Clinical Study Of Ciclesonide Power Inhaler In The Treatment Of Mild-moderate Asthma

Background and objective：Inhaled glucocorticoids (ICS) has become the first-line drug for the treatment ofasthma[1]。The chronic airway inflammation that a variety of cells and their componentsinvolved in is the basis of asthma symptoms and airway hyper responsiveness(AHR)，andis the important reason for leading to asthma course long-term and repeated。 ICS couldinhibit any period of airway inflammation，and improve the patient’s symptoms，lungfunction and quality of life，and reduce AHR。 Ciclesonide (CIC) is an inhaledcorticosteroid and play a powerful anti-inflammatory role through the esterase hydrolysisand have been used for treatment of children (>12years old) and adult asthma over40foreign countries.。Abroad clinical trial confirmed its efficacy and satety。 To investigatethe response to CIC in asthmatic patients from han Chinese，we are authorized toconducted a Phase II clinical trial，efficacy and safety of CIC power inhaler in thetreatment of mild-moderate asthma。 Research methods:Patients≥18years of age with a history of asthma were randomized in aplacebo-controlled，double-blind, parallel group, multicenter study to CIC80μg(JiangsuZhengda Tianqing pharmaceutical Co., Ltd)，or placebo (Jiangsu Zhengda Tianqingpharmaceutical Co., Ltd) once daily for12weeks。Safety was assessed by monitoringtreatment-emergent adverse events (TEAEs)。Subjects inhaled fluticasone propionate(flixotide)(a dose of125μ g，bid) in4-weeks run-in period。In12-weeks treatment period，follow-up was performed on day0and at week2、4、6、12。The primary efficacy indexare changes of forced expiratory volume in one second (FEV1)，peak expiratory flow (PEF)and drop out rate for lack of efficacy (LOE) before and after treatment。Secondary efficacyparameters include the changes in asthma symptom scores，dose of rescue medicineuseuse，PEF（Early and late）and PEF diurnal variation rate。During the clinical trial subjectsuse Ventolin aerosol according to the need. All the participants will no longer use anyother glucocorticoids in the treatment period。The statistical analysis of the study resultswas performed according to a statistical analysis plan。Data entry and analyses werecarried out by Department of Statistics teaching and research of4th Military MedicalUniversity。The results:1.Changes in the first second forced expiratory volume (FEV1)FAS (PPS) analysis：Compared with baseline values，EV1of the test group increased by0.00±421.22(10.98±434.50) ml （p>0.05) after12-week treatment；while controlgroup decreased statistically significantly by120.72±450.49(141.85±485.20)ml (p <0.05)。The difference between groups had no statistical significance (p>0.05) accordingto FAS set analysis，but was significant statistically (p <0.05) PPS set analysis。2.Changes of Peak expiratory flow (PEF)FAS (PPS) analysis：compared with baseline values，PEF of the test group increased by7.36±87.82(11.63±91.74) ml(p>0.05) after12-week treatment；but control groupdecreased by26.96±85.99(29.92±91.70) ml(p <0.05)。Both analysis of FAS or PPS set，there was significant difference between two groups (p<0.05)。 3.The drop out rate due to lack of efficacy (LOE)FAS analysis：the drop out rate due to lack of efficacy occurred after treatment for morethan112days in test group；while less than86days in control group。there was asignificant difference between two groups by logrank test (χ2=25.63，p=0.0000)。PPS setanalysis results was similar to FAS set analysis。4.Changes of daytime and nighttime asthma symptom score：4.1Changes of daytime asthma symptomFAS (PPS) analysis：Compared with baseline values，the daytime symptom score in thetest group decreased by0.24±0.59(0.23±0.61) score after12-week treatment (P <0.05)；while the control group increased by0.18±0.80(0.19±0.85) score (P>0.05)。Thedifference between two groups was significant (p <0.05, FAS or the PPS set analysis)。4.2Changes of nighttime asthma symptomsFAS (PPS) set analysis：Compared with baseline values，nighttime symptom score in thetest group decreased by0.10±0.44(0.11±0.45)score (p <0.05) after12-weektreatment；while the control group increased by0.23±0.65(0.24±0.65)score (p <0.05)。The difference of between two groups was statistically significant (p <0.05，FAS or thePPS set analysis)。5.Use of rescue medicationFAS (PPS) set analysis：compared with the baseline value，rescue medication use in testgroup decreased by0.41±2.90(0.47±3.12) spray/day after12-week treatment (p>0.05)；while control group increased by0.06±1.15(0.06±1.24) spray/day (p>0.05)。The difference of between two groups was not statistically significant (p>0.05，FAS or thePPS set analysis)。6.Morning and evening PEF change6.1Morning PEFFAS (PPS) set of analysis：Compared with baseline values，morning PEF in the testgroup increased by17.63±53.97(20.77±56.14) L/min(p <0.05) after12-weektreatment；while control group decreased by6.70±47.07(7.20±49.12) L/min(p>0.05)。The difference of between two groups was statistically significant (p <0.05，FAS or PPS set analysis)。6.2Evening PEFFAS (PPS) set analysis：Compared with baseline values, the evening PEF in the testgroup increased by14.67±56.00(17.93±58.05) L/min (p <0.05) after12-weektreatment；while control group decreased by5.39±41.76(5.65±43.79) L/min(p>0.05)。The difference of between two groups was statistically significant (p <0.05, FAS or PPSset analysis)。7. PEF diurnal variation rate before and after treatmentFAS (PPS) set of analysis：Compared with baseline values, the PEF diurnal variationrate in the test group decreased by1.91±5.40%(2.00±5.70%)(p <0.05) after12-weektreatment；while control group increased by0.51±4.53(0.36±4.75)%(p>0.05)。Thedifference of between two groups was statistically significant (p <0.05，FAS or PPS setsanalysis)。8.Safety evaluationthere were50adverse events in37cases out of142patients of the test group，whichincidence was26.06%。23adverse events occured in16cases from71patients of thecontrol group，which incidence rate was22.54%。The difference between two groups wasnot statistically significant (P=0.6176)。In4cases there were6adverse events (2.82%)related to study drug in test group，while there were8adverse events (8.45%) related tostudy drug in control group。Incidence rate of adverse events was no significant betweentwo groups (P=0.0872)。The major adverse events included oropharyngeal discomfort，colds，skin lesions，occasional abnormal liver function。Conclusion： Production provided by Jiangsu Zhengda Tianqing pharmaceutical Co.,Ltd，ciclesonide powder for inhalation is safe and effective in the treatment of mild andmoderate asthma and can be used widely in clinical。...