Table 8.
Statistical comparison of Cmax, AUC0–last, and AUC0–inf between treatment groups (pharmacokinetic parameters analysis set)
| Cmax (ng/mL) | AUC0–inf (h × ng/mL) | AUC0–last (h × ng/mL) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Analyte Treatment comparison |
n | Geometric LS mean ratioa | 90% CIa | Geometric LS mean ratioa | 90% CIa | Geometric LS mean ratioa | 90% CIa | ||
| Acetazolamide | |||||||||
| IHL-42X fasted versus RLD acetazolamide | 121 | 0.597 | (0.550, 0.647) | 118 | 0.910 | (0.865, 0.958) | 121 | 0.882 | (0.838, 0.929) |
| IHL-42X fasted versus IHL-42X fed | 117 | 0.807 | (0.744, 0.875) | 115 | 0.993 | (0.944, 1.045) | 117 | 0.966 | (0.918, 1.017) |
| THC | |||||||||
| IHL-42X fasted versus RLD Dronabinol | 114 | 0.829 | (0.705, 0.975) | 71 | 0.948 | (0.822, 1.093) | 114 | 0.877 | (0.762, 1.010) |
| IHL-42X fasted versus IHL-42X fed | 114 | 0.397 | (0.345, 0.456) | 82 | 0.262 | (0.231, 0.298) | 114 | 0.221 | (0.196, 0.250) |
| OH-THC | |||||||||
| IHL-42X fasted versus RLD Dronabinol | 120 | 0.905 | (0.801, 1.023) | 97 | 0.956 | (0.861, 1.061) | 120 | 0.919 | (0.825, 1.024) |
| IHL-42X fasted versus IHL-42X fed | 116 | 0.880 | (0.793, 0.977) | 105 | 0.550 | (0.502, 0.602) | 116 | 0.532 | (0.486, 0.584) |
| COOH-THC | |||||||||
| IHL-42X fasted versus RLD Dronabinol | 120 | 0.918 | (0.838, 1.006) | 29 | 0.779 | (0.615, 0.986) | 120 | 0.946 | (0.862, 1.039) |
| IHL-42X fasted versus IHL-42X fed | 115 | 1.235 | (1.143, 1.335) | 19 | 0.822 | (0.641, 1.054) | 115 | 0.850 | (0.785, 0.920) |
PK parameters are defined in Table 2. Bioequivalence was concluded if the 90% CIs around the ratio fell within 0.80 and 1.25
AUC0–last area under the drug concentration-time curve, from time zero to time of the last measurable concentration, AUC0–inf AUC from time zero extrapolated to infinity, Cmax, maximum plasma concentration, CI confidence interval, LS least square, SD standard deviation, RLD reference listed drug (taro acetazolamide and marinol)
aGeometric LS mean was obtained by exponentiating the LS mean of log-transformed PK parameters. Ratio and its 90% CI were obtained by exponentiating the LS means and CI of treatment difference