Page 18 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

KEY QUESTION 1

How do donepezil, galantamine, rivastigmine, tacrine, and memantine or

combinations of these drugs (i.e., acetylcholinesterase inhibitor plus memantine)
compare in their efficacy or effectiveness for stabilizing symptoms and treating

behavioral disturbances in patients with Alzheimer’s Disease?

We included 26 RCTs and 8 systematic reviews/meta-analyses. Of the RCTs, 3 were head-to-head trials;
23 were placebo-controlled trials. Only one trial was deemed to be an effectiveness trial.

A. Description of studies

We did not identify any head-to-head, randomized, double-blind, parallel-group study. Of the three head-
to-head trials we identified, 27-29 all were open-label trials blinding only the rater to treatment allocation;
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two trials 27, 28 compared donepezil to galantamine and one trial compared donepezil to rivastigmine. We
included two systematic reviews 30, 31 that pooled placebo-controlled trials of donepezil, galantamine, and
rivastigmine to represent ChEIs as a class. Several other systematic reviews pooled placebo-controlled

trials for specific medications. 32-37

Of the included placebo-controlled trials, 11 compared donepezil to placebo, 32, 33, 38-48 6 compared

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galantamine to placebo, 49-54 3 compared rivastigmine to placebo, 55-57 1 compared tacrine to placebo, and
2 compared memantine to placebo. 59, 60 Most trials were 3 months to 1 year in duration; one trial
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followed patients for more than 3.5 years. Only one trial was deemed to be an effectiveness trial.
Doses generally were given within the range of the approved package labeling (see Table 1), although
several galantamine trials used doses above the recommended 24 mg/day and rivastigmine trials

commonly included a low dose arm of 1-4 mg/day.

B. Study populations

We included studies with a sample size greater than 100; the largest trial included in our review
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randomized 978 patients with probable AD. On average, the mean patient age was between 70 and 75
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years; one trial was conducted in a nursing home population with a mean age of 86 years. Most studies
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were conducted in patients with mild to moderate AD; one donepezil and two memantine trials 59, 60 were

Alzheimer's Drugs Page 18 of 205