| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10012271 |
| E.1.2 | Term | Dementia Alzheimer's type |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the efficacy of target Exelon 10 cm2 patch vs. target Exelon 15 cm2 patch in patients who have demonstrated cognitive decline in the initial Open-label Treatment Phase (Exelon 10 cm2 patch) with respect to the change from double-blind randomization baseline to Week 48 of the Double-blind Treatment Phase in cognition as assessed by the total ADASCog score. |
|
| E.2.2 | Secondary objectives of the trial |
| 1. To compare the efficacy of target Exelon 10 cm2 patch vs. target Exelon 15 cm2 patch in patients who have demonstrated cognitive decline in the initial Open-label Treatment Phase (Exelon 10 cm2 patch) with respect to: the change from double-blind randomization baseline over the 48-Week Double-blind Treatment Phase in instrumental activities of daily living as assessed by the ADCSADL instrumental activities subscale; the time to functional decline (i.e. interval between double-blind randomization baseline to first decline from double-blind randomization baseline) in instrumental activities of daily living as assessed by the ADCS-ADL instrumental activities subscale over the 48-Week Double-blind Treatment Phase; the change from double-blind randomization baseline to Week 48 of the Double-blind Treatment Phase in attention and executive function as assessed by the Trail Making Test Parts A and B; pls see protocol |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| Each patient will meet the following inclusion criteria at the time of the Baseline Visit (Visit 2): 1. 50-85 years of age; 2. males, and females not of child-bearing potential (surgically sterile or one year postmenopausal); 3. a diagnosis of dementia of the Alzheimer’s type according to the DSM-IV criteria; 4. a clinical diagnosis of probable AD according to NINCDS/ADRDA criteria. The brain scan (magnetic resonance imaging (MRI) or computed tomography (CT)) used for establishing that these criteria are met must have been done within two years prior to the baseline visit; 5. an MMSE score of ≥ 10 and ≤ 24; 6. sufficient education to have been able to read, write, and communicate effectively during the premorbid state; 7. cooperative, willing to complete all aspects of the study, and capable of doing so, either alone or with the aid of a responsible caregiver; 8. residing with someone in the community throughout the study or, if living alone, in regular contact with the primary caregiver; 9. a primary caregiver willing to accept responsibility for supervising the treatment, (e.g., application and removal of the patch daily at approximately the same time of day) assessing the condition of the patient throughout the study, and for providing input to efficacy assessments in accordance with all protocol requirements; 10. patients who reside in an assisted living facility may be allowed to participate in the study provided the patient will be assessed at the study site and that a caregiver who meets the requirements of the protocol has been identified for the patient. |
|
| E.4 | Principal exclusion criteria |
| Each patient will not meet any of the following exclusion criteria at the time of the Baseline Visit (Visit 2): 1. an advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk; 2. any medical or neurological condition other than AD that could explain the patient’s dementia (e.g., abnormal thyroid function tests, Vitamin B12 or folate deficiency, posttraumatic conditions, Huntington’s disease, Parkinson’s disease, syphilis); 3. a current diagnosis of probable or possible 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); 4. a current DSM-IV diagnosis of major depression, unless successfully treated with a stable dose of an antidepressant without anticholinergic properties for at least 4 weeks; 5. any other DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient’s response to study medication, including other primary neurodegenerative dementia, schizophrenia, or bipolar disorder; 6. a current diagnosis of active, uncontrolled seizure disorder; 7. a history within the past year or current diagnosis of cerebrovascular disease (e.g., stroke, transient ischemic attacks, aneurysms); 8. a current diagnosis of severe or unstable cardiovascular disease (e.g. unstable coronary artery disease, uncontrolled cardiac arrythmia); 9. a current diagnosis of bradycardia (< 50 bpm), sick-sinus syndrome, or conduction defects (sino-atrial block, second or third degree atrio-ventricular block); 10. a current diagnosis of acute, severe, or unstable asthmatic conditions [e.g., severe chronic obstructive pulmonary disease (COPD)]; 11. a current diagnosis of active, uncontrolled peptic ulceration or gastro-intestinal bleeding within the last 3 months; 12. clinically significant urinary obstruction; 13. history of malignancy of any organ system within the past 5 years unless patient is verified to be in stable condition with no active metastasis; 14. current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day; 15. history of allergy to topical products containing vitamin E; 16. a disability that may prevent the patient from completing all study requirements (e.g., blindness, deafness, severe language difficulty); 17. a known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine, or to other cholinergic compounds (e.g., pilocarpine, bethanechol, tacrine, donepezil, velnacrine, metrifonate, galantamine, or physostigmine); 18. taken any of the following substances prior to receiving study treatment: succinylcholine-type muscle relaxants during the previous 2 weeks; lithium during the previous 2 weeks; an investigational drug during the previous 4 weeks; a drug or treatment known to cause major organ system toxicity during the previous 4 weeks; any new psychotropic medication or dopaminergic agent or any psychotropic medication or dopaminergic agent not taken at a stable dose during the previous 4 weeks; rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase inhibitors (e.g., tacrine, physostigmine, or pyridostigmine), other approved treatments for Alzheimer’s disease during the previous 2 weeks with exception of stable treatment with memantine for at least 3 months before study entry (Visit 1); pls see protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this study is to compare the efficacy of target Exelon 10 cm2 patch vs. target Exelon 15 cm2 patch in patients who have demonstrated cognitive decline in the initial Open-label Treatment Phase (Exelon 10 cm2 patch) with respect to the change from doubleblind randomization baseline to Week 48 of the Double-blind Treatment Phase in cognition as assessed by the total ADAS-Cog score. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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