Table 1. Designs of the different studies from which plasma tififarnib data were obtained.
| Study typea | Data set (n) | Indication | Study type | Dose range (mg) | Dosing regimen | Formulation | Duration of dosing regimen | Sampling schedule |
|---|---|---|---|---|---|---|---|---|
| Phase 1 | ||||||||
| 1 [3] | Index (27) | Advanced cancer | MTD | 25–325 | b.d. | Solution | 5 consecutive days separated by a minimum of 7 days of rest period | Intensive sampling on days 0 and 5, plus 1 isolated trough sample |
| 500–1300 | s.d. | Capsule | ||||||
| 200–300 | Capsule | |||||||
| 2 [4, 15] | Index (28) | Advanced cancer | MTD | 200–300 | s.d. | Tablet | Continuous treatment | Intensive sampling on days 1, 2 and 28, plus 3–4 isolated trough samples |
| 50–500 | b.d. | Capsule | ||||||
| 3 | Index (34) | Advanced cancer | MTD | 100–850 | b.d. | Capsule | 21 consecutive days separated by a minimum of 7 days of rest period | Intensive sampling on days 0 and 21, plus 2 isolated trough samples |
| 100–850 | Tablet | |||||||
| 4 [16] | Index (25) | Advanced cancer | MTD | 100–300 | b.d. | Capsule | 21 consecutive days separated by a minimum of 7 days of rest period | Intensive sampling on days 1 and 8 |
| 100–300* | Tablet | |||||||
| 5 | Index (12) | Healthy subjects | Absolute bioavailability | 50 | s.d. | Tablet | – | Intensive sampling on two occasions |
| 25 | 1 h i.v. inf | |||||||
| 7 [6] | Index (9) | Advanced cancer | MTD | 200–500 | b.d. | Capsule | 28 consecutive days | Intensive sampling on days 1 and 28, plus 4 isolated trough samples |
| 15 | Index (31) | Advanced cancer | Bioequivalence | 200 | b.d. | Tablet | 4 consecutive days each treatment without washout period (Sequence of treatment randomized) | Intensive sampling on day 4 of each treatment |
| 240 | Continuous | i.v. Inf | ||||||
| 60–120 | b.d. | 2 h i.v. inf | ||||||
| 44 | Test (36) | Healthy subjects | Bioequivalence | 50 | s.d. | Tablet | – | Intensive sampling on two occasions |
| Phase 2 | ||||||||
| 6 [17] | Test (64) | Advanced breast cancer | Safety, efficacy | 300–400 | b.d. | Tablet | 21 consecutive days separated by a minimum of 7 days of rest period or continuously | Sparse isolated samples (week 2, 4, 8 and 12), 4–5 per subject |
| 300–400 | Capsule | |||||||
| 8 [18] | Test (19) | Small-cell lung cancer | Safety, efficacy | 400 | b.d. | Capsule | 14 consecutive days separated by a minimum of 7 days | Sparse sample, 2 samples on days 1 and 8 |
| 10 [19] | Test (28) | Advanced urothelial tract transitional cell cancer | Safety, efficacy | 300 | b.d. | Tablet | 21 consecutive days separated by a minimum of 7 days | Sparse isolated samples (days 1, 8, 15, 22, 15 (month 1), 1 (month 2)): 6 per subject |
| 12 | Test (8) | Superficial bladder cancer | Safety, efficacy | 300 | b.d. | Capsule | 6 weeks | Sparse samples: 7 samples over days 15, 29 and 42 |
| 17 | Test (242) | Acute myeloid leukaemia | Safety, efficacy | 600 | b.d. | Tablet | 21 consecutive days separated by a minimum of 7 days | Sparse isolated samples: 4 samples over days 1, 8 and 15. Intensive sampling on day 1 for a subset of 20 subjects |
| Phase 3 | ||||||||
| 9 [20] | Test (212) | Advanced colorectal cancer | Survival | 300 | bd | Tablet | 21 consecutive days separated by a minimum of 7 days of rest period | Sparse isolated samples (Days 15, 22, 1 (month 2)), 4 per subject |
| 11 [21] | Test (308) | Advanced pancreatic cancer | Efficacy | 200 | b.d. | Tablet | Continuous (1 year) | Sparse isolated samples, 4 samples over days 1, 8 and 15 |
b.d, twice a day; s.d., single dose; i.v., intravenous.
a
Reference number.
*
In combination with gemcitabine.