Multiple-dose, safety, pharmacokinetics, and pharmacodynamics of a new selective estrogen receptor modulator, ERA-923, in healthy postmenopausal women.
ERA-923 is a new selective estrogen receptor modulator under clinical investigation for use in tamoxifen refractory metastatic breast cancer. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-daily oral ERA-923 (10-200 mg) for 28 days in healthy postmenopausal females. ERA-923 was well tolerated, and adverse events were mild and reversible. No clinically significant changes in laboratory values were found with ERA-923 versus placebo. ERA-923 appeared to undergo extensive metabolism and enterohepatic recirculation. In addition, pharmacokinetic analysis showed that a high-fat breakfast increased the extent of absorption. ERA-923-dosed subjects had no uterine or ovarian changes when evaluated with transvaginal ultrasound and compared to placebo subjects. Overall, ERA-923 was safe and well tolerated in postmenopausal women dosed for 28 days.
Cotreau
Monette M
MM
Clinical Research and Development , Wyeth-Ayerst Research, Cambridge, Massachusetts, USA.
Stonis
Lucille
L
Dykstra
Kevin H
KH
Gandhi
Thimma
T
Gutierrez
Maria
M
Xu
Jing
J
Park
Young
Y
Burghart
Peter H
PH
Schwertschlag
Ullrich S
US
D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers; D001842:Bone and Bones / Q000378:metabolism; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005215:Fasting / Q000502:physiology; D005260:Female; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology; D017698:Postmenopause / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology
C439584:2-(4-hydroxyphenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl)-1H-indol-5-ol; D015415:Biomarkers; D007211:Indoles; D008055:Lipids; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators