Once-daily ciclesonide in children: efficacy and safety in asthma. Anti‐inflammatory effects of once daily low dose inhaled ciclesonide in mild to moderate asthmatic patients Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma. Effect of ciclesonide on allergen challenge in subjects with bronchial asthma Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma. Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5'monophosphate in asthmatic patients. Four-times-a-day dosing frequency is better than a twice-a-day regimen in subjects requiring a high-dose inhaled steroid, budesonide, to control moderate to severe asthma. Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma. Once-daily ciclesonide 80 or 320 microg for 12 weeks is safe and effective in patients with persistent asthma. Maintenance of asthma control by once‐daily inhaled ciclesonide in adults with persistent asthma Ciclesonide, a novel inhaled steroid, does not affect hypothalamic-pituitary-adrenal axis function in patients with moderate-to-severe persistent asthma. Efficacy and safety of once-daily inhaled ciclesonide in adults with mild to moderate asthma: a double-blind, placebo-controlled study. Short-term lower-leg growth rate and urine cortisol excretion in children treated with ciclesonide. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. Efficacy and safety of inhaled ciclesonide compared with chlorofluorocarbon beclomethasone dipropionate in adults with moderate to severe persistent asthma. Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide. A dose-dependent effect of the novel inhaled corticosteroid ciclesonide on airway responsiveness to adenosine-5'-monophosphate in asthmatic patients. Effect of low-dose ciclesonide on allergen-induced responses in subjects with mild allergic asthma. Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma. Effect of inhaled ciclesonide on airway responsiveness to inhaled AMP, the composition of induced sputum and exhaled nitric oxide in patients with mild asthma. The effect of prescribed daily dose frequency on patient medication compliance. Similar Efficacy of Ciclesonide Once Daily Versus Fluticasone Propionate Twice Daily in Patients with Persistent Asthma Prevalence, natural history, and relationship of wheezy bronchitis and asthma in children. An epidemiological study A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma. Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.
OBJECTIVE To compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug ( CIC40 ) , 80 mug ( CIC80 ) , and 160 mug ( CIC160 ) with placebo in children with persistent asthma of all severities . STUDY DESIGN Overall , 1031 children age 4 to 11 years were r and omized into 2 identical double-blinded , placebo-controlled , parallel group studies consisting of a run-in phase followed by 12 weeks of treatment . Both studies were design ed to allow for a prespecified integrated analysis . The primary outcome variable was change in forced expiratory volume in 1 second ( FEV(1 ) ) percent predicted between baseline and study end ; treatment comparisons were assessed using analysis of covariance . Additional endpoints included asthma symptom scores , daily albuterol use , and safety , including hypothalamic-pituitary-adrenal ( HPA ) axis function . RESULTS Baseline characteristics were comparable ; 59.4 % of patients had moderate asthma , and 24.1 % had severe asthma . All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1 ) percent predicted versus placebo ( CIC40 , 11.97 ; CIC80 , 13.58 , P < .05 ; CIC160 , 14.17 , P < .01 ) . Significant improvements in asthma symptoms ( P < .01 ) and reductions in albuterol use were reported . Ciclesonide was well tolerated with no effect on HPA axis function . CONCLUSIONS In this integrated analysis , ciclesonide was effective and well tolerated in children with persistent asthma Background : Ciclesonide exhibits clinical efficacy at 160 μg ( ex‐actuator ) once daily but the anti‐inflammatory effects at this dose are not known . We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 μg once daily in the morning exhibited significant anti‐inflammatory effects BACKGROUND There are no data comparing the relative effects of high-dose ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway and systemic outcomes in patients with moderate persistent asthma . OBJECTIVE We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor ( hCRF ) and bronchial hyperresponsiveness to methacholine as the primary outcome variables , in addition to secondary outcomes of overnight 10-h urinary cortisol ( OUC ) levels , exhaled nitric oxide levels , lung function , symptoms , and quality of life . METHODS Fourteen patients with moderate persistent asthma ( mean FEV(1 ) , 67 % predicted [ prior to each r and omized treatment ] ) completed the study , which had a r and omized , double-blind , double-dummy , crossover design , per protocol . Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol , 50 mug twice daily , and montelukast , 10 mg once daily , for the 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy . Patients received 4 weeks of either CIC , 200 microg ex-valve ( 160 microg ex-actuator ) four puffs twice daily , plus FP-placebo , four puffs twice daily , or FP , 250 microg ex-valve ( 220 microg ex-actuator ) four puffs twice daily , plus CIC-placebo , four puffs twice daily . Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit , and CIC or FP was withheld for 12 h prior to each posttreatment visit . RESULTS FP , but not CIC , when compared to respective baseline values , significantly suppressed ( p < 0.05 ) plasma cortisol levels as follows : FP prior to receiving hCRF : geometric mean fold difference , 1.2 ; 95 % confidence interval ( CI ) , 1.1 to 1.3 ; CIC prior to receiving hCRF : geometric mean fold difference , 0.9 ; 95 % CI , 0.8 to 1.0 ; FP 30 min after receiving hCRF : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; CIC 30 min after receiving hCRF : geometric mean fold difference , 1.0 ; 95 % CI , 0.9 to 1.2 ; OUC after FP administration : geometric mean fold difference , 1.9 ; 95 % CI , 1.4 to 2.6 ; OUC after CIC administration : geometric mean fold difference , 1.2 ; 95 % CI , 0.9 to 1.5 . There was also a significantly lower ( p < 0.05 ) mean value for OUC levels after FP administration than after CIC administration ( geometric mean fold difference , 1.5 ; 95 % CI , 1.1 to 2.0 ) . Therapy with CIC and FP , compared to respective baselines , significantly increased ( p < 0.05 ) the provocative concentration of methacholine causing a 20 % fall in FEV(1 ) , as follows : CIC : doubling dilution difference , 0.8 ; 95 % CI , 0.1 to 1.6 ; FP : doubling dilution difference , 1.0 ; 95 % CI , 0.1 to 2.0 . It also significantly reduced ( p < 0.05 ) exhaled nitric oxide levels , as follows : CIC : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; FP : geometric mean fold difference , 1.9 ; 95 % CI , 1.3 to 2.8 . There was no effect on other secondary efficacy outcomes . CONCLUSION FP , 2,000 microg daily , but not CIC , 1,600 microg daily , significantly suppressed hypothalamic-pituitary-adrenal axis outcomes , with OUC levels being lower after FP administration than after CIC administration . Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels . The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses Background : The aim of this clinical trial was to investigate whether repeated inhalation of the new inhaled steroid ciclesonide reduces the early‐phase ( EAR ) and late‐phase ( LAR ) reactions after allergen challenge in patients with mild allergic asthma . Also , this study provides further data on safety and tolerance of ciclesonide STUDY OBJECTIVES Oral corticosteroids ( OCS ) may be associated with systemic adverse events ( AEs ) , which can be reduced by replacing OCS with inhaled corticosteroids ( ICS ) . The potential of ciclesonide , a novel ICS , to reduce OCS use in patients with severe , persistent asthma was evaluated in this study . DESIGN A phase III , 12-week , international , multicenter , double-blind , placebo-controlled , parallel-group study . PATIENTS Adult and adolescent patients ( > or = 12 years old ; n = 141 ) with severe , persistent , oral steroid (prednisone)-dependent asthma . INTERVENTIONS Patients were r and omized to receive ciclesonide ( 640 mug/d or 1,280 microg/d [ ex-actuator ] ) bid or placebo for 12 weeks . Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria . MEASUREMENTS AND RESULTS The  prednisone dose was significantly reduced by 47 % and 63 % in the groups receiving ciclesonide , 640 microg/d , and ciclesonide , 1,280 microg/d , respectively , vs an increase of 4 % in the placebo group ( both p < or = 0.0003 ) at week 12 . By week 12 , prednisone was discontinued by approximately 30 % of patients in the ciclesonide-treated groups , vs 11 % of patients in the placebo group ( both p < or = 0.04 ) . FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo ( p < 0.03 ) . The occurrence of local and systemic AEs was comparable between all treatment groups . CONCLUSION Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe , persistent asthma , while maintaining asthma control The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening . For this purpose a double-blind , r and omized , parallel group study was initiated in which 209 asthmatic patients ( forced expiratory volume in one second = 50 - 90 % predicted ) inhaled either 200 microg ciclesonide in the morning or in the evening , for 8 weeks . Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow ( PEF ) , symptoms and use of rescue medication . The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis . Ciclesonide significantly improved asthma control . Morning and evening administration was shown to be equally effective for the different spirometry variables , evening PEF , symptoms , use of rescue medication and number of asthma exacerbations . Regarding morning PEF , the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated . No relevant influence on cortisol excretion was found . Overall , the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients ' preference and individual medical needs , although evening administration may lead to a more pronounced improvement in morning peak expiratory flow The efficacy and systemic effects of ciclesonide , a novel glucocorticosteroid , inhaled via pressurized metered-dose inhaler ( pMDI ) were compared with fluticasone propionate pMDI in 26 patients with asthma , using a r and omized , double blind , placebo-controlled , double dummy , 6-period crossover study design . Treatments were placebo , ciclesonide 320 microg ( ex-actuator dose ) once daily ( o.d . ) , ciclesonide 640 microg o.d . , ciclesonide 640 microg twice daily ( b.i.d . ) , fluticasone propionate 440 microg ( ex-actuator dose ) b.i.d . , and fluticasone propionate 880 microg b.i.d . The primary variable was area under the plasma cortisol concentration-time curve over 24 h ( plasma cortisol AUC(0 - 24 ) , relative to placebo ) derived from sample s taken every 2 h , on the 9th day of treatment . Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate ( AMP ) ( relative to placebo and expressed in doubling concentrations ) . Ciclesonide did not affect 24-h cortisol secretion .  Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUC(0 - 24 ) , relative to placebo , by 29 % ( 95 % CI 15 - 41 ) and 59 % ( 95 % CI 51 - 66 ) with 440 and 880 microg b.i.d . , respectively . PC20 more than doubled with each active treatment , but no statistically significant dose-response effect could be established . It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion , that ciclesonide did not suppress cortisol secretion , and that all active treatments decreased hyperresponsiveness to AMP Fifty-three adult asthmatic subjects requiring 800 micrograms or more of inhaled beclomethasone dipropionate  were enrolled in a double-blind parallel group study of 6-month duration to compare the efficacy and side effects of inhaled budesonide in doses of 800 , 1,200 , and 1,600 micrograms given two or four times a day ( BID or QID ) . After a two-week observation period to establish baseline , subjects were given the same dose of budesonide as they would be for beclomethasone dipropionate ; however , the frequency regimen ( BID or QID ) was r and omly allocated . Subjects were asked to fill in diary cards describing their asthmatic symptoms , need for medication , and throat symptoms . They were assessed by a physician every 4 wk , at which time  spirometry  was performed . Throat swabs were done at every other monthly visit . Cortisol and response to cortisol after synthetic ACTH injection were assessed at the beginning and end of the trial . Thirty-six subjects , half in each group , completed the study . Those on the BID regimen had almost twice as many days with nocturnal asthma and cough and almost three times as many days with disability due to asthma . There were also twice as many relapses in the BID regimen as judged by the clinician . These relapses mainly occurred toward the end of the study . The maximal daily swings in peak expiratory flow rates were slightly greater in the BID group , although this difference was not physiologically significant . Spirometry , cortisol secretion , and the response after synthetic ACTH injection were not significantly different in either group from the beginning to the end of the study . