Table 2.
Summary of Baseline and Baseline‐Adjusted IGF‐1 and IGFBP‐3 Pharmacodynamic Parameters in Japanese and Caucasian Subjects
| Treatment | ||||||||
|---|---|---|---|---|---|---|---|---|
| Population | Parameter (Unit)a | Placebo 0.5 mL | Placebob 1.0 mL | TV‐1106 7.5 mg | TV‐1106 15 mg | TV‐1106 50 mg | TV‐1106 100 mg | |
| IGF‐1 | Japanese | n | 8 | 4 | 8 | 8 | 7 | 8 |
| Baseline (ng/mL) | 176 (27) | 201 (27) | 175 (32) | 171 (53) | 163 (27) | 167 (47) | ||
| Emax (ng/mL) | 60 (28) | 50 (26) | 120 (32) | 147 (47) | 379 (94) | 427 (115) | ||
| TEmax (h) | 21.00 (2.00, 48.00) | 27.00 (6.00, 48.00) | 59.98 (36.00, 96.70) | 48.00 (30.00, 72.73) | 71.88 (30.00, 97.80) | 96.16 (70.63, 144.25) | ||
| AUEC0–t (ng·h/mL) | 2941 (5264) | 1401 (3091) | 11 990 (4897) | 16 278 (8786) | 41 074 (16 068) | 60 835 (14 188) | ||
| AUEC0–168 (ng·h/mL) | 1756 (3184) | 3 (4330) | 10 505 (2510) | 14 384 (6407) | 37 445 (12 000) | 47 522 (11 064) | ||
| Caucasian | n | 8 | 4 | 8 | 8 | 8 | 8 | |
| Baseline (ng/mL) | 186 (47) | 156 (43) | 185 (37) | 165 (49) | 188 (58) | 160 (43) | ||
| Emax (ng/mL) | 42 (22) | 63 (26) | 75 (31) | 135 (73) | 295 (75) | 412 (143) | ||
| TEmax (h) | 30.03 (8.00, 336.67) | 25.00 (0.00, 72.70) | 33.00 (18.00, 71.33) | 36.00 (4.00, 73.23) | 72.56 (48.00, 96.37) | 72.35 (48.00, 119.18) | ||
| AUEC0–t (ng·h/mL) | 1695 (1612) | 4331 (2216) | 6654 (5321) | 13 186 (8427) | 36 277 (12 917) | 53 398 (27 591) | ||
| AUEC0–168 (ng·h/mL) | 347 (1569) | 2815 (2179) | 4973 (3093) | 11 452 (7803) | 29 262 (8151) | 42 974 (16 771) | ||
| IGFBP‐3 | Japanese | n | 8 | 4 | 8 | 8 | 7 | 8 |
| Baseline (mg/L) | 4.46 (0.68) | 4.20 (0.62) | 4.70 (1.05) | 4.73 (0.77) | 4.34 (0.57) | 4.31 (0.38) | ||
| Emax (mg/L) | 0.68 (0.31) | 0.65 (0.55) | 0.90 (0.30) | 0.99 (0.54) | 1.76 (0.33) | 2.26 (0.58) | ||
| TEmax (h) | 24.00 (10.00, 336.67) | 14.00 (0.00, 144.97) | 72.04 (30.00, 167.22) | 59.17 (24.00, 144.43) | 95.20 (71.88, 120.25) | 108.87 (48.00, 167.33) | ||
| AUEC0–t (mg·h/L) | 39.67 (43.98) | 56.03 (86.80) | 89.19 (100.19) | 83.17 (83.33) | 237.57 (109.61) | 284.80 (136.16) | ||
| AUEC0–168 (mg·h/L) | –23.40 (67.90) | 3.75 (68.77) | 71.46 (54.88) | 67.45 (66.94) | 175.00 (46.63) | 219.38 (57.85) | ||
| Caucasian | n | 8 | 4 | 8 | 8 | 8 | 8 | |
| Baseline (mg/L) | 3.94 (0.62) | 4.55 (0.71) | 4.36 (1.13) | 4.24 (0.64) | 4.58 (1.13) | 3.81 (0.96) | ||
| Emax (mg/L) | 0.90 (0.69) | 0.33 (0.05) | 0.88 (0.41) | 1.04 (0.34) | 1.80 (0.85) | 2.11 (0.65) | ||
| TEmax (h) | 84.23 (24.00, 336.67) | 22.00 (4.00, 36.00) | 42.00 (10.00, 96.33) | 72.66 (8.13, 119.58) | 72.18 (2.00, 144.40) | 106.82 (72.25, 143.90) | ||
| AUEC0–t (mg·h/L) | 128.82 (186.89) | 2.35 (9.03) | 64.16 (72.33) | 99.96 (89.57) | 192.61 (169.75) | 328.69 (133.34) | ||
| AUEC0–168 (mg·h/L) | 60.50 (104.99) | –54.89 (39.03) | 33.21 (33.58) | 76.83 (58.68) | 136.83 (100.51) | 209.45 (86.24) | ||
Emax, maximum observed response; TEmax, time to achieve maximum observed response; AUEC0–t, area under the effect–time curve from time 0 to the time of the last quantifiable concentration; AUEC0–168, area under the effect–time curve from time 0 to 168 hours postdose.
a
Parameters are presented as mean (standard deviation) except for TEmax, which is median (minimum, maximum).
b
The 1.0‐mL placebo group was included to control for the high volume injected in the 100‐mg TV‐1106 dose group.