Power calculations included information from ten subjects with reproducible baseline data from a previous allergen-chal-lenge study. A sample size of 24 subjects in a three-period crossover design and the reproducibility criterion for baseline eligibility allowed detection of shifts greater than two allergen dilutions in the mean response to the ICI 204,219 formulations at an a level of 0.10 with a power of 80 percent. These levels were chosen to allow a reasonable estimate of equivalence for the protective effects of the aerosol formulations, given the limited number of subjects expected to meet entrance criteria.
Analysis of variance in a three-period crossover design was used to analyze safety data (vital signs measurements, pulmonary function test results, and laboratory test results). Changes in laboratory data within treatments were assessed by paired t tests. cialis professional
Efficacy data were analyzed as showing dichotomous responses, with challenges classified as censored or not censored. A censored challenge was defined as one in which the maximum allergen-challenge concentration was given without producing a 20 percent decrease in FEV,. This dichotomous classification was used because 31 of 39 challenges were censored, and the analysis of variance technique was inappropriate. Therefore, the baseline was defined as the mean PC20 of the two screening challenges, and the response was assessed as the lowest PC20 during the randomized periods. If the responses to challenges in all three randomized periods were censored, then the maximum concentration was used as the PC20. For each patient, a paired t test of the difference in the log,0 transformed PC20 was performed. The effects of the three ICI 204,219 formulations were compared using McNemar’s test. Twenty-two subjects with mild asthma were screened for the study, and 20 subjects had reproducible responses to allergen screening challenges. Sixteen subjects (12 men and 4 women, mean age 31.7 ± 1.8 years) entered the treatment period of the study. Thirteen subjects received doses in all three study periods, one subject received doses in two study periods, and two subjects received doses in only one study period. Overall, 15 subjects received formulation 1, 15 subjects received formulation 2, and 13 subjects received formulation 3. The 13 subjects who received doses in all three study periods were included in efficacy analyses. The three subjects who did not receive each scheduled dose of ICI 204,219 were excluded from the efficacy analysis but were included in the safety analysis.