TABLE 5.
Study AC‐077‐103: Results of bioequivalence determination, pharmacokinetic analysis set
| Ratio of geometric means (treatment A/B; 90% CI) CVw % | |||
|---|---|---|---|
| FDC‐2 vs free combination | |||
| Parameter | Macitentan (N = 34) | Tadalafil (N = 34) | ACT‐132577 (N = 34) |
| Cmax, ng/mL | 1.0608 (1.0014, 1.1238) 14.10 | 0.9015 (0.8413, 0.9661) 16.96 | 1.0198 (0.9819, 1.0591) 9.24 |
| AUC0‐t, ng h/mL | 1.0038 (0.9677, 1.0413) 8.94 | 1.0040 (0.9584, 1.0517) 11.35 | 0.9970 (0.9651, 1.0300) 7.93 |
| AUC0‐∞, ng h/mL | 1.0015 (0.9675, 1.0367) 8.42 | 1.0047 (0.9591, 1.0525) 11.34 | 0.9936 (0.9619, 1.0264) 7.91 |
AUC = area under the plasma concentration–time curve; AUC0‐t = AUC from time 0 to time t of the last measured concentration above the lower limit of quantification; AUC0‐∞ = AUC from time 0 to infinity; CI = confidence interval; Cmax = maximum plasma concentration; CVw = intrasubject (within‐subject) coefficient of variation; FDC = fixed‐dose combination; N = maximum number of subjects with data.
Treatment A = FDC of macitentan and tadalafil (test).
Treatment B = free combination of macitentan and tadalafil (reference).