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Randomized Controlled Trial
. 2013 Oct;19(10):745-52.
doi: 10.1111/cns.12158. Epub 2013 Aug 7.

A 24-week, randomized, controlled trial of rivastigmine patch 13.3 mg/24 h versus 4.6 mg/24 h in severe Alzheimer's dementia

Martin R Farlow  1 , George T Grossberg, Carl H Sadowsky, Xiangyi Meng, Monique Somogyi
Affiliations
Randomized Controlled Trial

A 24-week, randomized, controlled trial of rivastigmine patch 13.3 mg/24 h versus 4.6 mg/24 h in severe Alzheimer's dementia

Martin R Farlow et al. CNS Neurosci Ther. 2013 Oct.

Abstract

Aims: The 24-week, prospective, randomized, double-blind ACTION study investigated the efficacy, safety, and tolerability of 13.3 versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD).

Methods: Patients had probable AD and Mini-Mental State Examination scores ≥3-≤12. Primary outcome measures were as follows: Severe Impairment Battery (SIB) and AD Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV). Secondary outcomes were as follows: ADCS-Clinical Global Impression of Change (ADCS-CGIC), 12-item Neuropsychiatric Inventory (NPI-12), and safety/tolerability.

Results: Of 1014 patients screened, 716 were randomized to 13.3 mg/24 h (N = 356) or 4.6 mg/24 h (N = 360) patch. Baseline characteristics/demographics were comparable. Completion rates were as follows: 64.3% (N = 229) with 13.3 mg/24 h and 65.0% (N = 234) with 4.6 mg/24 h patch. The 13.3 mg/24 h patch was significantly superior to 4.6 mg/24 h patch on cognition (SIB) and function (ADCS-ADL-SIV) at Week 16 (P < 0.0001 and P = 0.049, respectively) and 24 (primary endpoint; P < 0.0001 and P = 0.025). Significant between-group differences (Week 24) were observed on the ADCS-CGIC (P = 0.0023), not NPI-12 (P = 0.1437). A similar proportion of the 13.3 mg/24 h and 4.6 mg/24 h patch groups reported adverse events (AEs; 74.6% and 73.3%, respectively) and serious AEs (14.9% and 13.6%).

Conclusions: The 13.3 mg/24 h patch demonstrated superior efficacy to 4.6 mg/24 h patch on SIB and ADCS-ADL-SIV, without marked increase in AEs, suggesting higher-dose patch has a favorable benefit-to-risk profile in severe AD.

Keywords: Clinical trial; Rivastigmine; Severe Alzheimer's disease; Transdermal patch.

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Conflict of interest statement

This article has not been previously published, nor is it under consideration for publication elsewhere.

Martin Farlow has served as a paid consultant for Accera, Alltech, Astellas, Avanir, Bayer, Biogen, Bristol‐Myers Squibb, Eisai Medical Research, GE Healthcare, Grifols, Helicon, INC Research, Medavante, Medivation Inc., Merck and Co. Inc., Novartis Pharma, Pfizer, Prana Biotech, QR Pharma, Sanofi Aventis Groupe, Schering‐Plough, Eli Lilly, Shire Pharmaceuticals, and Toyama; is a paid speaker for Eisai, Forest, Novartis, Eli Lilly and Pfizer; and receives research support from Accera, Biogen, Eisai, Eli Lilly and Co., Genentech, Navidea, Novartis Pharma, and Roche. George Grossberg has served as a consultant for Accera, Baxter Bioscience, Forest Labs, Lundbeck, Novartis, Otsuka, and Takeda; has received research support from Accera, Baxter, Elan, Forest, Janssen, NIH, Novartis, Noven, and Pfizer; and serves on a safety monitoring board for Merck. Carl Sadowsky has served on advisory boards for Novartis, Accera and Lilly, and speakers' bureau for Novartis, Accera, Lilly and Pamlab. Xiangyi Meng and Monique Somogyi are full‐time employees and stock holders of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Figures

Figure 1
Figure 1
Patient disposition throughout the study (randomized population). AEs, adverse events; N, number of patients in the population; n, number of patients with an assessment. One patient in each treatment group was randomized, but was not exposed to study medication.
Figure 2
Figure 2
Least‐squares means change from baseline to Week 24 on (A) SIB and (B) ADCS‐ADL‐SIV (modified full analysis set). ADCS‐ADL‐SIV, Alzheimer's Disease Cooperative Study–Activities of Daily Living scale–Severe Impairment Version; SEM, standard error of the least‐squares means; SIB, Severe Impairment Battery. Error bars represent the SEM. *P < 0.05; **P < 0.0001 versus 4.6 mg/24 h patch.
See this image and copyright information in PMC

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