TABLE 9.
Clinical trial simulation results and dose escalation decisions
| Dose (mg) | % probability of any subject exceeding exposure threshold in a clinical trial |
|
|---|---|---|
| AUC0–24 | Cmax | |
| Dose escalation analysis 1a | ||
| 15 | 0 | 0 |
| 25 | 0 | 0 |
| 30 | 0 | 7 |
| 35 | 4 | 23 |
| Dose escalation analysis 2b | ||
| 25 | 0 | 5.3 |
| 30 | 3.3 | 20.3 |
| Dose escalation analysis 3c | ||
| 25 | 0.1 | 5.8 |
| 30 | 1.5 | 18 |
| Dose escalation for repeat dosed | ||
| 5 | 0 | 0 |
| 10 | 0 | 0 |
| 15 | 10 | 1.4 |
a
Data include a 5-mg single dose (n = 6) and simulation of 100 trials (n = 6/trial), with a decision for a 15-mg single dose.
b
Data include 5- and 15-mg single doses (n = 12) and simulation of 1,000 trials (n = 6/trial), with a decision for a 25-mg single dose.
c
Data include 5-, 15-, and 25-mg single doses (n = 18) and simulation of 1,000 trials (n = 6/trial), with a decision to end the single dose.
d
Data include 5-, 15-, and 25-mg single doses (n = 18) and simulation (steady state) of 1,000 trials (n = 8/trial), with a decision to initiate with 5 mg once daily.