APPENDIX TABLE 1.
EFFECTS OF TREATMENT ON 24-H MEAN GH AND IGF-I AND GH SECRETORY DYNAMICS
| BASELINE | 6 MONTHS | 12 MONTHS | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arithmetic Mean (SD) * | minimum-maximum | Arithmetic Mean Change * | Ratio of Geometric Means [Fold change] † | 95% Cl | P Value MK-677 vs. Placebo ‡ | Arithmetic Mean Change * | Ratio of Geometric Means [Fold change] † | 95% Cl | P Value MK-677 vs. Placebo ‡ | |||
| GH and IGF-I | ||||||||||||
| 24-h Mean GH, μg/L | Placebo | 0.89 (0.58) | 0.16-2.28 | N=22 | -0.03 | 1.0 | 0.8-1.2 | -0.01 | 1.0 | 0.9-1.2 | ||
| MK-677 | 0.81 (0.53) | 0.09-2.33 | N=43 | 0.57 | 1.9 | 1.6-2.1 | <0.001 | 0.55 | 1.8 | 1.6-2.0 | <0.001 | |
| IGF-I, μg/L | Placebo | 112 (55) | 35-210 | N=22 | -3 | 1.0 | 0.9-1.1 | -4 | 1.0 | 0.9-1.1 | ||
| MK-677 | 87 (34) | 27-158 | N=43 | 50 | 1.6 | 1.4-1.7 | <0.001 | 45 | 1.5 | 1.4-1.6 | <0.001 | |
| GH Secretory Dynamics § | ||||||||||||
| # Secretion Events, pulses/24 h | Placebo | 18.5 (3.1) | 11-23 | N=22 | -0.4 | 1.0 | 0.9-1.1 | -1.2 | 0.9 | 0.9-1.0 | ||
| MK-677 | 18.5 (3.2) | 12-27 | N=43 | 0.9 | 1.1 | 1.0-1.1 | 0.189 | 1.3 | 1.1 | 1.0-1.1 | 0.003 ‖ | |
| Total 24-h Production Rate, μg/L/min | Placebo | 57.9 (35.4) | 5.7-122.7 | N=22 | 3.1 | 1.1 | 0.8-1.3 | -1.2 | 1.0 | 0.8-1.2 | ||
| MK-677 | 52.8 (33.5) | 6.9-137.2 | N=43 | 31.9 | 1.8 | 1.6-2.2 | <0.001 | 29.9 | 1.7 | 1.5-2.0 | <0.001 | |
| Total Pulsatile Production Rate, μg/L/min | Placebo | 51.8 (33.7) | 4.5-116.8 | N=22 | 2.9 | 1.1 | 0.8-1.4 | -1.4 | 1.1 | 0.8-1.4 | ||
| MK-677 | 47.3 (31.6) | 5.7-131.5 | N=43 | 27.9 | 1.8 | 1.5-2.2 | <0.001 | 26.7 | 1.7 | 1.5-2.0 | <0.001 | |
Baseline data presented are the arithmetic mean (SD) and the minimum and maximum values; mean changes (arithmetic differences) at 6 and 12 months are provided for reference.
GH data were transformed to the natural logarithmic scale before conducting the statistical analyses; results are reported as the ratio of geometric means (fold-changes from baseline) with upper and lower 95% confidence limits.
P values are for the pivotal comparison of the fold changes from baseline between the two groups at 6 and at 12 months.
Endogenous GH secretory dynamics were assessed using an automated multiple-parameter deconvolution method.
The increase in peak number was statistically significant with MK-677, however, the mean change from 18.5 to 19.7 (vs. 18.5 to 17.3 with placebo) is not considered biologically significant.
Abbreviations: GH = growth hormone; IGF-I = insulin-like growth factor I