The ACTION study: methodology of a trial to evaluate safety and efficacy of a higher dose rivastigmine transdermal patch in severe Alzheimer's disease.

Background: Two sizes of rivastigmine patch (5 cm(2) and 10 cm(2)) are currently approved in the US and Europe, while a 20 cm(2) rivastigmine patch has also been tested. A 15 cm(2) rivastigmine patch may provide an optimal balance between efficacy and safety. Earlier studies have demonstrated the efficacy of rivastigmine in severe Alzheimer's disease (AD), and supported the use of a higher dose patch in AD.

Objective: The ACTION (ACTivities of daily living and cognitION) trial (Study CENA713DUS44) is designed to evaluate the efficacy and safety of low-dose versus high-dose rivastigmine transdermal patch in patients with severe AD.

Methods: ACTION is a prospective, randomized, parallel-group, double-blind, multicenter study of patients (aged ≥50 years) with severe AD and a Mini-Mental State Examination score of 3-12. Novartis began recruitment in July 2009 and is conducting the trial in the United States. Patients are randomized to receive either a 5 cm(2) (4.5 mg/24 h) or a 15 cm(2) rivastigmine patch (13.3 mg/24 h) for 24 weeks. Patients receiving the 15 cm(2) patch will be up-titrated over 8 weeks, via 5 and 10 cm(2) patches. The primary efficacy outcomes include activities of daily living (ADLs), assessed with the Alzheimer's Disease Cooperative Study - Activities of Daily Living - Severe Impairment Version (ADCS-ADL-SIV), and cognition, assessed with the Severe Impairment Battery (SIB). Secondary outcomes include behavior (Neuropsychiatric Inventory), global functioning (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change), response rates, and safety.

Conclusions: The ACTION trial examines the efficacy and tolerability of a 15 cm(2) rivastigmine patch over a 24-week period in patients with severe AD. This is a novel trial in the development of rivastigmine, as it uses a design that does not include a placebo arm, is recruiting patients with severe AD, and includes an ADL measure as a co-primary efficacy variable. CLINICAL REGISTRATION NUMBER: CENA713D US44.