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P1‐444: Assessing skin tolerability due to the change in the mode of administration of rivastigmine (oral to transdermal) according to two different strategies in Alzheimer patients
Author(s) -
Blesa Rafael,
Antúnez Carmen,
Boada Mercè,
Fernandez Manuel,
Gil Domènec,
Martinez Carlos,
Matías-Guiu Jordi,
Pascual Antonio Ortiz,
Peña-Casanova Jordi,
Robles Alfredo,
Sevilla Camino,
Viñuela Felix,
Barbanoj Manel
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.999
Subject(s) - tolerability , rivastigmine , transdermal , transdermal patch , adverse effect , medicine , titration , erythema , anesthesia , pharmacology , dementia , dermatology , chemistry , donepezil , disease , inorganic chemistry
day. It has not been generally assumed that a further dose increase will show such dose-response in more advanced AD patients due to greater loss of cholinergic neurons. To investigate whether a donepezil dosage >10 mg/day could confer additional benefit to patients with more advanced AD who were already on 10 mg/day, a once daily 23 mg extended-release donepezil HCl tablet with dose-proportional lower Cmax and delayed Tmax was developed. Methods: Patients with moderate-to-severe AD (MMSE 0-20) treated 3 months with donepezil immediate release 10 mg/day (10mg) were enrolled in a 24-week, double-blind, parallel-group trial comparing donepezil 23 mg/day extended-release tablets (23mg) with continued treatment with donepezil 10mg. Concomitant memantine was allowed. 1467 patients were randomized, 2:1, to 23mg and 10mg, respectively. Change from baseline (BL) in Severe Impairment Battery (SIB) score and scores at week 24 on the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) scale were co-primary efficacy assessments. Here, we report on post-hoc analyses of these endpoints based on disease severity by BL MMSE. Results: Among the full ITT population (n 1⁄4 1369), change from BL in SIB favored 23mg over 10mg: 2.6 versus 0.4, P 1⁄4 .0001. At week 24, CIBIC+ was 4.23 for 23mg versus 4.29 for 10mg, P 1⁄4 .1789. Treatment differences between 23mg and 10mg among patients selected to match the populations in published trials of memantine (MMSE 3-14 [n 1⁄4 732] and 5-14 [n1⁄4 680]) were: SIB 3.1 (P1⁄4 .0005) and 2.6 (P1⁄4 .0034), respectively; CIBIC+ 0.10 (P 1⁄4 .0508) and 0.11 (P 1⁄4 .0469), respectively. Patients comprising most of the more impaired end of the moderate-to-severe spectrum (eg, MMSE 0-16; 71% of ITT population) showed greater benefit with 23mg treatment than with continued 10mg treatment on both the SIB and the CIBIC+. The enhanced efficacy observed in patients with lower BL MMSE treated with 23mg was not associated with an increased AE rate versus the full 23mg group. Conclusions: More advanced AD patients (eg, MMSE 0-16) treated with donepezil 23 mg/day extended-release tablets demonstrated significant cognitive and global improvement relative to those treated with 10 mg/day.