Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled Phase 3 study of postmenopausal women with osteoporosis

Claus Christiansen, Charles H Chesnut 3rd, Jonathan D Adachi, Jacques P Brown, César E Fernandes, Annie Wc Kung, Santiago Palacios, Amy B Levine, Arkadi A Chines, Ginger D Constantine, Claus Christiansen, Charles H Chesnut 3rd, Jonathan D Adachi, Jacques P Brown, César E Fernandes, Annie Wc Kung, Santiago Palacios, Amy B Levine, Arkadi A Chines, Ginger D Constantine

Abstract

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.

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

Trial registration number: NCT00205777; Trial registration date: September 16, 2005.

Figures

Figure 1
Figure 1
Subject disposition. The number of subjects who were screened, randomized and received at least 1 dose of study drug (safety population), and completed the study is shown. aDoes not include subjects (n = 92) who completed the 3-year core study and did not enter the extension study. bDefined as occurrence of new vertebral fracture or ≥7% decrease in BMD of the lumbar spine or hip at any time during the study (P < 0.01 among treatment groups, Chi-square test).

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Source: PubMed

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