Table 4.
Summary statistics as a percentage change from baseline of urine NTx/Cr at 24 and 168 h postdose following single doses of of ODN administered to healthy male and postmenopausal female subjects
| Treatment | Panel | NTx/Cr at 24 h | NTx/Cr at 168 h¶ | ||||
|---|---|---|---|---|---|---|---|
| n | Least-squares (95% CI) | Difference (95% CI) compared with placebo | n | Least-squares mean (95% CI) | Difference (95% CI) compared with placebo | ||
| Male | |||||||
| Placebo | A | 8* | −4.8 (−32.0, 33.3) | — | 6 | 25.8 (−13.3, 82.4) | — |
| Placebo | B | 8 | 0.3 (−27.9, 39.6) | — | 6 | 17.8 (−18.7, 70.8) | — |
| ODN 2 mg | A | 6 | −15.6 (−41.9, 22.5) | −10.9 (−51.5, 29.3) | 6 | 11.7 (−23.2, 62.3) | −14.1 (−77.9, 48.7) |
| ODN 5 mg | B | 6 | −35.5 (−55.4, −6.6) | −35.8 (−72.5, −0.8) | 6 | 4.6 (−27.9, 51.7) | −13.2 (−73.1, 45.7) |
| ODN 10 mg | A | 6 | −65.2 (−76.0, −49.5) | −60.4 (−91.0, −32.8) | 6 | −35.1 (−55.2, −5.7) | −60.8 (−113.8, −12.1) |
| ODN 25 mg | B | 6 | −68.3 (−78.1, −54.0) | −68.6 (−98.9, −41.5) | 6 | −43.7 (−61.1, −18.3) | −61.5 (−110.1, −17.2) |
| ODN 50 mg | A | 6 | −78.8 (−85.4, −69.3) | −74.0 (−101.2, −50.3) | 6 | −62.1 (−74.0, −44.7) | −87.9 (−136.2, −46.1) |
| ODN 100 mg | B | 6 | −74.5 (−82.4, −62.9) | −74.8 (−104.5, −48.7) | 6 | −26.5 (−50.0, 7.9) | −44.4 (−98.3, 6.3) |
| ODN 200 mg | A | 6 | −82.2 (−87.8, −74.1) | −77.5 (−103.8, −54.7) | 0 | ND | ND |
| ODN 400 mg | A | 6 | −75.8 (−83.3, −64.9) | −71.0 (−99.5, −46.1) | 0 | ND | ND |
| ODN 600 mg | B | 6 | −73.9 (−82.0, −62.1) | −74.2 (−103.4, −48.5) | 0 | ND | ND |
| ODN 25 mg (fed) | B | 6 | −65.1 (−75.9, −49.5) | 3.1 (−12.2, 18.6)‡ | 0 | ND | ND |
| Female | |||||||
| Placebo | C | 3† | −13.0 (−49.5, 50.0) | — | 2 | −32.7 (−58.4, 8.9) | — |
| ODN 50 mg | C | 6 | −63.8 (−77.4, −41.9) | −50.8 (−101.4, −7.4) | 5§ | −78.4 (−84.1, −70.8) | −45.7 (−73.4, −21.8) |
| ODN 100 mg | C | 4§ | −70.4 (−83.4, −47.2) | −57.4 (−110.4, −13.9) | 0 | ND | ND |
Between-subject coefficient of variation ranged from 15 to 90% across panels/doses/time points; within-subject coefficient of variation ranged from 23 to 43% 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, NTx not measured at this dose level/time point; ODN, odanacatib; Urine NTx/Cr, urine N-terminal telopeptide of type I collagen normalized to creatinine; —, comparison not applicable.
Includes two subjects with one observation in each of two periods; replicate values were averaged prior to analysis.
One subject with no reportable result.
Comparison between ODN 25 mg fed and ODN 25 mg fasted.
Two subjects with values below the level of quantification at both baseline and 24 h; the percentage change could not be defined clearly.
NTx levels at 168 h were obtained as the predose measurement in the succeeding treatment period. Thus, not all dose levels have 168 h measurements; numbers of placebo observations are correspondingly reduced.