Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial.
Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years.


BACKGROUND
We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis.


METHODS
In the core study, healthy postmenopausal women with osteoporosis (N=7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere.


RESULTS
A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium.


CONCLUSIONS
Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years.
de Villiers
T J
TJ
Panorama MediClinic and University of Stellenbosch, Room 118 Parow 7500, Cape Town, South Africa. Tobie@iafrica.com
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Palacios
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Lips
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Sawicki
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Levine
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Codreanu
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Kelepouris
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Brown
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D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009120:Muscle Cramp / Q000139:chemically induced; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced
D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene