Table 2.
Summary of 24-month oral carcinogenicity study with dapagliflozin in rats
| Dapagliflozin dose (mg/kg per day): | Males | Females | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 0a (n = 70) | 0b (n = 70) | 0.5 (n = 70) | 2 (n = 70) | 10 (n = 70) | 0a (n = 70) | 0b (n = 70) | 0.5 (n = 70) | 2 (n = 70) | 10 (n = 70) | |
| C max at day 184, μg/mL | NA | NA | 0.38 | 1.29 | 8.05 | NA | NA | 0.50 | 1.84 | 8.84 |
| AUC(0–24) at day 184c, μg h/mL | NA | NA | 3.12 | 11.80 | 60.70 | NA | NA | 4.04 | 16.00 | 86.60 |
| No. survivors at termination, n (%) | 20 (29) | 22 (31) | 31 (44) | 30 (43) | 22 (31) | 28 (40) | 33 (47) | 31 (44) | 25 (36) | 27 (39) |
| Major causes of deathd, % | ||||||||||
| Chronic progressive nephropathy | 48 | 46 | 62 | 50 | 75 | 5 | 3 | 10 | 11 | 12 |
| Mammary tumor | 0 | 0 | 0 | 0 | 0 | 19 | 41 | 36 | 27 | 28 |
| Pituitary tumor | 4 | 2 | 3 | 0 | 2 | 33 | 30 | 10 | 18 | 21 |
| Other causes | 48 | 52 | 35 | 50 | 23 | 43 | 26 | 44 | 44 | 39 |
AUC (0–24) area under the plasma concentration–time curve from administration to 24 h, C max maximum observed plasma concentration, NA not applicable
aVehicle-control group
bWater-control group
cTermination occurred in weeks 89–91 for males and weeks 105–106 for females
dPercentage of deaths attributed to a specific cause