TABLE 3.
Study AC‐077‐101: Results of bioequivalence determination, pharmacokinetic analysis set
| Parameter | Geometric means ratio (treatment A/B; 90% CI) CVw % | |||||
|---|---|---|---|---|---|---|
| Group 1 | Group 2 | |||||
| FDC‐1 vs free combination | FDC‐2 vs free combination | |||||
| Macitentan (N = 57) | Tadalafil (N = 57) | ACT‐132577 (N = 56) | Macitentan (N = 58) | Tadalafil (N = 58) | ACT‐132577 (N = 56) | |
| Cmax, ng/mL | 1.0045 (0.9631, 1.0478) 13.50 | 0.7588 (0.7167, 0.8034) 18.38 | 0.9935 (0.9616, 1.0264) 10.32 | 1.1901 (1.1374, 1.2451) 14.64 | 0.9576 (0.9063, 1.0118) 17.86 | 1.0983 (1.0470, 1.1520) 15.15 |
| AUC0‐t, ng h/mL | 0.9815 (0.9527, 1.0113) 9.54 | 0.9151 (0.8687, 0.9639) 16.71 | 0.9826(0.9550, 1.0110) 9.03 | 1.1014 (1.0652, 1.1389) 10.80 | 0.9764 (0.9293, 1.0259) 16.01 | 1.0925 (1.0545, 1.1319) 11.20 |
| AUC0‐∞, ng h/mL | 0.9818 (0.9537, 1.0109) 9.31 | 0.9172 (0.8707, 0.9662) 16.70 | 0.9836(0.9572, 1.0107) 8.61 | 1.0981 (1.0641, 1.1332) 10.16 | 0.9765 (0.9293, 1.0260) 16.02 | 1.0884 (1.0502, 1.1281) 11.31 |
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‐1 in Group 1 and FDC‐2 in Group 2 (test).
Treatment B = free combination of macitentan and tadalafil (reference).