Post hoc comparison of daily rates of nausea and vomiting with once- and twice-daily galantamine from a double-blind, placebo-controlled, parallel-group, 6-month study

Background: A once-daily extended-release galantamine (GAL-ER) formulation has been designed to improve tolerability compared with twice-daily immediate-release galantamine (GAL-IR). Objective: The aim of this study was to conduct a post hoc analysis of the clinical presentation of nausea and vomiting with GAL-ER compared with GAL-IR in subjects with mild to moderate Alzheimer's disease (AD). Methods: This is the report of a post hoc analysis of a large, randomized, double-blind, placebo-controlled, multicenter trial of GAL-ER with GAL-IR as the active control in subjects with mild to moderate AD. Galantamine dose was titrated every 4 weeks by increments of 8 mg/d to a daily dose of 16 or 24 mg, based on tolerability. Daily rates of nausea and vomiting were compared for the GAL-ER and GAL-IR groups. AUCs of the daily percentage of subjects reporting nausea/vomiting during dose titration were calculated. Antiemetic use for nausea/vomiting was compared between GAL-ER and GAL-IR groups. Results: Demographic characteristics were similar between the GAL-ER, GAL-IR, and placebo groups. Nausea was reported by 16.9% (54/319) of GAL-ER, 13.8% (45/326) of GAL-IR, and 5.0% (16/320) of placebo patients; vomiting was reported for 6.6% (21/319) of GAL-ER, 8.6% (28/326) of GAL-IR, and 2.2% (7/320) of placebo patients. The mean (SD) daily rate of nausea in the total population was 3.1% (13.43%) in the GAL-ER group and 5.2% (22.07%) in the GAL-IR group (P = NS); the mean (SD) daily rate of vomiting for the total population was 0.6% (4.14%) in the GAL-ER group and 1.6% (14.50%) in the GAL-IR group (P = NS). The mean (SD) daily rate of nausea or vomiting in the total population was 1.2 (8.46) and 0.4 (5.44) in the placebo group, respectively. For subjects reporting nausea, the mean (SD, SE) percentage of days with nausea was lower with GAL-ER than with GAL-IR (18.4% [28.22%, 5.31%] vs 38.0% [48.23%, 6.04%]; P = 0.014). AUC of the daily percentage of subjects reporting nausea/vomiting during dose titration was significantly higher in the GAL-IR group compared with the placebo group (320.9 vs 102.9; P = 0.01); there was no statistical difference between the GAL-ER group and placebo (171.1 vs 102.9; P = NS). Antiemetic use by subjects reporting nausea or vomiting was significantly lower in the GAL-ER group than the GAL-IR group (33.3% vs 53.4%; P 0.028). Conclusions: In these subjects with AD, the daily percentage of subjects reporting nausea and vomiting, and the percentage of days with vomiting among subjects reporting vomiting, did not significantly differ between the GAL-ER and GAL-IR groups. However, GAL-ER was associated with a significantly lower percentage of days with nausea than GAL-IR among subjects reporting nausea. AUC of the daily percentage of subjects with nausea or vomiting during dose titration did not differ significantly between the GAL-ER and placebo groups but was significantly higher in the GAL-IR group than placebo. Subjects with nausea or vomiting who received GAL-ER reported significantly less antiemetic use than those treated with GAL-IR. These results suggest the need for additional studies to explore the potential differences in the tolerability of these formulations.