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects . OBJECTIVE We sought to evaluate exercise-induced bronchoconstriction ( EIB ) as a method of determining the dose and time responses of inhaled corticosteroid therapy . METHODS In this double-blind , r and omized , cross-over study with 2 parallel arms , 4 doses of inhaled ciclesonide ( 40 microg and 160 microg or 80 microg and 320 microg ) were compared over 3 weeks of treatment . Twenty-six asthmatic subjects ( age range , 14 - 27 years ) with baseline FEV1 values of greater than 70 % of predicted value were enrolled . The primary outcome was the maximum percentage decrease in FEV1 after st and ardized exercise challenge .  RESULTS After 1 week of therapy , the mean + /- SEM reduction in maximum decrease in FEV1 in the ciclesonide 40-microg/80-microg dose group was 9 % + /- 2.6 % ( 95 % CI , 3.9 % to 14 % ) , with no additional reduction thereafter . In the ciclesonide 160-microg/320-microg dose group , there was an 8.7 % + /- 2.5 % ( 95 % CI , 3.7 % to 13.7 % ) reduction in maximum decrease in FEV1 after week 1 , which continued in a linear fashion during subsequent weeks of treatment . No difference was found between the 2 treatment arms in the temporal response of EIB to ciclesonide treatment . The maximum percentage attenuation in EIB achieved was 51.1 % + /- 7.9 % , which was achieved by using the 320-microg dose after 3 weeks of treatment . CONCLUSIONS A significant improvement in EIB was demonstrated for all doses of ciclesonide . Use of 160 microg/320 microg of ciclesonide result ed in a continuing improvement in FEV1 with time , and no plateau was seen in protective effect during 3 weeks of treatment . CLINICAL IMPLICATION S Attenuation in exercise-induced decrease can be seen as early as after 1 week of therapy with inhaled ciclesonide at doses greater than 40 microg . However , maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 microg , even after 3 weeks of therapy The efficacy and safety of ciclesonide was assessed in this r and omized , placebo-controlled study in patients with persistent asthma ( r and omized n=360 ) maintained on low to moderate doses of inhaled corticosteroids . Patients were r and omized to receive ciclesonide 80 or 320 microg ( ex-actuator doses , equivalent to 100 and 400 microg ex-valve , respectively ) or placebo once daily in the morning via metered-dose inhaler for 12 weeks . Morning peak expiratory flow was maintained throughout the treatment period in patients treated with ciclesonide and decreased significantly in patients treated with placebo ( P=0.0003 ) . Ciclesonide ( 80 and 320 microg ) significantly increased forced expiratory volume in 1s from baseline ( 0.13 and 0.19 L increases , respectively ; P<0.01 ) ; improvements were superior versus placebo ( P=0.0044 for 80 microg ciclesonide ; P<0.0001 for 320 microg ciclesonide ) . The probability of losing efficacy decreased in a dose-dependent manner ( 55 % for placebo , 38 % for ciclesonide 80 microg , 23 % for ciclesonide 320 microg ) . Asthma symptom scores and rescue medication use were unchanged with ciclesonide and significantly worsened with placebo . The incidence of adverse events was comparable in all treatment groups and no cortisol suppression was observed . Therefore , ciclesonide 80 and 320 microg administered once daily was a safe and effective maintenance treatment for patients with persistent asthma Background : Inhaled corticosteroids ( ICS ) are recommended therapy for persistent asthma , although side effects can limit appropriate use . Ciclesonide , a novel ICS , is activated in the lung , thereby reducing systemic activity and side effects . This 12‐week , double‐blind , r and omized , parallel‐group , placebo‐controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma BACKGROUND Inhaled corticosteroids ( ICSs ) reduce local airway inflammation , which is an underlying cause of asthma symptoms . However , potential systemic side effects associated with ICS use are a major concern for asthmatic patients . METHODS Adult patients ( n = 60 ; > or = 18 years of age ) with moderate-to-severe asthma