Fifteen subjects were given medications for allergic rhinitis and asthma during the intervals between allergen challenges, and five subjects received medications for other indications. None of the subjects received steroids or cromolyn in any form.
All 13 subjects had at least a 20 percent decrease in FEV, at both screening challenges, with responses provoked at allergen concentrations ranging from 0.05 to 6.25 |xg/ml.
Figure 1 shows allergen-induced changes in FEV, for subjects after both screening challenges and challenges after administration of ICI 204,219. Table 2 summarizes bronchial challenge test results by formulation; Table 3 presents bronchial challenge test results for each of the 13 subjects. canadian health&care mall
The majority of subjects tolerated bronchoprovocation testing without a 20 percent decrease in FEV, (31 of 39 challenges). The mean (SE) log shift was 1.6 (0.23), with a 95 percent confidence interval of a 1.0 to 2.2 log shift (10- to 158-fold shift). This was a significant (p = 0.0001) shift from the screening values. No statistically significant differences were observed between formulations. Six subjects had a 20 percent decrease in FEV, at end point allergen concentrations greater than fourfold of the screen concentrations. Only two subjects had a 20 percent decrease in FEV, at end point allergen concentrations within two dilutions of their maximum screen concentrations; one of the subjects received formulation 2 (four puffs), and the other subject received formulation 3 (one puff).
Responses in seven subjects were censored (inhalation of five puffs of 100 jig/ml without a PC20) at every visit, and all other subjects had censored responses in at least one (n = 1) or two (n = 5) other periods. Thirty-one of 39 individual challenges were censored, which contributed to early termination of the study. No statistically significant treatment or sequence differences were noted for pulmonary function test results (FEV,, FVC, or FEV, percent predicted) before or after bronchoprovocation.
Plasma concentrations of ICI 204,219 indicated differences in systemic exposure. All subjects who received formulation 1 (n = 15) had detectable drug plasma concentrations 30 min and 2 h after dosing. None of the subjects who received formulation 2 (n = 15) had detectable concentrations after 30 min, and 8 had detectable concentrations after 2 h. Of the subjects receiving formulation 3 (n = 15), 2 had detectable concentrations after 30 min, and 7 had detectable concentrations after 2 h.
Figure 1. FEV, of subjects with asthma who were challenged with increasing concentrations of antigen until FEV, decreased 20 percent or the maximum allergen concentration was reached. Shaded box with dotted line = first screening period; open box with dotted line = second screening period; open triangle with solid line « challenge 30 min after receiving four actuations of formulation 1 (0.05 mg per actuation); shaded triangle with solid line = challenge 30 min after receiving four actuations of formulation 2 (0.05 mg per actuation); shaded circle with solid line = challenge 30 min after receiving one actuation of formulation 3 (0.2 mg per actuation).
Table 2—Bronchial Challenge Test Results
|Response Criteria||No. Responding (%) ■|
|rForm 1 (n = 13)||Form 2 (n = 13)||Form 3 (n = 13)|
|No 20% decrease in FEV,* 100 allergen||11(85)||9(69)||11 (85)|
|20% decrease in FEV, 100 Hg/ml allergen||1 (8)||2(15)||0 (0)|
|^ 100 ll^ml allergen||1 (8)||2(15)||2 (15)|
Table 3—Individual and Mean Bronchial Challenge Test Results
|Average PC20||Lowest PC20|
|Subject||Screen, |lg/ml||Active, fig/ml||Fold Shift|
|Log scale mean (SD)||-0.15 (0.71)||1.51 (0.95)||1.66 (0.80)|