Cognitive effects of a prolonged-release formulation of galantamine (PRC) in patients with Alzheimer's disease – An open-label phase-IIIb-study

Background: Randomized controlled clinical trials have demonstrated the efficacy of galantamine-PRC in the treatment of Alzheimer's disease (AD)-patients. Objectives of this clinical trial were to further study the overall effect of galantamine-PRC on cognition and function in patients with AD.

Methods: Open-label, multi-center clinical trial (GAL-DEM-3002). Patients with mild to moderate AD (NINCDS-ADRDA criteria) received 16–24mg/day galantamine-PRC for 6 months. Primary objectives were to examine the effects on cognitive function using ADAS-cog and DemTect. Response-rate at endpoint was defined as percentage of patients with change in ADAS-cog ≤0. Statistical analyses based on intent-to-treat population (LOCF, t-test, Wilcoxon-test for dependent samples).

Results: 133 patients (48% with mild, 52% with moderate AD; mean age±SD 75.4±7.8 years; 68% women) were enrolled with 71% of the patients completing the study. 53% of the patients received 24mg/day galantamine-PRC. After 6 months mean total scores changed significantly, both in ADAS-cog, from 23.3±9.3 (baseline) to 20.4±9.7 (p<0.0001) and DemTect from 7.3±2.9 to 9.2±4.3 (p<0.0001). The response-rate was 64.2%. CGI demonstrated an improvement or stabilization for 83% of patients. 64% of the patients had at least one adverse event (AE). Most frequent AEs (>5%) were nausea, vomiting and headache. 28 patients discontinued due to AEs. 15 patients experienced a serious AE with 3 SAEs thereof considered as possibly related to study medication (syncope, hypotension, agitation). 2 deaths (sudden death, renal failure) were rated as unrelated to galantamine-PRC.

Conclusions: This clinical trial supports the evidence from placebo-controlled trials that galantamine-PRC is tolerated and effective in the treatment of AD-patients in a clinical setting.