The effect of CLOBEX® Spray, % on hypothalamic-pituitary-adrenal (HPA) axis function was investigated in adults in two studies. In the first study, patients with plaque psoriasis covering at least 20% of there body applied CLOBEX® Spray, % twice daily for up to 4 weeks. 15% (2 out of 13) of patients displayed adrenal suppression after 4 weeks of use based on the Cosyntropin Stimulation Test. The laboratory suppression was transient; all subjects returned to normal after cessation of drug use. In the second study, patients with plaque psoriasis covering at least 20% of their body applied CLOBEX® Spray, % twice daily for either 2 or 4 weeks. 19% (4 out of 21) of patients treated for 2 weeks and 20% (3 out of 15) of patients treated for 4 weeks displayed adrenal suppression at the end of treatment based on the Cosyntropin Stimulation Test. The laboratory suppression was transient; all subjects returned to normal after cessation of drug use. In these studies, HPA axis suppression was defined as serum cortisol level ≤ 18 μg/dL 30-min post cosyntropin (ACTH 1-24) stimulation [see WARNINGS AND PRECAUTIONS ].
Clobetasol propionate at concentrations up to % did not increase the rate of formation of ultra violet light-induced skin tumors when topically applied to hairless mice 5 days per week for a period of 40 weeks.
Clobetasol propionate was negative in the in vitro mammalian chromosomal aberration test and in the in vivo mammalian erythrocyte micronucleus test
The effect of subcutaneously administered clobetasol propionate on fertility and general reproductive toxicity was studied in rats at doses of 0, , 25, and 50 μg/kg/day. Males were treated beginning 70 days before mating and females beginning 15 days before mating through day 7 of gestation. A dosage level of less than μg/kg/day clobetasol propionate was considered to be the no-observed-effect-level (NOEL) for paternal and maternal general toxicity based on decreased weight gain and for male reproductive toxicity based on increased weights of the seminal vesicles with fluid. The female reproductive NOEL was μg/kg/day (ratio of animal dose to proposed human dose of on a mg/m 2 /day basis) based on reduction in the numbers of estrous cycles during the pre-cohabitation period and an increase in the number of nonviable embryos at higher doses.