In a study of 15 weeks duration, patients were randomized to receive single daily doses of placebo or either 5 mg/day or 10 mg/day of ARICEPT® for 12 weeks, followed by a 3-week placebo washout period. As in the 30-week study, to avoid acute cholinergic effects, the 10 mg/day treatment followed an initial 7-day treatment with 5 mg/day doses.

Effects on the ADAS-Cog: Figure 4 illustrates the time course of the change from baseline in ADAS-cog scores for all three dose groups over the 15 weeks of the study. After 12 weeks of treatment, the differences in mean ADAS-cog change scores for the ARICEPT® treated patients compared to the patients on placebo were 2.7 and 3.0 units each, for the 5 and 10 mg/day ARICEPT®treatment groups respectively. These differences were statistically significant. The effect size for the 10 mg/day group may appear to be slightly larger than that for 5 mg/day. However, the differences between active treatments were not statistically significant.

Figure 4. Time-course of the Change from Baseline in ADAS-cog Score for Patients Completing the 15-week Study.

Following 3 weeks of placebo washout, scores on the ADAS-cog for both the ARICEPT® treatment groups increased, indicating that discontinuation of ARICEPT® resulted in a loss of its treatment effect. The duration of this placebo washout period was not sufficient to characterize the rate of loss of the treatment effect, but, the 30-week study (see above) demonstrated that treatment effects associated with the use of ARICEPT® abate within 6 weeks of treatment discontinuation.

Figure 5 illustrates the cumulative percentages of patients from each of the three treatment groups who attained the measure of improvement in ADAS-cog score shown on the X axis. The same three change scores, (7-point and 4-point reductions from baseline or no change in score) as selected for the 30-week study have been used for this illustration. The percentages of patients achieving those results are shown in the inset table.

As observed in the 30-week study, the curves demonstrate that patients assigned to either placebo or to ARICEPT® have a wide range of responses, but that the ARICEPT® treated patients are more likely to show the greater improvements in cognitive performance.

Figure 5. Cumulative Percentages of Patients with Specified Changes form Baseline ADAS-cog Scores.The Precentages of Randomized Patients Within Each Treatment Group Who Completed the Study Were: Placebo 93%, 5mg/day 90% 10mg/day 82%.

Effects on the CIBIC plus: Figure 6 is a histogram of the frequency distribution of CIBIC plus scores attained by patients assigned to each of the three treatment groups who completed 12 weeks of treatment. The differences in mean scores for ARICEPT® treated patients compared to the patients on placebo at Week 12 were 0.36 and 0.38 units for the 5 mg/day and 10 mg/day treatment groups, respectively. These differences were statistically significant.

Figure 6. Frequency Distribution of CIBIC plus Scores at Week 12

In both studies, patient age, sex and race were not found to predict the clinical outcome of ARICEPT® treatment.

Severe Alzheimer's Disease

Swedish 24-Week Study

The effectiveness of ARICEPT® as a treatment for severe Alzheimer's Disease is demonstrated by the results of a randomized, double-blind, placebo-controlled clinical study conducted in Sweden (24-Week Study) in patients with probable or possible Alzheimer's Disease diagnosed by NINCDS-ADRDA and DSM-IV criteria, MMSE: range of 1-10. Two hundred and forty eight (248) patients with severe Alzheimer's disease were randomized to ARICEPT® or placebo. For patients randomized to ARICEPT®, treatment was initiated at 5 mg once daily for 28-days and then increased to 10 mg once daily. At the end of the 24-week treatment period, 90.5% of the ARICEPT® -treated patients were receiving the 10 mg dose. The mean age of patients was 84.9 years with a range of 59 to 99. Approximately 77 % of patients were women and 23 % were men. Almost all patients were Caucasian. Probable AD was diagnosed in the majority of the patients (83.6% of ARICEPT®-treated patients and 84.2% of placebo-treated patients).

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