IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease.
The rivastigmine patch is the first transdermal treatment for Alzheimer disease (AD). By providing continuous delivery of drug into the bloodstream over 24 hours, transdermal delivery may offer benefits superior to those of oral administration. This study compared the efficacy, safety and tolerability of rivastigmine patches with capsules and placebo. IDEAL (Investigation of transDermal Exelon in ALzheimer's disease) was a 24-week, double-blind, double-dummy, placebo- and active-controlled study. Patients with AD were randomized to placebo or one of three active treatment target dose groups: 10-cm(2) rivastigmine patch (delivering 9.5 mg/24 hours); 20-cm(2) rivastigmine patch (17.4 mg/24 hours); or 6-mg BID rivastigmine capsules. Primary efficacy measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. Secondary outcome measures assessed a range of domains, including behavior, cognitive performance, attention, executive functions, and activities of daily living. A total of 1,195 AD patients participated. All rivastigmine treatment groups showed significant improvement relative to placebo. The 10-cm(2) patch showed similar efficacy to capsules, with approximately two-thirds fewer reports of nausea (7.2% vs 23.1%) and vomiting (6.2% vs 17.0%), incidences statistically not significantly different from placebo (5.0% and 3.3% for nausea and vomiting, respectively). The 20-cm(2) patch showed earlier improvement and numerically superior cognitive scores vs the 10-cm(2) patch with similar tolerability to capsules. Local skin tolerability was good. The transdermal patch with rivastigmine may offer additional therapeutic benefits and may prove to be the best delivery system for this drug to treat AD.
Winblad
B
B
Karolinska Institutet Alzheimer Research Center, Stockholm, Sweden. Bengt.Winblad@ki.se
Grossberg
G
G
Frölich
L
L
Farlow
M
M
Zechner
S
S
Nagel
J
J
Lane
R
R
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D016503:Drug Delivery Systems / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007391:International Cooperation; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D000068836:Rivastigmine; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D010919:Placebos; D000068836:Rivastigmine