TABLE 2.
Study AC‐077‐101: Summary of pharmacokinetic parameters of macitentan, ACT‐132577 and tadalafil by treatment in group 1 (FDC‐1) and group 2 (FDC‐2), pharmacokinetic analysis set
| Geometric means (95% CI); tmax: Median (range) | ||||||
|---|---|---|---|---|---|---|
| Macitentan | Tadalafil | ACT‐132577 | ||||
| Parameter | Treatment A FDC | Treatment B free combination | Treatment A FDC | Treatment B free combination | Treatment A FDC | Treatment B free combination |
| Group 1 (FDC‐1) | ||||||
| N | 57 | 57 | 57 | 57 | 56 | 56 |
| Cmax, ng/mL | 168.73 (154.87, 183.83) | 167.93 (153.73, 183.44) | 384.56 (353.66, 418.17) | 506.45 (471.51, 543.98) | 157.67 (144.85, 171.63) | 158.77 (145.26, 173.54) |
| AUC0‐t, ng h/mL | 4324.13 (4032.28, 4637.11) | 4404.26 (4081.93, 4752.05) | 12 733.26 (11 440.52, 14 172.08) | 13 908.13 (12 522.48, 15 447.11) | 16 534.42 (15 297.50, 17 871.36) | 16 821.24 (15 485.60, 18 272.09) |
| AUC0‐∞, ng h/mL | 4429.18 (4134.83, 4744.48) | 4509.81 (4187.36, 4857.09) | 12 825.31 (11 523.07, 14 274.71) | 13 975.28 (12 583.17, 15 521.40) | 17 799.76 (16 458.30, 19 250.56) | 18 090.62 (16 670.17, 19 632.11) |
| tmax, h | 9.00 (5.0–10.1) | 9.00 (4.0–10.1) | 4.00 (1.0–24.0) | 3.00 (1.0–5.0) | 48.00 (24.0–72.0) | 48.00 (24.0–72.0) |
| t1/2, h | 13.821 (13.037, 14.652) | 13.957 (13.209, 14.747) | 18.372 (16.637, 20.287) | 18.066 (16.472, 19.815) | 49.112 46.979, 51.343) | 48.526 (46.023, 51.166) |
| Group 2 (FDC‐2) | ||||||
| N | 58 | 58 | 58 | 58 | 56 | 56 |
| Cmax, ng/mL | 193.66 (181.52, 206.60) | 163.02 (151.29, 175.66) | 468.72 (438.22, 501.33) | 489.94 (460.06, 521.76) | 164.53 (154.17, 175.58) | 149.71 (139.70, 160.45) |
| AUC0‐t, ng h/mL | 4740.06 (4415.13, 5088.91) | 4296.41 (3989.60, 4626.81) | 13 995.62 (12 750.92, 15 361.83) | 14 316.68 (13 118.08, 15 624.80) | 17 924.06 (16 799.59, 19 123.80) | 16 415.81 (15 281.60, 17 634.19) |
| AUC0‐∞, ng h/mL | 4833.20 (4506.52, 5183.55) | 4394.02 (4086.54, 4724.64) | 14 056.64 (12 807.84, 15 427.20) | 14 378.46 (13 175.79, 15 690.89) | 19 406.69 (18 127.98, 20 775.59) | 17 833.72 (16 556.31, 19 209.70) |
| tmax, h | 9.00 (3.0–10.1) | 9.00 (4.0–12.0) | 3.00 (1.0–7.0) | 3.00 (1.0–9.0) | 48.00 (24.0–72.0) | 48.00 (24.0–72.0) |
| t1/2, h | 13.794 (12.808, 14.857) | 14.410 (13.419, 15.474) | 18.141 (16.709, 19.695) | 18.503 (16.878, 20.283) | 50.478 (47.992, 53.093) | 50.332 (48.000, 52.778) |
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; FDC = fixed‐dose combination; N = maximum number of subjects with data; PK = pharmacokinetic; t1/2 = terminal half‐life; tmax = time to reach maximum plasma concentration.
Treatment A = FDC of macitentan and tadalafil (test).
Treatment B = free combination of macitentan and tadalafil (reference).
Only subjects who had a full set of PK parameters for both treatments were included in the analysis.