Effects of Galantamine in Alzheimers Disease: Double-blind Withdrawal Studies Evaluating Sustained Versus Interrupted Treatment

M.      Gaudig; U.      Richarz; J.      Han; B.      Van Baelen; B.      Schauble

Abstract

To evaluate the effects of galantamine withdrawal, and compare this with uninterrupted therapy, two 6-week double-blind withdrawal studies (Studies 1 and 2) were performed. These enrolled individuals who had completed one of two 3- or 5-month randomized clinical trials (parent trials) involving patients with mild to moderate Alzheimers disease (AD). In Study 1 (GAL-USA-11; n723), patients continuously treated with galantamine 16 mg/day exhibited a mean (± standard error [SE]) improvement in 11-item cognitive subscale of the Alzheimers Disease Assessment Scale score of 1.8 (± 0.46) points at Week 6 compared with the parent trial baseline, (p < 0.001 vs placebo; observed cases analysis). Over the same period, patients switched from galantamine to placebo and those who had received continuous placebo, exhibited mean (± SE) deteriorations of 0.7 (± 0.49) and 1.2 (± 0.49) points, respectively. Similar trends were apparent in Study 2 (GAL-USA-5; n=118). In Study 1, subgroup analyses demonstrated cognitive benefits with continuing galantamine treatment and deterioration associated with galantamine withdrawal in patients with advanced moderate AD (baseline Mini- Mental State Examination score ≤14) and in individuals deemed non-responsive in terms of Clinicians Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus) evaluation at the end of the parent trial (CIBIC-plus score > 4). No safety issues were identified. In patients with mild to moderate AD who have exhibited cognitive benefits from up to 5 months galantamine treatment, continuing therapy reinforces previously achieved benefit, whereas in patients in whom galantamine is discontinued, although no safety concerns arise, the natural progression of AD is apparent.

Keywords: Alzheimer's disease, clinical trial, dementia, galantamine, randomized withdrawal, treatment, galantamine discontinuation, ADAS-cog/11 score, CIBIC-plus evaluation