Table 1 Design aspects of the successful trials
Design aspect | Single-API preparations Number of trials=440 | Fixed-Combination preparations = 72 dual-fixed and 9 triple-fixed combinations (n=167 APIs) |
|---|---|---|
BCS class (n [%]) | 436 | 167 |
BCS Class I | 104 (23.9) | 42 (25.2) |
BCS Class II | 220 (51.1) | 58 (34.7) |
BCS Class III | 59 (13.5) | 43 (25.7) |
BCS Class IV | 50 (11.5) | 24 (14.4) |
Dosage forms (n [%]) | ||
Oral dosage forms | 435 | 80 |
Immediate-release forms | 369 (84.8) | 72 (90.0) |
Modified-release forms | 66 (15.2) | 8 (10.0) |
All dosage forms | 438 | |
Tablets | 333 (76.0) | 72 (88.9) |
Capsules | 95 (21.7) | 4 (5.0) |
Liquid oral dosage forms | 7 (1.6) | 1 (1.2) |
Topical preparations | 2 (0.5) | 0 (0.0) |
Inhalers | 1 (0.2) | 1 (1.20) |
Drug toxicity index (n [%]) | 438 | 81 |
Wide therapeutic index | 432 (98.6) | 81 (100.0) |
Narrow therapeutic index | 6 (1.4) | 0 (0.0) |
Trial design | ||
2 x 2 crossover design | 383 (87.0) | 72 (88.9) |
Replicate design | 49 (11.0) | 9 (11.1) |
Parallel design | 9 (2.0) | |
Blinded design | ||
Yes | 14 (3.2) | 1 (1.2) |
No | 426 (96.8) | 80 (98.8) |
Washout period (days) (median [IQR a ]) | 0 to 60 (7 [7]) | 3 to 35 (14 [14]) |
Trial condition | ||
Fasting (n [%]) | 351 (79.8) | 61 (75.0) |
Fed (n [%]) | 89 (20.2) | 20 (25.0) |
Coefficient of variation (median [IQR]) | 5.1 to 123.3 (20.0 [12.2]) 432 | 6.0 to 47.9 (20.89 [12.8]) 80 |
Trials with CVw ≤30% (n [%]) | 350 (81.0) | 61 (76.3) |
Trials with CVw>30% (n [%]) | 82 (19.0) | 19 (23.7) |
Using wider equivalence margins | ||
2 x 2 crossover design | 2/383 | 0/72 |
Replicate design | 24/49 | 1/9 |
Health measurements of trial participants | ||
Minimum age (median [range]) | 19 (18 to 52) | 19 (18 to 24) |
Maximum age (median [range]) | 44 (18 to 87) | 45 (34 to 76) |
Body mass index (median [range]) | 23.8 (19.6 to 27.8) | 23.5 (18.5 to 25.5) |