title: A double-blind, randomized, ascending, multiple-dose study of bazedoxifene in healthy postmenopausal women.
abstract: Bazedoxifene is a novel selective estrogen receptor modulator in clinical development for the prevention and treatment of postmenopausal osteoporosis. This phase 1, double-blind, randomized, placebo-controlled study (N = 107) of healthy postmenopausal women examined the pharmacokinetics and safety/tolerability profile of multiple doses of bazedoxifene (1, 2.5, 5, 10, 20, 40, and 80 mg) administered orally once daily for 30 days. Bazedoxifene demonstrated a half-life of 25 to 30 hours, reached steady state within 7 days, and exhibited linear pharmacokinetics over a dose range of 5-80 mg. Fibrinogen levels decreased with bazedoxifene doses of 5 mg and greater; these changes were significant for bazedoxifene 20, 40, and 80 mg (P ≤ .05 vs placebo), but were not dose dependent. Bazedoxifene was associated with increased levels of sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin (CBG); only increases in the levels of CBG appeared to be dose related. Bazedoxifene was safe and well tolerated within the tested dose range. Bazedoxifene showed no differences from placebo in adverse event reports, vital sign measurements, or electrocardiogram findings.
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: McKeand
authors.affiliation: No longer affiliated with Pfizer Inc, USA.|Teva Pharmaceuticals, North Wales, PA, USA.
authors.forename: Gayle P
authors.initials: GP
authors.lastname: Orczyk
authors.affiliation: No longer affiliated with Pfizer Inc, USA.|Shire Pharmaceuticals, Wayne, PA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Ermer
authors.affiliation: No longer affiliated with Pfizer Inc, USA.|Amgen Inc, Thousand Oaks, CA, USA.
authors.forename: Arkadi A
authors.initials: AA
authors.lastname: Chines
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016014:Linear Models; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
keywords: bazedoxifene; menopause; osteoporosis; pharmacokinetics; selective estrogen receptor modulator