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P4‐404: Donepezil therapy for patients with Alzheimer's disease: Treatment benefits in “nonresponders”
Author(s) -
Wilkinson David,
Schwam Elias,
Feldman Howard,
Waldemar Gunhild,
Jones Roy W.,
Xu Yikang,
Schindler Rachel
Publication year - 2008
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.2008.05.2475
Subject(s) - donepezil , placebo , medicine , cognitive decline , alzheimer's disease , mini–mental state examination , cognition , odds ratio , odds , disease , dementia , psychology , psychiatry , logistic regression , pathology , alternative medicine
29 days, as follows: 7 mg (days 1-3), 14 mg (days 4-9), 21 mg (days 10-15), and 28 mg (days 16-29). Safety and tolerability were assessed throughout the study, for each individual who received at least one dose of the drug. Blood samples were obtained on days 1, 27, 28, and 29, and analyzed for memantine using liquid chromatography coupled to tandem mass spectrometry (LC-MS/ MS). Results: There were no serious adverse events (AEs) or deaths. Four participants discontinued the study: one due to an AE (somnolence), one due to a protocol violation, and two withdrew consent. Treatment-emergent AEs (TEAEs) were all mild in severity and in most cases judged possibly related to study drug. The most common TEAEs were headache, somnolence, and dizziness. One subject had a reversible increase in aspartate and alanine aminotransferases after discontinuation of study drug. None had a potentially clinically significant (PCS) change in vital signs from screening to endpoint, or a PCS change during the treatment, relative to predose values. The absorption rate of memantine from the ER capsule was relatively slow, with a median Tmax of 12 hours. Mean Cmax and Cmin were 127.1 21.1 ng/mL and 102.5 16.5 ng/mL, respectively. Mean elimination half-life was 55.7 9.5 h and AUC 0was 2726 430 ng/mL. Conclusions: Memantine ER capsule administration was safe and well-tolerated. The relatively small difference between Cmax and Cmin suggests small fluctuations in plasma levels during the steadystate dosing interval.