Table 3.
Summary statistics as a percentage change from baseline of serum CTx at 24 and 168 h postdose following single doses of of ODN administered to healthy male and postmenopausal female subjects
| Treatment | Panel | CTx at 24 h | CTx at 168 h‡ | ||||
|---|---|---|---|---|---|---|---|
| n | Least-squares mean (95% CI) | Difference (95% CI) compared with placebo | n | Least-squares mean (95% CI) | Difference (95% CI) compared with placebo | ||
| Male | |||||||
| Placebo | A | 7† | −13.5 (−32.5, 11.0) | — | 4 | −3.7 (−30.5, 33.5) | — |
| Placebo | B | 8 | −4.4 (−24.6, 21.1) | — | 4 | 21.2 (−12.5, 67.9) | — |
| ODN 2 mg | A | 0 | ND | ND | 0 | ND | ND |
| ODN 5 mg | B | 6 | −55.8 (−66.0, −42.6) | −51.4 (−72.1, −31.8) | 6 | −2.6 (−26.8, 29.8) | −23.7 (−61.5, 13.3) |
| ODN 10 mg | A | 6 | −65.0 (−73.1, −54.4) | −51.5 (−70.6, −33.6) | 6 | −24.9 (−43.8, 0.4) | −21.2 (−50.9, 7.8) |
| ODN 25 mg | B | 6 | −72.8 (−79.1, −64.5) | −68.4 (−86.8, −51.3) | 6 | −44.7 (−58.6, −26.3) | −65.9 (−97.2, −36.6) |
| ODN 50 mg | A | 6 | −72.0 (−78.4, −63.5) | −58.5 (−76.3, −42.0) | 6 | −44.6 (−58.8, −25.5) | −41.0 (−68.4, −14.8) |
| ODN 100 mg | B | 6 | −61.7 (−70.8, −49.8) | −57.3 (−78.1, −37.9) | 0 | ND | ND |
| ODN 200 mg | A | 6 | −69.3 (−76.5, −60.0) | −55.9 (−73.8, −39.2) | 0 | ND | ND |
| ODN 400 mg | A | 6 | −72.2 (−78.6, −63.8) | −58.7 (−76.5, −42.2) | 0 | ND | ND |
| ODN 600 mg | B | 6 | −72.2 (−78.7, −63.8) | −67.8 (−86.4, −50.7) | 0 | ND | ND |
| ODN 25 mg (fed) | B | 0 | ND | ND | 0 | ND | ND |
| Placebo | C | 4 | −12.1 (−39.0, 26.6) | — | 2 | −16.3 (−51.0, 43.0) | — |
| ODN 50 mg | C | 6 | −78.0 (−84.1, −69.5) | −65.9 (−95.6, −40.2) | 6 | −69.6 (−77.6, −58.7) | −53.3 (−91.9, −19.8) |
| ODN 100 mg | C | 4*,† | −54.9 (−69.7, −32.8) | −42.7 (−79.8, −8.7) | ND | ND | ND |
Between-subject coefficient of variation ranged from 8 to 63% across panels/doses/time points; within-subject coefficient of variation ranged from 21 to 33% across panels/time points. There were no statistically significant differences between panel A and panel B placebo. Abbreviations are as follows: CI, confidence interval; CTx, C-terminal telopeptide of type I collagen; ND, CTx not measured at this dose level/time point; ODN, odanacatib; —, comparison not applicable. By design, CTx was not measured during the 2 and 25 mg fed treatment periods.
One subject with no reportable result.
One subject with values below the level of quantification at both baseline and 24 h; the percentage change could not be defined clearly.
CTx levels at 168 h were obtained as the predose measurement in the succeeding treatment period and thus are available only for 5, 10, 25 and 50 mg treatment periods; the number of available placebo observations is correspondingly reduced.