Table 3.
PD Response Summary of IGF-I to a Single Dose Administration of VRS-317 in the PK/PD Population (n = 48)
Dose | No. | Stability, ng/mL | Baseline, ng/mL | Cmax, ng/mL | Cmax (SDS) | Tmax, d | AUC0–t, ng·h/mL | Average, ng/mL |
---|---|---|---|---|---|---|---|---|
Placebo | 9 | 188 ± 49 | 106 ± 47 | ND | ND | ND | ND | 102 ± 49 |
0.05 mg/kg | 8 | 212 ± 41 | 97 ± 47 | 137 ± 58 | −1.1 ± 0.7 | 6.4 ± 6.5 | 2837 ± 1330 | 95 ± 44 |
0.10 mg/kg | 8 | 170 ± 30 | 57 ± 18 | 105 ± 43 | −1.2 ± 0.9 | 5.0 ± 2.9 | 2214 ± 855 | 74 ± 29 |
0.20 mg/kg | 8 | 214 ± 68 | 86 ± 30 | 196 ± 58 | −0.5 ± 0.9 | 4.1 ± 1.8 | 3541 ± 1260 | 118 ± 42 |
0.40 mg/kg | 8 | 165 ± 44 | 70 ± 40 | 248 ± 87 | 0.9 ± 1.4 | 4.5 ± 1.4 | 3771 ± 1524 | 126 ± 51 |
0.80 mg/kg | 7 | 197 ± 76 | 89 ± 31 | 280 ± 103 | 1.4 ± 1.3 | 5.1 ± 2.0 | 4884 ± 915 | 163 ± 31 |
Stability refers to the time during which daily rhGH treatment was given. Baseline refers to day 1, before the dose of VRS-317 or placebo. The IGF-I AUC was calculated using the linear trapezoid rule. Average IGF-I was calculated by dividing AUC by the observation interval of 29 days. The dose proportionality correlation coefficients (log:log) were 0.76 for baseline corrected Cmax and 0.76 for baseline corrected AUC0–t.
Abbreviations: AUC0–t, area under the curve from time zero to the last measurable time point; Cmax, maximum concentration; ND, not determined; Tmax, time to maximum concentration.