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources.
Detailed Description
Patients will be screened at trial sites for determination of eligibility to enter the study on the basis of diagnostic evaluations, according to current diagnostic criteria for probable AD, and safety assessments (vital sign complete physical and neurological examinations). The efficacy assessments (cognitive/behavioral evaluations) will be performed at Baseline before starting treatment and repeated ontreatment at Weeks 6, 12 and 24. EEG neurophysiological examinations will be performed at Baseline and at Week 24. Plasma biomarkers will be collected at baseline and at Week 24. Visit windows are ±7 days for all the scheduled visits. At each in-clinic visit (or upon early termination), AEs will be recorded, at screening, baseline, weeks 6, 12 and 24 vital signs measured, and physical and neurological examination performed. During intervening times between visits, caregivers will be contacted by telephone at approximately at Weeks 4 and 16 and an unscheduled visit will take place if needed in response to a safety concern.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women (non-childbearing potential, as defined in Appendix 2) with a diagnosis of AD according to IWG criteria
- •Age 50-85 years
- •MRI or computerized tomography (CT) assessment, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3)
- •Patients who show CSF biomarker data supporting the diagnosis of AD (for Czech Republic only: lumbar punctures can be performed for screening purposes), or patients with a positive Amyloid Pet Scan will qualify for the study
- •Stable on a treatment with rivastigmine transdermal patch for at least 3 months, of which at least the last month was at 9.5mg/day, or for one month, if the patient had received donepezil before rivastigmine
- •Mild to moderate stage of AD according to MMSE ≥18 and ≤26
- •Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild)
- •Evidence of frontal lobe dysfunctions as assessed by FAB ≤14
- •Absence of major depressive disease according to GDS of \< 5
- •Formal education for five or more years
Exclusion Criteria
- •Failure to perform screening or baseline examinations
- •Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period
- •Clinical, laboratory or neuro-imaging findings consistent with:
- •other primary degenerative dementia (dementia with Lewy bodies, fronto- temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.);
- •other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.);
- •orthostatic hypotension and autonomic disorders
- •cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions \> one quarter of the total white matter);
- •other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.);
- •seizure disorder;
- •other infectious, metabolic, or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.).
Arms & Interventions
Rotigotine 4 mg
Rotigotine 4 mg/24 hours transdermal patch administration
Intervention: Rotigotine 4Mg/24Hrs Patch
Placebo
Placebo transdermal patch administration
Intervention: Placebo
Outcomes
Primary Outcomes
Change from Baseline to Week 24 in the FAB to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo.
Time Frame: From enrollment to the end of 24 weeks of treatment
FAB is a brief battery of six neuropsychological tasks designed to assess frontal lobe function
Secondary Outcomes
- Change from Baseline to Week 24 in the ADCS-ADL to evaluate efficacy of rotigotine in combination with rivastigmine on autonomies of daily living as compared to rivastigmine in combination with placebo(From enrollment to the end of 24 weeks of treatment)
- Change from Baseline to Week 24 in the MoCA to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo.(From enrollment to the end of 24 weeks of treatment)
- Change from Baseline to Week 24 in the CDR-SOB, to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo(From enrollment to the end of 24 weeks of treatment)
- Change from Baseline to Week 24 in the ADAS-Cog14 to evaluate efficacy of rotigotine in combination with rivastigmine on memory functions as compared to rivastigmine in combination with placebo.(From enrollment to the end of 24 weeks of treatment)
- Change from Baseline to Week 24 in the AMI to evaluate efficacy of rotigotine in combination with rivastigmine on levels of apathy and motivation as compared to rivastigmine in combination with placebo.(From enrollment to the end of 24 weeks of treatment)