Page 20 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

the two study drugs in dosing frequency, escalation schedules, and physical appearance. On average,
study participants were 73 years of age with a mean baseline MMSE score of 15. The primary study

endpoint was based on function assessed by the Bristol ADL; cognitive outcome measures included the
MMSE and ADAS-cog, behavioral disturbances were assessed with the NPI, and caregiver burden was
measured using the SCGB scale. At endpoint no statistically significant differences were observed in

functional abilities, cognitive symptoms, behavioral disturbances, or caregiver burden between the
donepezil and galantamine treatment groups. This trial was funded by the makers of galantamine.

One 12-week open-label trial compared flexible doses of donepezil 5-10mg/day (once daily) and
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galantamine 8-24mg/day (twice daily) in 120 patients with probable or possible AD; as in the 52-week
trial, only raters were blinded to treatment allocation. The mean age of study participants was 74 years
with a mean baseline MMSE score of 21. On average, baseline MMSE scores for patients in this trial

indicated less severe disease than in the 52-week trial. At baseline, patient demographics and disease
characteristics were similar in both groups. The primary outcome measure was unblinded physician and
caregiver satisfaction as measured on a scale specifically developed by the makers of donepezil for use in
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another head-to-head trial (presumably this instrument had not been previously validated). Secondary
outcome measures included cognition (ADAS-cog, MMSE) and disability (DAD). At 12 weeks, both
physician and caregiver satisfaction ratings were significantly better for donepezil (P < 0.001 and P <

0.01, respectively). Furthermore, donepezil-treated patients demonstrated significantly more
improvement on the ADAS-cog, MMSE, and DAD (P < 0.05). In contrast to the 52-week study that
demonstrated no difference between donepezil and galantamine, this trial was funded by the makers of

donepezil. Additionally, this trial demonstrated the worst reported galantamine response among all other
clinical studies. Both trials utilized similar dosing protocols.

Donepezil vs. Rivastigmine

One 12-week open-label trial compared flexible doses (5-10 mg/day) of donepezil to flexible doses (6-12
mg/day) of rivastigmine in 111 patients with mild to moderate AD.29 The mean age of study participants

was 74 years with a mean baseline MMSE score of 20; 54% of donepezil-treated patients and 64% of
rivastigmine-treated patients were female. With regard to baseline disease severity, patients in this trial

most closely resembled the 12-week trial comparing donepezil to galantamine. Cognitive symptoms and
disease severity were assessed with the ADAS-cog and MMSE, respectively. ADAS-cog raters were
blinded to treatment allocation, but unblinded clinicians administered the MMSE. At 12 weeks no

statistically significant differences in ADAS-cog or MMSE were reported for the two treatment groups.
These investigators also administered an unidentified measure of clinician and caregiver satisfaction.

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