were r and omized to receive 4 weeks of treatment with ciclesonide ( CIC ) , 320 microg bid ( CIC 640 ) , CIC , 640 microg bid ( CIC 1280 ) , fluticasone propionate ( FP ) , 440 microg bid ( FP 880 ) , FP 880 microg bid ( FP 1760 ) , or placebo ( PBO ) [ all doses expressed as ex-actuator ; comparable to ex-valve doses of 800 and 1,600 microg/d for CIC and 1,000 and 2,000 microg/d for FP , respectively ] . RESULTS After 29 days of treatment , CIC 640 , CIC 1280 , and FP 880 had no significant effect on the mean serum cortisol area under the curve for 0 to 24 h ( AUC0 - 24h ) . FP 1760 produced a statistically significant suppression in mean serum cortisol AUC0 - 24h compared to PBO ( p = 0.0009 ; 95 % confidence interval [ CI ] -117.5 [ corrected ] to -32.1 ) . Results obtained with cosyntropin stimulation revealed no statistically significant differences among the groups . The CIC 640 group demonstrated a significant increase compared to the PBO group in 24-h urinary cortisol levels from baseline at week 4 ( p = 0.0224 ; 95 % CI , 0.0023 to 0.0283 ) , while the other treatment groups revealed no change in this parameter . The incidence of treatment-emergent adverse events was similar in all groups , and all adverse events were mild or moderate in severity . CONCLUSION Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO BACKGROUND AND OBJECTIVE Inhaled corticosteroids are recommended as first-line therapy for the management of asthma , although side-effects may limit their use . Ciclesonide , a novel pro-drug inhaled corticosteroid , exerts potent and prolonged local anti-inflammatory effects in the lungs , and is considered to have an improved safety and tolerability profile . The aim of this study was to evaluate the efficacy and safety of ciclesonide in adult patients with mild to moderate asthma . METHODS A placebo-controlled , multicentre , r and omized , double-blind , parallel-group study was conducted . During the 4-week baseline period , patients were given 400 microg/day of beclomethasone dipropionate in a chlorofluorocarbon formulation .  After the baseline period , 311 patients were given once-daily 100 , 200 or 400 microg of ciclesonide or placebo for an 8-week treatment period without the use of a spacer . The primary efficacy variable was morning PEF . RESULTS Changes in the morning PEF ( least squares mean ) at the end of the study were 4.23 L/min ( P < 0.001 ) in the 100 microg group , 3.75 L/min ( P < 0.001 ) in the 200 microg group , -0.40 L/min ( P < 0.001 ) in the 400 microg group , as compared with -24.95 L/min in the placebo group . In the ciclesonide groups , the PEF remained at the same level as the baseline period . No large differences were observed between the placebo group and the ciclesonide groups regarding safety . CONCLUSION Once-daily administration of ciclesonide at doses of 100 , 200 or 400 microg was shown to be effective in adult patients with mild to moderate asthma .  Ciclesonide is considered to have favourable safety profiles and be well tolerated BACKGROUND Measurement of short-term lower-leg growth rate in children by means of knemometry has become established as an integral part of the available measures of systemic activity of topical steroids in children . OBJECTIVE We sought to determine the effects of clinical ly effective doses of the novel inhaled corticosteroid ciclesonide on lower-leg growth rate and hypothalamic-pituitary-adrenal axis function in children with asthma . METHODS In a double-blind , placebo-controlled , 4-period crossover study , 24 children aged 6 to 12 years sequentially received ciclesonide ( 40 , 80 , and 160 microg ) in r and omized order once daily in the evening . Each 2-week treatment period was followed by a 2-week washout period . Knemometry was performed at the beginning and end of each treatment period . Cortisol levels in 12-hour overnight urine were measured at the end of each treatment period . RESULTS No statistically significant differences were seen in lower-leg growth rates between any of the ciclesonide treatments and placebo .  