A 25-week, open-label trial investigating rivastigmine transdermal patches with concomitant memantine in mild-to-moderate Alzheimer’s disease: a post hoc analysis

Abstract

Objective:

To investigate the tolerability and efficacy of the rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer’s disease receiving concomitant memantine.

Research design and methods:

Post hoc analysis of a 25-week, randomized, prospective, open-label, parallel-group study. Patients receiving donepezil were switched to rivastigmine patches (4.6 mg/24 h) immediately or following a 7-day withdrawal for 4 weeks (core phase), before titrating up to 9.5 mg/24 h for a further 20-week extension phase. Prior memantine therapy was continued throughout. Clinical trial registration: clinicaltrials.gov. NCT00428389.

Main outcome measures:

Tolerability (adverse events [AEs], serious AEs [SAEs] and discontinuations) and efficacy (cognition, global functioning and activities of daily living [ADLs]) were assessed for the rivastigmine transdermal patch, with or without concomitant memantine.

Results:

Overall, 135 and 126 patients received rivastigmine with and without memantine, respectively. Of these, 122 (90.4%) and 118 (93.7%) patients with and without memantine, respectively, completed the core phase; 120 and 114 patients, respectively, entered the extension phase, and 90 (75.0%) and 86 (75.4%) completed the study. The incidences of AEs (73.3 vs. 67.5%) and SAEs (10.4 vs. 7.1%) were both slightly larger in patients receiving concomitant memantine, but the differences were not statistically significant (95% CIs: −5.2, 16.9 and −3.6, 10.1 for AEs and SEAs, respectively). The incidence of gastrointestinal AEs was low in both groups. Discontinuation due to AEs was higher in patients who received memantine (17.0 vs. 11.9%). Changes in cognitive and global function were similar between groups. ADL scores worsened in both groups; significantly more in those treated with memantine.

Conclusion:

Use of the rivastigmine transdermal patch in patients on established memantine appears to be well-tolerated, with only modest, non-significant increases in AEs compared with monotherapy, and did not seem to affect cognition or global functioning adversely.

Keywords::

• Alzheimer’s disease
• Memantine
• Rivastigmine
• Switch
• Transdermal patch

Transparency

Declaration of funding

This post hoc analysis was carried out by Novartis Pharmaceuticals Corporation. Data for the analysis was collected from the US38 study (CENA713D US38) at multiple centers throughout the United States. The US38 study was sponsored by Novartis Pharmaceuticals Corporation. The sponsors were involved in the writing and reviewing of this manuscript.

Declaration of financial/other relationships

M.R.F has disclosed serving as a consultant for Abbott, Adamas, Accera, Adlyfe, AstraZeneca, Astellas, Bristol-Myers Squibb, CoMentis, Eisai, GlaxoSmithKline, Medivation, Merck, Neurochem, Novartis Pharmaceutical Corporation, Noven, OctaPharma, QR Pharm, Sanofi-Aventis, Sonexa, Takeda, Talecris and Toyama Pharm; receiving research grant support from Bristol-Myers Squibb, Elan, Eli Lilly, Pfizer, Novartis Pharmaceutical Corporation, OctaPharma and Sonexa, and serving as a speaker for Eisai, Forest, Janssen, Pfizer, Novartis Pharmaceutical Corporation. G.A. has disclosed serving as a speaker for Novartis Pharmaceuticals Corporation, Forest Pharmaceuticals, Bristol-Myers Squibb/Otsuka Pharmaceuticals, AstraZeneca, Wyeth Pharmaceuticals and Eli Lilly, and has disclosed receiving research support from Novartis Pharmaceuticals Corporation, Forest Pharmaceuticals, Janssen-Cilag, Pfizer, Myriad Genetics, Corcept Therapeutics, Elan, Wyeth Pharmaceuticals, Eli Lilly and AstraZeneca. Drs Olin and Meng are full-time employees and stockholders of Novartis Pharmaceuticals Corporation.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer1 has disclosed that he/she has acted as a consultant/advisor to Forest Pharmaceuticals and is on the Speakers’ Bureau for Forest Pharmaceuticals, Novartis and Accera. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgments

The authors would like to thank Diya Lahiri, PhD, at Medicus International for her editorial assistance and medical writing on the manuscript, which was financially supported by Novartis.