Page 24 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

2.9; 24mg/day: OR 1.82; 95% CI 1.4-2.3; 32mg/day: OR 1.79; 95% CI 1.3-2.4), except for the 8mg/day
dose, which was not significantly different from placebo. Trials lasting 3 months demonstrated

statistically significant differences between galantamine and placebo on global rating scales for doses of
18mg/day (OR 2.44; 95% CI 1.2-5.0), 24mg/day (OR 2.11; 95% CI 1.0-4.6), and 36 mg/day (OR 2.7;
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95% CI 1.2-6.2). The good-rated trial not included in the systematic review provided consistent results.
The LOCF mean change in ADAS-cog from baseline to 26 weeks was -1.6 (± 0.36) for galantamine, -1.3
(± 0.31) for galantamine prolonged release capsule (PRC), and +1.2 (± 0.33) for placebo. Both

galantamine and galantamine PRC were numerically superior to placebo in CIBIC-plus scores, but
differences failed to reach statistical significance at 26 weeks.

Although most trials assessed behavior or functional status, the authors of the systematic review did not
pool these data, presumably because of differences in study design and reporting. Evidence from

individual trials is mixed. Two good-rated trials assessed activities of daily living with the ADCS-ADL
scale; ITT results statistically favored galantamine over placebo at 26 weeks in both trials. 49, 53 Another
trial that assessed activities of daily living using the PDS found no significant differences between
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galantamine and placebo. Three trials measured disability using the DAD scale; one reported
statistically significant differences between galantamine and placebo for doses of 24mg/day and
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32mg/day, one reported statistically significant differences for doses of 32mg/day but not for
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24mg/day, and one reported no differences for doses of 24mg/day or 32mg/day. One trial assessed
sleep quality using the NPI sleep score and the PSQ1; no differences were found between galantamine
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and placebo on either measure. Three trials assessed behavioral symptoms using the NPI; two reported
no statistically significant differences in NPI scores at 26 weeks 49, 51 and the other reported statistically
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significant differences at 22 weeks for doses of 16mg/day and 24mg/day.

Only one trial reported caregiver burden. 52, 64, 65 This study reported the caregiver distress component of
the NPI in a 22 week trial comparing galantamine 16mg/day and 24mg/day to placebo. At endpoint, only

the 24mg/day dose was significantly better than placebo (P = 0.05).

No galantamine trial specifically reported the effect of drug treatment on rates of institutionalization or
death.

Rivastigmine vs. placebo
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One good-rated systematic review, one fair-rated systematic review, and three placebo-controlled trials
were included in our review of rivastigmine. 55-57 The good-rated systematic review included 3 published

Alzheimer's Drugs Page 24 of 205