A 48-Week, Multicenter, Randomized, Double-Blind, Parallel-Group Evaluation of the Comparative Efficacy, Safety, and Tolerability of Exelon® 10 and 15 cm2 Patch in Patients with Alzheimer’s Disease Showing Cognitive Decline during an Initial Open-Label Treatment Phase.

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2007-000213-11-DE
• Date of registration: 12/10/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 48-Week, Multicenter, Randomized, Double-Blind, Parallel-Group Evaluation of the Comparative Efficacy, Safety, and Tolerability of Exelon® 10 and 15 cm2 Patch in Patients with Alzheimer’s Disease Showing Cognitive Decline during an Initial Open-Label Treatment Phase.
• Scientific title: A 48-Week, Multicenter, Randomized, Double-Blind, Parallel-Group Evaluation of the Comparative Efficacy, Safety, and Tolerability of Exelon® 10 and 15 cm2 Patch in Patients with Alzheimer’s Disease Showing Cognitive Decline during an Initial Open-Label Treatment Phase.
• Date of first enrolment: 20/12/2007
• Target sample size: 1200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000213-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

France, Germany, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients between 50 and 85 years of age with a diagnosis of dementia of the Alzheimer’s type according to the DSM IV criteria in addition to a clinical diagnosis of probable Alzheimer’s Disease (AD) according to the NINCDS/ADRDA criteria.
2. Patients with a baseline Mini-Mental State Examination (MMSE) score 10-24 inclusive.
3. Each patient will be required to have a primary caregiver willing to accept responsibility for supervising treatment, assessing the patient’s condition throughout the study, and for providing input into efficacy assessments.
4. Females not of child-bearing potential (surgically sterile or one year postmenopausal).

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:
1. Presence of an advanced, severe, progressive, or unstable disease of any type that could interfere with efficacy and safety assessments or put the patient at particular risk.
2. Any medical or neurological condition other than AD that could explain the patient’s dementia, a diagnosis of probable or possible vascular dementia.
3. A current DSM-IV diagnosis of unsuccessfully-treated major depression, or any other DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient’s response to study medication.
4. A current diagnosis of active, uncontrolled seizure disorder;
5. A history within the past year or current diagnosis of cerebrovascular disease (e.g., stroke, transient ischemic attacks, aneurysms);
6. A current diagnosis of severe or unstable cardiovascular disease (e.g. unstable coronary artery disease, uncontrolled cardiac arrythmia);
7. A current diagnosis of bradycardia (< 50 bpm), sick-sinus syndrome, or conduction defects (sino-atrial block, second or third degree atrio-ventricular block);
8. A current diagnosis of acute, severe, or unstable asthmatic conditions [e.g., severe chronic obstructive pulmonary disease (COPD)];
9. A current diagnosis of active, uncontrolled peptic ulceration or gastro-intestinal bleeding within the last 3 months;
10. Clinically significant urinary obstruction;
11. 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;
12. Current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day;
13. History of allergy to topical products containing vitamin E;
14. A disability that may prevent the patient from completing all study requirements (e.g., blindness, deafness, severe language difficulty);
15. 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);
16. Patients 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);
• centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants during the previous 4 weeks;
• selegiline unless taken at a stable dose during the previous 4 weeks;
• peripheral anticholinergics not taken at a stable dose during the previous 4 weeks.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer’s disease dementia

Intervention(s)

Trade Name: Exelon 4,6 mg/24 Stunden transdermales Pflaster
Product Name: Exelon Patch
Product Code: ENA713
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Rivastigmin
CAS Number: 123441-03-2
Current Sponsor code: ENA713
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 9-
Pharmaceutical form of the placebo: Transdermal patch
Route of administration of the placebo: Transdermal use

Trade Name: Exelon 9,5 mg/24 Stunden transdermales Pflaster
Product Name: Exelon Patch
Product Code: ENA713
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Rivastigmin
CAS Number: 123441-03-2
Current Sponsor code: ENA713
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-
Pharmaceutical form of the placebo: Transdermal patch
Route of administration of the placebo: Transdermal use

Product Name: Exelon Patch
Product Code: ENA713
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Rivastigmin
CAS Number: 123441-03-2
Current Sponsor code: ENA713
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 27-
Pharmaceutical form of the placebo: Transdermal patch
Route of administration of the placebo: Transdermal use

Trade Name: Exelon 4,6 mg/24 Stunden transdermales Pflaster
Product Name: Exelon Patch
Product Code: ENA713
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Rivastigmin
CAS Number: 123441-03-2
Current Sponsor code: ENA713
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 9-

Trade Name: Exelon 9,5 mg/24 Stunden transdermales Pflaster
Product Name: Exelon Patch
Product Code: ENA713
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Rivastigmin
CAS Number: 123441-03-2
Current Sponsor code: ENA713
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Main Objective: 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 ADAS-Cog score.

Primary end point(s): Primary efficacy parameter: Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Secondary efficacy assessment parameters:
• Alzheimer’s Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-Instrumental ADL)
• Trail Making Test Part A & B
• 10-item Neuropsychiatric Inventory (NPI-10).

Secondary Objective: • 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 and the time to decline over the 48-Week Double-blind Treatment Phase in instrumental activities of daily living as assessed by the ADCS-ADL instrumental activities subscale;
• To compare the safety and tolerability of target Exelon® 10 cm2 patch vs. target Exelon® 15 cm2 patch.

Secondary ID(s)

CENA713D2340

2007-000213-11-FR