5 % and a one-sided type I error of 2.5 %. The primary efficacy variable was the percent change from baseline in lumbar spine BMD at week 52-Endpoint; the last valid post-baseline measurement was used when the week 52 value was missing (LOCF). Predefined secondary outcomes included changes in BMD at the lumbar spine and regions of the proximal femur, changes in biochemical markers of bone turnover, and incidence of morphometric vertebral fractures at week 104. No changes in secondary outcomes were made during the course of the study. Efficacy analyses were performed in the intent-to-treat (ITT) population consisting of all subjects who were randomized, received at least one dose of study drug, and had analyzable
BMD or bone marker data at baseline and at least one posttreatment time point. Ninety-five percent, two-sided confidence intervals (CIs) for the treatment difference were constructed and used to see more determine differences between IR daily and each of the DR weekly treatment groups. Nonparametric selleck methods were used to perform the statistical analysis of all bone biopsy parameters. The nonparametric Wilcoxon rank sum test was used for between-group comparisons. The nonparametric Hodges–Lehmann CIs (95 %) were constructed for the median differences between groups. Results Subjects A total of 1,859 women were screened; of these, 923 subjects were
randomized, and 922 subjects received at least one dose of study drug (Fig. 1). Baseline characteristics were previously described and were similar across treatment groups . The median daily dose of calcium was 1,000 mg for all three treatment groups, and the median daily dose of vitamin D was 800 IU for all three treatment groups. A similar percentage of subjects in each treatment group completed the 104-week study (IR daily group, 80.8 %; DR FB weekly group, 76.2 %; DR BB weekly group, 77.9 %). The most common reasons given for withdrawal, which AR-13324 manufacturer occurred at similar incidences across all three treatment groups, were adverse event and voluntary withdrawal. A high percentage of ITT subjects in all groups (96.7 % of
subjects in the IR daily group, 96.7 % 3-oxoacyl-(acyl-carrier-protein) reductase of subjects in the DR FB weekly group, and 95.1 % of subjects in the DR BB weekly group) took at least 80 % of the study tablets. Fig. 1 Disposition of subjects Efficacy assessments As reported previously, all three treatment groups experienced significant improvements from baseline in lumbar spine BMD after 1 year of treatment. The response to both the 35-mg DR groups at week 52 was shown to be non-inferior and not superior to that observed with the 5-mg IR tablet. All three treatment groups continued to show significant improvements from baseline in lumbar spine BMD during the second year of the study with both 35-mg DR groups showing significantly greater increases than the 5-mg IR group (Fig. 2). The least squares mean percent change from baseline in lumbar spine BMD at week 104 was 5.5 % (95 % CI, 5.0 to 6.