Table 3.
Effect of atrasentan on bone marker concentrations from baseline to week 9
| Marker† (log2- transformed) | Baseline, mean (SD) Placebo arm‡ Atrasentan arm‡ | Week 9, mean (SD) Placebo arm‡ Atrasentan arm‡ | Change from baseline | Estimate§ (P||) |
|---|---|---|---|---|
| BAP, u/L | 6.38 (1.52) 6.26 (1.49) |
5.58 (1.49) 5.62 (1.36) |
−0.80 −0.64 |
0.16 (.03) |
| CICP, ng/mL | 3.43 (1.10) 3.43 (1.08) |
2.97 (0.96) 2.82 (0.99) |
−0.45 −0.61 |
−0.16 (.02) |
| NTx, nM | 3.98 (1.15) 3.92 (1.13) |
3.83 (1.13) 3.83 (1.10) |
−0.15 −0.09 |
0.05 (.31) |
| PYD, nmol/L | 1.49 (0.63) 1.56 (0.69) |
1.17 (0.68) 1.10 (0.64) |
−0.31 −0.46 |
−0.15 (<.001) |
* BAP = bone alkaline phosphatase; CICP = C-terminal of type 1 collagen; NTx = N-telopeptides of type 1 collagen; PYD = pyridinoline; SD = standard deviation
† Increasing bone marker levels at week 9 were associated with a statistically significant increased risk of death: for BAP, the hazard ratio was 1.28 (95% confidence interval [CI] = 1.11 to 1.47; P < .001); for CICP, the hazard ratio was 1.35 (95% CI = 1.14 to 1.59; P < .001); for NTx, the hazard ratio was 1.36 (95% CI = 1.12 to 1.66; P = .002); and for PYD, the hazard ratio was 1.36 (95% CI = 1.12 to 1.66; P = .002).
‡ n = 311 in the placebo arm and n = 307 in the atrasentan arm for all markers at both baseline and week 9.
§ Estimates for the difference between arms (atrasentan – placebo) in the mean change in log2 bone marker concentrations (from baseline to week9), adjusted for bisphosphonate usage.
|| The threshold for statistical significance was ≤.0125 to control overall error rate across four tests at ≤.05. All tests were two-sided.