The inter-assay coefficients of variation were described in a previous report . Samples were measured at each sampling time. Lumbar BMD was measured using DXA/QDR (Hologic, Bedford, MA, USA). Adverse events (AEs) were investigated by the physicians and classified using the system organ class from MedDRA version 12.0. Statistical analysis The concentrations
of teriparatide, calcium metabolism, and bone turnover markers are expressed as means±SE. In the 24 h Tideglusib cell line change analysis, calcium metabolism and bone turnover markers were compared to the 0 h value (paired t test). The bone turnover markers and lumbar BMD are expressed as the mean percent changes from corresponding week 0 values. The changes from FHPI mouse baseline were evaluated using paired t test. Ethical
considerations The protocol of the present study was approved by the Institutional Review Boards at each participating institution, and the study was conducted in compliance Selonsertib with the Declaration of Helsinki and Good Clinical Practice (GCP). Written, informed consent was obtained from all participants prior to their participation in the study. Results Subjects Twenty-eight subjects with osteoporosis were enrolled in this study. One subject was withdrawn from the study at the first week of injection at the subject’s request. The subjects’ baseline characteristics are shown in Table 1. The serum 25(OH)D level was only measured at 0 weeks. One subject with a vitamin D deficiency at baseline was not included. Table 1 Participants’ baseline characteristics Item Mean ± SD Age (years) 71.1 ± 3.6 Height (cm) 152.2 ± 5.9 Weight (kg) 49.2 ± 5.5 BMI (kg/m2) 21.4 ± 3.2 Lumbar BMD (g/cm2) Tryptophan synthase 0.668 ± 0.076 Corrected serum Ca (mg/dL) 9.7 ± 0.3 Serum P (mg/dL) 3.6 ± 0.5 Serum intact PTH (pg/mL) 37.2 ± 11.6 Serum 25(OH)D (ng/mL) 29.7 ± 7.5 Serum osteocalcin (ng/mL) 7.9 ± 3.3 Serum P1NP (ng/mL) 49.5 ± 23.3 Urinary DPD (pmol/μmol · Cr) 5.0 ± 2.2 Urinary NTX (nmol/mmol · Cr) 46.9 ± 21.5 Pharmacokinetics The 24 h changes in plasma teriparatide acetate concentrations were nearly equal
in each data collection week (Fig. 1). No major difference was found in peak concentrations at 30 min among 0, 4, 12, and 24 weeks. The distributions of mean values of PK parameters in each sampling week were as follows: C max 495.9–653.9 pg/mL, AUClast 53.0–70.5 ng · min/mL, AUCinf 55.5–74.1 ng · min/mL, T max 34.4–41.1 min, and T 1/2 57.4–123.4 min. Fig. 1 Mean change over 24 h of the plasma concentration of teriparatide acetate at 0 weeks (black circle), 4 weeks (white circle), 12 weeks (black triangle), and 24 weeks (white triangle). Data are plotted as means (±SE) Changes in calcium metabolism In each data collection week, the corrected serum Ca increased to a peak concentration (9.7–9.8 mg/dL) at 6 h and decreased to the baseline level at 12–24 h (Fig. 2a). During the 24 week dosage period, the serum corrected Ca level decreased significantly at 4 and 24 weeks (Fig. 2b).