Lower-leg growth rates were 0.412 mm/wk for placebo , 0.425 mm/wk for 40 microg of ciclesonide , 0.397 mm/wk for 80 microg of ciclesonide , and 0.370 mm/wk for 160 microg of ciclesonide . There was no statistically significant dose-response effect . Likewise , no statistically significant differences or dose-response effects were found for urinary cortisol adjusted for creatinine . CONCLUSION Short-term lower-leg growth rate and hypothalamic-pituitary-adrenal axis function are not affected by treatment with ciclesonide in doses intended for clinical use in children Ciclesonide is a novel inhaled corticosteroid that is converted in the lungs to its active metabolite , desisobutyryl-ciclesonide ( des-CIC ) . The aim of this study was to compare the deposition of ciclesonide , as well as its conversion to des-CIC , in the oropharyngeal cavity with fluticasone propionate ( FP ) following inhalation via hydrofluoroalkane-propelled metered-dose inhalers ( HFA-MDIs ) . Eighteen asthmatics inhaled ciclesonide 800 microg followed by FP 1000 microg or vice versa in an open , r and omized , 2-treatment , 2-sequence study design . The oropharynx was washed out immediately and at 15 , 30 , 45 , and 60 minutes after inhalation . Sample s were analyzed for ciclesonide , des-CIC , and FP using liquid chromatography with t and em mass-spectrometric detection . Concentration-time curves and area under the concentration-time curve ( AUC ) were calculated for each drug . Ciclesonide and FP were recovered in almost all sample s. Within 60 minutes after inhalation , the amounts of both ciclesonide and FP decreased sharply , and low residual levels were detected after 30 minutes . des-CIC was detected in relatively low concentrations , with maximum concentration 30 minutes following inhalation . The AUC(0 - 60 min ) for ciclesonide ( 250.4 nmol x h/L ) and des-CIC ( 37.8 nmol x h/L ) were found to be significantly lower compared with FP ( 636.2 nmol.h/L , P < .001 ) . Approximately 50 % less ciclesonide and 90 % less metabolite were present in the oropharynx compared with FP . Less than 20 % of the residual ciclesonide in the oropharynx was metabolized to des-CIC . These findings indicate that oropharyngeal deposition of ciclesonide is only half that of FP following inhalation from an HFA-MDI . Furthermore , there is little activation of ciclesonide to its active metabolite in the oropharynx , suggesting a decreased likelihood of inhaled ciclesonide-associated oropharyngeal side effects BACKGROUND AND OBJECTIVE Inhaled corticosteroids are recognized as first-line therapy in the management of asthma ; however , their use may be limited by systemic and local side-effects . Ciclesonide , a novel pro-drug inhaled corticosteroid , is activated in the lungs and is expected to have less systemic and local side-effects . This study evaluated the efficacy and safety of ciclesonide in hydrofluoroalkane ( HFA ) compared with beclomethasone dipropionate ( BDP ) in a chlorofluorocarbon ( CFC ) formulation in adult patients with moderate to severe asthma . METHODS This was a multicentre , r and omized , open-label , parallel-group comparative study . The patients were given 800 microg/day of CFC-BDP in the four-week baseline period . After the baseline period , 319 patients were r and omly allocated into three groups which , respectively , received HFA-ciclesonide 400 microg/day ( without a spacer ) , HFA-ciclesonide 800 microg/day ( without spacer ) and CFC-BDP 800 microg/day ( with spacer ) for the eight-week treatment period . The primary efficacy variable was morning PEF . RESULTS The morning PEF increased by 16.02 L/min in the 400 microg HFA-ciclesonide group , 23.98 L/min in the 800 microg HFA-ciclesonide group and 5.91 L/min in the 800 microg CFC-BDP group . Better outcomes were achieved by the use of 800 microg/day of HFA-ciclesonide compared with 800 microg/day of CFC-BDP ( P = 0.001 ) . There was no difference in adverse events between the groups . CONCLUSION In adult patients with moderate to severe asthma , 800 microg/day of HFA-ciclesonide was significantly more effective than 800 microg/day of CFC-BDP . Ciclesonide at doses of 400 microg/day and 800 microg/day was safe and well tolerated AIMS There are no data comparing the relative efficacy of hydrofluoroalkane ( HFA ) formulations of ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway hyper-responsiveness , in mild-to-moderate persistent asthma . We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP , assessing methacholine challenge , in addition to exhaled nitric oxide , lung function , diary cards and quality of life . METHODS Nineteen mild-to-moderate asthmatic patients completed the study per protocol in r and omized , double-blind , double-dummy , crossover fashion . Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study . Patients were commenced instead on salmeterol ( SM ) 50 microg one puff twice daily + montelukast ( ML ) 10 mg once daily for 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts . Patients received 4 weeks of either CIC 200 microg two puffs once daily ( 08.00 h ) + CIC-placebo ( PL ) two puffs once daily ( 20.00 h ) + FP-PL two puffs twice daily ( 08.00 h and 20.00 h ) , or FP 125 microg two puffs twice daily ( 08.00 h and 20.00 h ) + CIC-PL two puffs twice daily ( 08.00 h and 20.00 h ) . SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits . RESULTS There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution ( dd ) shift from respective baseline ; mean difference : 0.4 dd ( 95 % CI -0.4 , 1.2 ) . Moreover , there was no difference between treatments for the sequence of CIC first vs FP second ; mean difference : 0.2 dd ( 95 % CI -1.3 , 1.7 ) or FP first vs CIC second ; mean difference : 0.9 dd ( 95 % CI -0.1 , 1.8 ) . There were also no differences for other secondary outcomes between treatments , either respective or irrespective of sequence , as change from baseline . CONCLUSIONS There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma . Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated . Budesonide , a topically active corticosteroid like beclomethasone dipropionate , was given q.i.d . or b.i.d . , in the morning or A.M./P.M. , at doses of 400 , 800 , and 1600 micrograms/day . Each patient ( n = 34 ) took every treatment combination for 2 wk . The antiasthmatic and systemic effects , measured by changes in peak expiratory flow rate ( PEFR ) , blood eosinophils , and serum cortisol levels increased approximately linearly on log dose budesonide ( p less than 0.0005 ) . Systemic effects of the drug were nonsignificant at low dosage . At high dosage , morning dosing conserved hypothalamic-pituitary-adrenal function , but at the cost of a marginal reduction in efficacy ( delta PEFR , p = 0.12 ) . Having the dose frequency reduced the antiasthmatic potency of the drug , i.e. , PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage ( p = 0.002 ) . This effect was not evident when asthma was in remission but became so with asthma in relapse . Overall , the q.i.d . A.M./P.M. regimen showed the best risk-benefit relationships . The data indicate ( 1 ) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug 's long-term efficacy are likely to lead to the reverse effect , ( 2 ) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day , and ( 3 ) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs ( or apparent risk ) by simply increasing dosing frequency . These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma Inhaled corticosteroids decrease airway responsiveness in asthma partly through suppression of airway inflammation . We have previously demonstrated that inhaled budesonide reduced airway responsiveness to the mast cell stimulus adenosine-5'-monophosphate ( AMP ) to a threefold greater extent than to methacholine and sodium metabisulfite , suggesting that AMP responsiveness may be a more sensitive marker of airway inflammation and steroid action in order to assess a dose-response relationship . To investigate this , we studied the effects of three doses of the novel corticosteroid ciclesonide ( 50 micrograms , 200 micrograms , and 800 micrograms ) inhaled as a dry powder twice daily on airway responsiveness to AMP and inflammatory parameters in induced sputum . In a three-parallel-dose group , double-blind , placebo-controlled , r and omized , crossover study , with a washout period of 3 to 8 wk , a total of 29 patients with mild to moderate allergic asthma underwent AMP challenge and sputum induction before and after 14 d of treatment with ciclesonide or matched placebo . Compared with placebo , ciclesonide 100 micrograms , 400 micrograms , and 1,600 micrograms daily reduced airway responsiveness to AMP by 1.6 ( 95 % confidence interval [ CI ] , -0.1 to 3.4 , not significant [ NS ] ) , 2.0 ( 95 % CI , 0.4 to 3.6 , p < 0.05 ) , and 3.4 ( 95 % CI , 2.3 to 4 . 4 , p < 0.05 ) doubling doses , respectively , and this reduction in airway responsiveness was dose-dependent ( p = 0.039 ) . A significant reduction in the percentage of eosinophils in induced sputum was observed after 400 micrograms and 1,600 micrograms daily ciclesonide ( p < 0 . 