Ciclesonide Reduces the Need for Oral Steroid Use in Adult Patients With Severe, Persistent Asthma: Safety
The investigators assessed patients for AEs; in addition, patients reported AEs in their patient diaries. Data from physical examinations and clinical laboratory tests were collected at screening and week 12. HPA-axis function was assessed at randomization and at week 12 via cosyntropin stimulation. Blood samples for serum cortisol measurements were collected before and after stimulation with low-dose (1 |j,g) cosyntropin. Fasting basal serum cortisol levels were measured at 8:15 am and 20, 30, and 60 min after stimulation with cosyntropin. Cortisol testing was performed using high-performance liquid chromatography (Waters Corporation; Milford, MA). For this study, HPA-axis function was considered normal if the basal serum cortisol level was a 5 |j,g/dL and the post-low-dose cosyntropin stimulation peak serum cortisol level was a 18 |j,g/dL; or, for women receiving oral contraceptives or hormone therapy, if low-dose peak serum cortisol levels (defined as the post-low-dose peak serum cortisol level minus the pre-low-dose serum cortisol level) were a 7 ^g/dL from the pre-low-dose cortisol level. read
A sample size of approximately 150 patients (approximately 50 in each treatment group) was needed for the study to have 90% power (with a two-sided test significance level of a = 0.05) to detect a difference of 40 percentage points in the percentage baseline to endpoint change in prednisone dose (approximately 4.8 mg) between the ciclesonide and placebo treatment groups. The primary efficacy end point was the percentage change from baseline to end point (week 12 or early termination) in prednisone dose in the intent-to-treat (ITT) population, defined as those patients who received at least one dose of the study medication and had a valid baseline and at least one post-baseline efficacy assessment. The primary efficacy end point was assessed using an analysis of covariance (ANCOVA) model. Supportive analyses of the primary efficacy end point were done to assess ANCOVA model assumptions. ANCOVA models were also used to analyze baseline to end point changes in FEV1, weekly changes from baseline for PEF measured in the morning, 24-h asthma symptom scores, albuterol use, and serum cortisol levels. Safety analyses were conducted in the safety population, which included all patients who received at least one dose of the study medication. The proportion of patients reducing or discontinuing prednisone use at study end and the changes in laboratory data were analyzed using Cochran-Mantel-Haenszel and Kruskal-Wallis tests, respectively. Analysis of withdrawal rates and the Kaplan-Meier analysis of time to withdrawal (days since date of randomization) were conducted using Fisher Exact Test and the log-rank test, respectively.