PMID- 28138837
OWN - NLM
STAT- MEDLINE
DCOM- 20171218
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 14
IP  - 2
DP  - 2017 Apr
TI  - Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer's Disease.
PG  - 405-416
LID - 10.1007/s13311-016-0511-x [doi]
AB  - 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.
FAU - Chase, Thomas N
AU  - Chase TN
AD  - Chase Pharmaceuticals, Inc, 1825 K Street NW, Washington, DC, 20006, USA. 
      tchase@chasetherapeutics.com.
FAU - Farlow, Martin R
AU  - Farlow MR
AD  - Department of Neurology, Indiana University School of Medicine, 541 Clinical 
      Drive, CL299, Indianapolis, IN, 46202, USA.
FAU - Clarence-Smith, Kathleen
AU  - Clarence-Smith K
AD  - Chase Pharmaceuticals, Inc, 1825 K Street NW, Washington, DC, 20006, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Indans)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
RN  - KKA5DLD701 (Solifenacin Succinate)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*drug therapy
MH  - Cholinesterase Inhibitors/*therapeutic use
MH  - Donepezil
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Indans/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Muscarinic Antagonists/*therapeutic use
MH  - Piperidines/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Single-Blind Method
MH  - Solifenacin Succinate/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Treatment Outcome
PMC - PMC5398986
OTO - NOTNLM
OT  - Dementia
OT  - anticholinergic.
OT  - cholinesterase inhibitor
OT  - clinical trial
OT  - donepezil
OT  - solifenacin
EDAT- 2017/02/01 06:00
MHDA- 2017/12/19 06:00
PMCR- 2017/01/30
CRDT- 2017/02/01 06:00
PHST- 2017/02/01 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
PHST- 2017/02/01 06:00 [entrez]
PHST- 2017/01/30 00:00 [pmc-release]
AID - S1878-7479(23)01475-7 [pii]
AID - 511 [pii]
AID - 10.1007/s13311-016-0511-x [doi]
PST - ppublish
SO  - Neurotherapeutics. 2017 Apr;14(2):405-416. doi: 10.1007/s13311-016-0511-x.