Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease.
LY450139 dihydrate, a gamma-secretase inhibitor, was studied in a randomized, controlled trial of 70 patients with Alzheimer disease. Subjects were given 30 mg for 1 week followed by 40 mg for 5 weeks. Treatment was well tolerated. Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta.
Siemers
E R
ER
Eli Lilly and Company, Indianapolis, IN 46085, USA. esiemers@lilly.com
Quinn
J F
JF
Kaye
J
J
Farlow
M R
MR
Porsteinsson
A
A
Tariot
P
P
Zoulnouni
P
P
Galvin
J E
JE
Holtzman
D M
DM
Knopman
D S
DS
Satterwhite
J
J
Gonzales
C
C
Dean
R A
RA
May
P C
PC
D000409:Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D001381:Azepines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010450:Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D010919:Placebos
D001381:Azepines; D004791:Enzyme Inhibitors; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; D010919:Placebos; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D000409:Alanine