A 24-Week Efficacy, Safety and Tolerability of Rivastigmine Patch Study in Patients With Probable Alzheimer's Disease

The Alzheimer's Disease Assessment Scale (ADAS) is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. It was assessed by a mental health professional (e.g., M.D., Ph.D., Pharm.D., R.N., or other equivalent qualifications) with a minimum of 2 years research experience meeting certification requirements.

Time frame: Change at 24 weeks

Population: Per Protocol (PP): patients who received at least one dose of study drug, had a baseline assessment and at least one post-baseline assessment on treatment (after Day 140 and not more than 2 days after the last known date of study drug) of the primary efficacy variable and have no major protocol deviations.

Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is a caregiver-based Activities of Daily Living (ADL) scale composed of 23 items developed for use in dementia clinical studies. It was designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, as well as making judgments and decisions. Responses for each item were obtained from the caregiver through an interview. For each basic ADL, there was a forced choice of best response or a yes or no question with additional sub questions. Higher numbered scores and answers of yes reflected a more self-sufficient individual. Therefore, the higher total score, the higher functioning the patient was. The total score was the sum of all items and sub questions. The range for the total ADCS-ADL score was 0 to 78.

Time frame: Change at 24 weeks

Population: Per Protocol (PP): patients who received at least one dose of study drug, had a baseline assessment and at least one post-baseline assessment on treatment (after Day 140 and not more than 2 days after the last known date of study drug) of the primary efficacy variable and have no major protocol deviations.

Alzheimer's disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale provides a single global rating of change from baseline. It was recommended that the baseline interview be conducted by two raters, one designated as the primary rater, the other as a backup. Both raters were independent trained clinicians, experienced in the assessment of patients with dementia. Neither rater was involved in any other way with the patients' treatment or evaluation throughout the study. At baseline, both raters had access to all of the patient's available records and evaluations. Subsequently, for all ratings of change from baseline, the rater relied solely on information obtained during the baseline interview of the patient and caregiver, including written notes and, if available, the baseline interview audio- or videotape. The rater had no access to any other safety or efficacy data, including all previous post-baseline ADCS-CGIC ratings by either rater.

Time frame: Change at 24 weeks

Population: Per Protocol (PP): patients who received at least one dose of study drug, had a baseline assessment and at least one post-baseline assessment on treatment (after Day 140 and not more than 2 days after the last known date of study drug) of the primary efficacy variable and have no major protocol deviations.

The Mini-Mental State Examination (MMSE) was used to establish patient's eligibility for the study and it was also used as an efficacy parameter in the Double-blind Treatment Period. The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score of 30, with higher scores indicating betterfunction. The total MMSE score at screening was between 10 and 20, inclusive, in order forthe patient to be eligible to participate in the trial.

Time frame: Change at 24 weeks

Population: Per Protocol (PP): patients who received at least one dose of study drug, had a baseline assessment and at least one post-baseline assessment on treatment (after Day 140 and not more than 2 days after the last known date of study drug) of the primary efficacy variable and have no major protocol deviations.

NPI including Caregiver Distress Scale (NPI-D) assesses a wide range of behavior problems encountered in dementia patients to provide a means of distinguishing frequency and severity of changes in behavioral problems & facilitates rapid behavioral assessment using screening questions.10 behavioral problems & 2 neurovegetative domains were evaluated through an interview of the caregiver by a mental health professional. The scale includes both frequency & severity ratings of ea. domain as well as a composite domain score(frequency x severity). Frequency: 1(occasionally) - 4(very frequently)&severity:1(mild) - 3(marked).The sum of the composite scores of the 12 domains yields the NPI total score. The NPI-D: 0(not severe & not at all distressing) - 5 (very severe or extremely distressing) for each of the 12 domains. NPI-12 total score: from 0-144, the NPI-10 total score: from 0-120, & NPI-D score: from 0-60, all with higher scores indicating more severe behavioral disturbance.

Time frame: Change at 24 weeks

Population: Per Protocol (PP): patients who received at least one dose of study drug, had a baseline assessment and at least one post-baseline assessment on treatment (after Day 140 and not more than 2 days after the last known date of study drug) of the primary efficacy variable and have no major protocol deviations.