Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer’s Disease

Thomas N. Chase, Martin Farlow, Kathleen Clarence-Smith

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Available cholinergic drugs for treating Alzheimer’s disease (AD) provide modest symptomatic benefit. We hypothesized that co-administration of a peripheral anticholinergic to reduce dose-limiting adverse effects (AEs) would enable the safe/tolerable use of higher cholinesterase inhibitor doses and thus improve their antidementia efficacy. A modified single-blind, ascending-dose, phase IIa study of donepezil plus solifenacin (CPC-201) lasting 26 weeks was conducted in 41 patients with probable AD of moderate severity. Entry criteria included the use of donepezil at a dose of 10 mg/day during the preceding 3 months. The primary outcome measure was the maximum tolerated dose (MTD) of donepezil achieved (to protocol limit of 40 mg/day) when administered with the anticholinergic solifenacin 15 mg/day. Secondary measures included assessments of cognitive and global function, as well as of AEs. The mean ± SD donepezil MTD increased to 38 ± 0.74 mg/day (median 40 mg/day; p < 0.001); 88% of the study population safely attained this dose at the end of titration. Markedly reduced donepezil AE frequency, especially gastrointestinal, allowed this dose increase. There were no drug-related serious AEs or clinically significant laboratory abnormalities. At 26 weeks, Alzheimer’s Disease Assessment Scale Cognitive Component scores in the efficacy evaluable population improved by 0.35 ± 0.85 points over baseline (p < 0.05), an estimated 2.5 ± 0.84 points above 10 mg/day donepezil and 5.4 ± 0.84 points above historic placebo (both p < 0.05). Clinical Global Impression of Improvement scores improved by 0.94 ± 0.20 to 3.1 ± 0.20 points (p < 0.001). The findings suggest that limiting donepezil AEs by co-administration of solifenacin allows the safe administration of substantially higher cholinesterase inhibitors doses that may augment cognitive and global benefits in patients with AD.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalNeurotherapeutics
DOIs
StateAccepted/In press - Jan 30 2017

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Alzheimer Disease
Maximum Tolerated Dose
Cholinesterase Inhibitors
Cholinergic Antagonists
Therapeutics
Solifenacin Succinate
donepezil
Cognition
Cholinergic Agents
Population
Placebos
Outcome Assessment (Health Care)
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

Cite this

Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer’s Disease. / Chase, Thomas N.; Farlow, Martin; Clarence-Smith, Kathleen.

In: Neurotherapeutics, 30.01.2017, p. 1-12.

Research output: Contribution to journalArticle

Chase, Thomas N. ; Farlow, Martin ; Clarence-Smith, Kathleen. / Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer’s Disease. In: Neurotherapeutics. 2017 ; pp. 1-12.
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