Statistical analyses were performed using SAS Drug Development (SAS Institute). The safety analysis included all subjects
who received at least one dose of study medication in either treatment group. Results Patient disposition A total of 1,093 NU7441 chemical structure patients were screened; of these, 692 patients were randomized, and 690 patients received at least one dose of the study drug (Fig. 1). Baseline characteristics were similar in all three treatment groups (Table 1). A similar percentage of patients in each treatment group completed 12 months of the study (1 mg daily, 86.8%; 30 mg monthly, 91.3%; 50 mg monthly, 89.1%). The most common reason given for withdrawal was voluntary withdrawal: 19 PF-6463922 (61.3%) in the 1 mg daily group; 10 (50.0%) in the 30 mg monthly group; and 10 (40.0%) in the 50 mg monthly group. Fig. 1 Enrollment and outcomes. A total of 1,093 patients were screened, of which 692 were randomized to take minodronate at 30 mg monthly (229 subjects), 50 mg monthly (229 subjects), or 1 mg daily (234 subjects) Table 1 Demographics and baseline characteristics of subjects 1 mg daily (n = 234) 30 mg monthly (n = 229) 50 mg monthly (n = 229) Sex, n (%) Male 2 (0.9) 7 (3.1) 5 (2.2) Female
232 (99.1) 222 (96.9) 224 (97.8) Age (years) 67.8 [6.870] 68.6 [7.19] 67.3 [6.53] Body mass index (kg/m2) 21.88 [3.101] 21.87 [2.875] 22.03 [3.248] Menopause (years) 50.0 [4.20] 49.9 [3.81] 49.5 [4.57] Existing vertebral fractures, n (%) 60 (25.6) 61
(26.6) 72 (31.4) Lumbar BMD (g/cm2) Fludarabine ic50 0.6474 [0.06406] 0.6527 [0.06023] 0.6481 [0.06493] Lumbar BMD (T-score) −3.0551 [0.53830] −3.0112 [0.50616] −3.0494 [0.54561] Total hip BMD (g/cm2) 0.6684 [0.07949] 0.6644 [0.08213] 0.6685 [0.08765] Total hip BMD (T-score) −2.8791 [0.66802] −2.9129 [0.69021] −2.8784 [0.73656] Serum 25(OH)D (ng/mL) 27.0 [5.76] 26.9 [5.94] 25.8 [5.53] Serum BALP (U/L) 27.98 [9.165] 27.07 [8.687] 29.32 [14.321] Serum osteocalcin (BGP, ng/mL) 8.71 [2.756] 8.61 [2.543] 8.60 [2.205] Serum intact PTH (pg/mL) 42.2 [13.20] 43.7 [14.45] 44.1 [14.72] Serum Ca (mg/dL) 9.31 [0.343] 9.29 [0.321] 9.33 [0.335] Urine DPD (nmol/mmol) Liothyronine Sodium 6.47 [2.072] 6.54 [2.145] 6.38 [2.175] Urine NTX (nmol BCE/mmol Cr) 46.85 [21.527] 45.67 [19.720] 46.49 [20.692] Data are means [SD] for the indicated number of subjects in each group LS and hip BMD As shown in Fig. 2, both 30 and 50 mg monthly as well as 1 mg daily minodronate significantly increased LS-BMD from the baseline at all time points. Noninferiority of both monthly regimens to the daily regimen, with percent change in LS-BMD at 12 months as the end point, was determined.