TABLE 1.
Experimental design
| Factor | Design for:
|
|
|---|---|---|
| Phase 1 | Phase 2 | |
| Purpose | Acute toxicity/PK determination | FOB evaluation (multiple-dose-level study) |
| Dose identification | ||
| Selected neurological endpoints | ||
| Dosing groups | 13.6, 24, 43, 77, 136, 242, 343, 430, 574, and 765 mg/kga | Prophylaxis dose (45 mg/kg) |
| Treatment dose (187 mg/kg) | ||
| Intermediate dose (327 mg/kg) | ||
| MTDb (574 mg/kg) (n = 8 per treatment group) | ||
| Vehicle | Corn oil (3.0 ml/kg, n = 6) | Corn oil (2.25 ml/kg, n = 8) |
a
Minimum of four rats per group for the toxicity/pharmacokinetics (PK) study, with an additional three rats for the 187-mg/kg group and an additional two rats for the 765-mg/kg group for the histology and confirmatory toxicity experiments.
b
MTD, maximum tolerated dose.