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

Abstract

Background:

Two sizes of rivastigmine patch (5 cm² and 10 cm) are currently approved in the US and Europe, while a 20 cm rivastigmine patch has also been tested. A 15 cm 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 (4.5 mg/24 h) or a 15 cm rivastigmine patch (13.3 mg/24 h) for 24 weeks. Patients receiving the 15 cm patch will be up-titrated over 8 weeks, via 5 and 10 cm 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 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.

Key words::

• Activities of daily living
• Alzheimer's disease
• Cognition
• Dose
• response relationship
• Drug
• Rivastigmine
• Transdermal administration

Transparency

Declaration of funding

This study is being funded by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

M.R.F. has served as a consultant and speaker for Novartis Pharmaceuticals Corporation and has received honoraria and a research grants from Novartis Pharmaceuticals Corporation. G.G. has served as a consultant and has received honoraria from Novartis Pharmaceuticals Corporation. S.G. has been a member of the scientific advisory committee of Novartis Pharmaceuticals Corporation and has participated in symposia sponsored by Novartis Pharmaceuticals Corporation. X.M. is a full-time employee and stockholder of Novartis Pharmaceuticals Corporation. J.O. was a full-time employee and stockholder of Novartis Pharmaceuticals Corporation during the development of this study and manuscript. Peer reviewers may receive honoraria from CMRO for their review work. The peer reviewers have disclosed no relevant financial relationships.

Acknowledgments

The authors would like to thank Diya Lahiri, PhD, Medicus International, for her editorial assistance and medical writing on the manuscript. Medicus International activities pertaining to rivastigmine are funded by Novartis Pharmaceuticals Corporation.