A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer's disease--rivastigmine patch versus capsule.
OBJECTIVE
To compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD).


METHODS
In this 24-week, multicenter, double-blind, double-dummy, placebo- and active-controlled trial, patients with probable AD were randomized to one of four treatment groups: 12 mg/day rivastigmine capsules; 10 cm2 (9.5 mg/24 h) rivastigmine patch; 20 cm(2) (17.4 mg/24 h) rivastigmine patch; or placebo. Primary efficacy measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study--Clinical Global Impression of Change (ADCS-CGIC).


RESULTS
One thousand one hundred and ninety five AD patients from 21 countries participated in the study. Treatment differences (vs placebo) on the ADAS-Cog at Week 24 in 10 cm2 patch, 20 cm2 patch and capsule groups were 1.6 (p=0.005), 2.6 (p<0.001) and 1.6 (p=0.003). Treatment differences on the ADCS-CGIC were 0.3 (p=0.01), 0.2 (p=0.054) and 0.3 (p=0.009). Comparison between the 10 cm2 patch and the capsule revealed non-inferiority. Rates of nausea in the 10 cm2 patch and capsule groups were 7.2% and 23.1%, respectively; rates of vomiting were 6.2% and 17.0%, respectively. Moderate or severe skin irritation occurred in<or=10% patients across the four patch sizes (5, 10, 15 and 20 cm2).


CONCLUSIONS
The target dose of 10 cm2 rivastigmine patch provides efficacy similar to the highest doses of capsules with a superior tolerability profile. The transdermal patch with rivastigmine may offer convenience important to many caregivers and patients.
Winblad
Bengt
B
Karolinska Institutet Alzheimer Research Center, Stockholm, Sweden. Bengt.Winblad@ki.se
Cummings
Jeffrey
J
Andreasen
Niels
N
Grossberg
George
G
Onofrj
Marco
M
Sadowsky
Carl
C
Zechner
Stefanie
S
Nagel
Jennifer
J
Lane
Roger
R
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy*; D002214:Capsules; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates / Q000008:administration & dosage*; D000068836:Rivastigmine; D016896:Treatment Outcome
D002214:Capsules; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000068836:Rivastigmine