Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled Phase 3 study of postmenopausal women with osteoporosis.
BACKGROUND
We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis.


METHODS
Healthy postmenopausal osteoporotic women (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. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination.


RESULTS
Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups.


CONCLUSIONS
Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis.


BACKGROUND



BACKGROUND
NCT00205777; Trial registration date: September 16, 2005.
Christiansen
Claus
C
Center for Clinical and Basic Research, Ballerup, Denmark. cc@Nordicbioscience.com
Chesnut
Charles H
CH
Adachi
Jonathan D
JD
Brown
Jacques P
JP
Fernandes
César E
CE
Kung
Annie Wc
AW
Palacios
Santiago
S
Levine
Amy B
AB
Chines
Arkadi A
AA
Constantine
Ginger D
GD
D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D007211:Indoles; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; C447119:bazedoxifene