TABLE 4.
(a) Parameter estimates using the final dQTcF model and (b) mean predicted dQTcF (final dQTcF model) by occasion and dose
| (a) Parameter estimates – final dQTcF model | ||||
|---|---|---|---|---|
| Parameter | Estimate | Standard error | p value | 95% CI |
| DM | −0.22 | 0.05 | <0.0001 | −0.318 to −0.124 |
| INT | −4.00 | 1.03 | 0.0001095 | −6.02 to −1.98 |
| P145 | 0.25 | 0.02 | <0.0001 | 0.207–0.302 |
| P2 | 0.39 | 0.01 | <0.0001 | 0.37–0.419 |
| P3 | 0.33 | 0.02 | <0.0001 | 0.295–0.372 |
| IIV a | 7.84 | n/a | n/a | 6.54–9.42 |
| IOV a | 7.12 | n/a | n/a | 6.39–7.93 |
| RUV a | 9.18 | n/a | n/a | 8.92–9.45 |
| (b) Mean (90% CI) predicted dQTcF | |||
|---|---|---|---|
| Occasion | 60 mg (347 ng/ml) | 80 mg (380 ng/ml) | 100 mg (402 ng/ml) |
| W1D1–W1D3 predose | 1.76 (0.11–3.45) | 1.89 (0.236–3.6) | 1.98 (0.304–3.71) |
| W1D3–W2D1 predose | 10.6 (8.39–12.8) | 11.1 (8.82–13.4) | 11.4 (9.12–13.8) |
| W2D1–W3D1 predose | 5.74 (3.59–8.04) | 6.04 (3.82–8.41) | 6.23 (3.95–8.65) |
| W3D1–W4D1 predose | 1.76 (0.11–3.45) | 1.89 (0.236–3.6) | 1.98 (0.304–3.71) |
| W4 and above | 1.76 (0.11–3.45) | 1.89 (0.236–3.6) | 1.98 (0.304–3.71) |
Predictions (b) are presented as mean (90% CI) values for the mean maximum plasma concentration (in parentheses) across subjects at each dose level; doses represent q.d. dosing.
Random effects are expressed as standard deviations; standard errors and p values are not applicable.
Abbreviations: CI, confidence interval; D, day; DM, parameter describing the effect of the individual specific difference of baseline QTcF from population mean; dQTcF, QT interval prolongation corrected by Fridericia formula and by baseline; IIV, inter‐individual variability; INT, intercept; IOV, inter‐occasion variability; n/a, not applicable; P145, power estimate for occasions 1, 4, and 5; P2, power estimate for occasion 2; P3, power estimate for occasion 3; RUV, residual unexplained variability; W, Week.