Table 2.
Description of the 11 Phase 1 studies and one Phase 2 study analysed.
| Study description | Design | Subjects | *Samples | Doses/formulations |
|---|---|---|---|---|
| Single oral dose escalation | XO | 15 ♂HV | 32 | 0, 1–20 mg SOL |
| SOL-IR, young-elderly | XO | 20 ♂/7 ♀HV | 10 | 10 mg IR/SOL |
| I.v. dose escalation | XO | 8 ♂HV | 71 | 0, 0.6, 2, 6 mg i.v. |
| Multiple dose IR-CR | XO | 13 ♂HV | 65 | 7.5 mg IR TID, 20 mg CRS,CRM,CRF OD |
| Dose escalation IR-CR | XO | 26 ♂HV | 65 | 7.5, 15, 30 mg CR OD 2.5, 5, 10 mg IR TID |
| One tablet CR vs. 2 tablets CR | XO | 24 ♂HV | 30 | 45 mg, 15 + 30 mg CR |
| Relative F IR and CR | XO | 24 ♂HV | 59 | 4 mg i.v., 10 mg IR TID, 30 mg CR OD |
| Ketoconazole interaction | PG | 16 ♂HV | 19 | 30 mg CR OD 0, 400 mg ketoconazole |
| Erythromycin interaction | PG | 29 ♂HV | 18 | 30 mg CR OD 0, 400 mg erythromycin |
| Multiple dose SOL | PG | 16 ♂HV | 15 | 0, 10 mg SOL TID |
| Multiple dose IR | XO | 16 ♂HV | 36 | 2.5, 5, 10 mg IR TID |
| IR-CR in patients | XO | 30 ♂/18 ♀PTS | 8 | 2.5 mg IR TID, 15, 30 mg CR OD |
*
Median number of samples per subject. XO, Cross-over; HV, healthy volunteer; PTS, patient; PG, parallel group; SOL, solution; IR, immediate release; CR, (continuous) extended release; CRS, CR; CRM, medium CR; CRF, fast CR; OD, once daily; TID, 3×/day.