Table I.
Summary of the Observed Concentrations included in the Population PK Analysis
| Study title | Study No. | Dose (mg) | Number of subjects a | Number of subjects with only BLQ records | Number of plasma concentrations b | Number of BLQ records |
|---|---|---|---|---|---|---|
| Phase 1 studies | ||||||
| Single dose study (healthy Japanese) | 0824 V9211 | 0.1 | 6 | 0 | 108 | 6 |
| 0.3 | 6 | 0 | 108 | 6 | ||
| 1 | 6 | 0 | 108 | 6 | ||
| 3 | 6 | 0 | 108 | 6 | ||
| Multiple dose study (healthy Japanese) | 0917 V9213 | 3 | 9 | 0 | 414 | 9 |
| Mass balance study | 1016 V9215 | 2 | 12 | 0 | 307 | 86 |
| DDI study with cyclosporine (P-gp inhibitor) | 1202 V9218 | 0.4 | 13 | 0 | 260 | 14 |
| Thorough QTc study | 1204 V9219 | 0.2 | 52 | 0 | 572 | 53 |
| 1 | 49 | 0 | 539 | 49 | ||
| BA/ FE study (to-be-marketed tablet) | 1311V921A | 0.2 | 18 | 0 | 972 | 86 |
| DDI study with rifampin (CYP3A inducer) | 1403V921D | 0.2 | 14 | 0 | 280 | 20 |
| Renal impairment study | 1401V921B | 0.2 | 38 | 0 | 919 | 51 |
| Hepatic impairment study | 1402V921C | 0.2 | 24 | 0 | 480 | 27 |
| DDI study with itraconazole/ fluconazole (CYP3A inhibitors) (healthy Japanese) | 1502V921E | 0.2 | 28 | 0 | 560 | 49 |
| Phase 2 studies | ||||||
| Phase 2 OBD POC study in patients with chronic non-cancer pain | 1007 V9214 | 0.01 | 9 | 0 | 171 | 42 |
| 0.03 | 9 | 0 | 171 | 36 | ||
| 0.1 | 9 | 0 | 169 | 15 | ||
| 0.3 | 9 | 0 | 171 | 11 | ||
| 1 | 9 | 0 | 170 | 9 | ||
| 3 | 9 | 0 | 171 | 9 | ||
| Phase 2b dose finding study in patients with chronic non-cancer pain | 1107 V9221 | 0.1 | 9 | 0 | 75 | 9 |
| 0.2 | 9 | 0 | 76 | 9 | ||
| 0.4 | 10 | 0 | 79 | 10 | ||
| Phase 2b dose finding study in cancer patients | 1108 V9222 | 0.1 | 10 | 0 | 59 | 1 |
| 0.2 | 16 | 0 | 95 | 0 | ||
| 0.4 | 12 | 0 | 71 | 0 | ||
| Phase 3 studies | ||||||
| Phase 3 DBT study #1 in patients with chronic non-cancer pain | 1314 V9231 | 0.2 | 259 | 31 | 721 | 111 |
| Phase 3 DBT study #2 in patients with chronic non-cancer pain | 1315 V9232 | 0.2 | 261 | 44 | 723 | 155 |
| Phase 3 DBT Study in Japanese Cancer Patients | 1331 V9236 | 0.2 | 97 | 0 | 276 | 5 |
| Phase 3 long-term safety study in Japanese patients with chronic non-cancer pain | 1336 V9238 | 0.2 | 43 | 0 | 85 | 0 |
| Phase 3 long-term safety study, in Japanese patients with chronic non-cancer pain receiving oxycodone therapy | 1339 V9239 | 0.2 | 10 | 0 | 20 | 2 |
BA Bioavailability, BLQ Below the limit of quantification, DBT Double blind test, DDI Drug-Drug Interaction, FE Food effect, OBD Opioid-induced bowel dysfunction, POC Proof of concept
a Subjects with only BLQ records were included
b BLQ records were included