Safety and Tolerability of Bazedoxifene/Conjugated Estrogens in Postmenopausal Women: Findings From a 1-Year, Randomized, Placebo- and Active-controlled, Phase 3 Trial
Dr. Sebastian Mirkin
United States of America
Disclosure : This study was sponsored by Wyeth Research, which was acquired by Pfizer Inc in October 2009.
18 slide(s) – English – 2012-03-28
Objective: To evaluate the endometrial safety and overall safety/tolerability profile of
bazedoxifene/conjugated estrogens (BZA/CE) in postmenopausal women over 1 year.
Design: The Selective estrogens, Menopause, And Response to Therapy (SMART)-5 trial
was a randomized, double-blind, placebo- and active-controlled, phase 3 study in
non-hysterectomized postmenopausal women. Subjects were randomized to BZA 20 mg/
CE 0.45 or 0.625 mg (n = 445 and n = 474, respectively), BZA 20 mg (n = 230), CE
0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg (n = 220), or placebo (n = 474).
Endometrial hyperplasia incidence was evaluated by endometrial biopsy. Adverse events
(AEs) were recorded and breast pain and bleeding were assessed using daily diaries.
Results: The endometrial hyperplasia rates were low (<1%) and similar for all groups after
1 year. The incidences of AEs, treatment-emergent AEs, and serious AEs were not different
among groups. The CE/MPA group showed higher rates of AE-related study discontinuations
than other groups (overall P = 0.012). The incidence of cardiac AEs was similar among
groups (range, 0%-0.4%). There was 1 venous thromboembolic event with CE/MPA and
1 cerebrovascular event with BZA 20 mg/CE 0.625 mg. The incidence of breast pain for both
BZA/CE doses was similar to that for placebo and significantly lower than that for CE/MPA
(P <0.01). BZA/CE showed high rates of cumulative amenorrhea and low rates of
bleeding/spotting similar to those for placebo and significantly better compared with
CE/MPA (P <0.001).
Conclusions: BZA/CE was associated with a favorable endometrial and overall safety
profile and showed improved tolerability compared with CE/MPA over 1 year in