Table 3.
Summary pharmacokinetic parameters of roflumilast and roflumilast N-oxide from DERMIS-1 and DERMIS-2 (phase III studies 301 [NCT04211363] and 302 [NCT04211389])
| Analyte | Age group,years | N | BSA, % | Target dose,a mg | Week 4 conc., ng/mL | Week 4 extrapolated AUC24, h*ng/mL | Week 8 conc., ng/mL | Week 8 extrapolated AUC24, h*ng/mL |
|---|---|---|---|---|---|---|---|---|
| DERMIS-1 | ||||||||
| Roflumilast | 6–11 | 1 | 10 | 6.1 | NA | NA | 0.511 | 12.3 |
| 12–17 | 3 | 4.8 (1.3) | 4.6 (1.2) | 0.972 (0.226) | 23.3 (5.43) | 0.911 (0.500) | 21.9 (12.0) | |
| ≥ 18 | 241 | 6.0 (4.1) | 6.1 (4.2) | 2.05 (2.83) | 53.3 (69.1) | 1.78 (2.38) | 47.4 (58.3) | |
| N-oxide | 6–11 | 1 | 10 | 6.1 | NA | NA | 4.30 | 103 |
| 12–17 | 3 | 4.8 (1.3) | 4.6 (1.2) | 8.42 (3.80) | 202 (91.2) | 8.71 (5.49) | 209 (132) | |
| ≥ 18 | 241 | 6.0 (4.1) | 6.1 (4.2) | 11.8 (12.9) | 288 (310) | 9.86 (12.0) | 242 (290) | |
| DERMIS-2 | ||||||||
| Roflumilast | 6–11 | 1 | 8.0 | 8.2 | 2.36 | 56.6 | 2.19 | 52.6 |
| 12–17 | 5 | 8.3 (4.8) | 8.5 (4.9) | 0.331 (0.217) | 9.92 (3.13) | 0.857 (0.895) | 25.7 (21.0) | |
| ≥ 18 | 244 | 6.9 (4.8) | 7.1 (5.0) | 1.99 (2.22) | 50.6 (53.5) | 1.72 (2.13) | 43.7 (51.5) | |
| N-oxide | 6–11 | 1 | 8.0 | 8.2 | 24.0 | 576 | 25.6 | 614 |
| 12–17 | 5 | 8.3 (4.8) | 8.5 (4.9) | 3.53 (2.44) | 84.6 (58.4) | 6.72 (7.24) | 161 (174) | |
| ≥ 18 | 244 | 6.9 (4.8) | 7.1 (5.0) | 12.2 (14.1) | 294 (338) | 10.2 (12.8) | 249 (308) | |
Data are expressed as means (SD) unless indicated otherwise
API active pharmaceutical ingredient, AUC24 area under the concentration-time curve from 0 to 24 h, BSA body surface area, conc. concentration, NA sample not available, SD standard deviation
aTreated surface area was calculated as total BSA * treated BSA. To calculate a target dose applied, the estimated treated surface area (cm2) was multiplied by 2 (2 mg of cream/cm2) to get the estimated amount of cream applied, then multiplied by 0.003 (mg API/mg of cream) to get the target dose applied. To calculate the treated surface area, a theoretical total BSA of 17,100 cm2 was used for adults, while in adolescents (12–17 years of age), a theoretical total BSA of 15,800 cm2 was used, and for patients between 6 and 11 years of age, a theoretical total BSA of 10,100 cm2 was used