05 ) , but this was not dose-dependent . Sputum eosinophil cationic protein ( ECP ) was significantly reduced after 400 micrograms daily ciclesonide only ( p < 0.05 ) . Thus , in patients with mild to moderate asthma , assessment of airway responsiveness to AMP , rather than inflammatory parameters in induced sputum , represents a sensitive method to evaluate a dose-response relationship of an inhaled corticosteroid and may have applications in evaluating other novel inhaled corticosteroids BACKGROUND Inhalation of allergens by sensitized patients with asthma induces reversible airway obstruction , airway hyperresponsiveness , and eosinophilic airway inflammation . Attenuation of allergen-induced bronchoconstriction and inflammation has been used to examine the efficacy of therapeutic agents such as inhaled corticosteroids in asthma . Ciclesonide , a nonhalogenated inhaled corticosteroid being developed for the treatment of persistent asthma , remains inactive until cleaved by esterases in the lung . OBJECTIVE This study examined the effect of low doses of inhaled ciclesonide , 40 microg and 80 microg , on allergen-induced bronchoconstriction , serum eosinophil cationic protein , and eosinophilic airway inflammation . METHODS Twenty-one nonsmokers with mild atopic asthma completed a multicenter , r and omized , 3-way crossover study comparing the effects of 7-day treatment of ciclesonide or placebo .  Allergen-induced responses , including the early and late fall in FEV1 , peripheral blood eosinophils , serum eosinophil cationic protein levels , and eosinophils in induced sputum were measured . RESULTS Ciclesonide 80 microg attenuated the early and late asthmatic responses , including the change in FEV1 , serum eosinophil cationic protein , and sputum eosinophils measured at 24 hours postchallenge ( P < .025 ) . Ciclesonide 40 microg attenuated the late asthmatic responses and sputum eosinophils measured at 24 hours postchallenge ( P < .025 ) , with no effect on the early allergen-induced bronchoconstriction , 24-hour FEV1 , or serum eosinophil cationic protein levels ( P < .025 ) . CONCLUSION With the exception of 24-hour postchallenge peripheral blood eosinophils , a low dose of ciclesonide , 80 microg , was effective in blocking all allergen-induced responses measured BACKGROUND Inhaled corticosteroids are recommended as first-line therapy for persistent asthma . OBJECTIVE We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma . METHODS An integrated analysis of 2 identical , multicenter , double-blind , r and omized , parallel-group , placebo-controlled trials was conducted . Patients ( n = 1015 ; aged > or = 12 years ) with mild-to-moderate asthma ( FEV1 of 60 % to 85 % of predicted value ) were r and omized to ciclesonide 80 microg ( CIC80 ) , 160 microg ( CIC160 ) , or 320 microg ( CIC320 ) , once daily ( exactuator doses ) in the morning or placebo for 12 weeks . RESULTS All ciclesonide groups showed significant improvements from baseline to week 12 in FEV1 compared with the placebo group ( CIC80 , 0.12 L [ P = .0007 ] ; CIC160 , 0.13 L [ P = .0004 ] ; and CIC320 , 0.14 L [ P < .0001 ] ) . Likewise , FEV1 percent predicted , morning and evening peak expiratory flow , 24-hour asthma symptom score , daily albuterol use , and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group . Overall  ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group . Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events , and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group . No suppression of hypothalamic-pituitary-adrenal-axis function ( as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [ 1 microg ] cosyntropin ) was observed with any dose of ciclesonide . CONCLUSIONS In this integrated analysis , ciclesonide once daily administered in the morning is effective and well tolerated To assess the efficacy of ciclesonide , a novel corticosteroid pro-drug , we compared its effect on lung function , airway responsiveness to inhaled AMP , the composition of induced sputum , and the level of exhaled nitric oxide ( NO ) with the effect of budesonide in patients with asthma . Fifteen non-smoking steroid-naive patients ( mean FEV(1 ) , 94%pred ) inhaled either 400 microg ciclesonide or 400 microg budesonide as a single morning dose for two weeks each separated by a > or =3 week wash-out period . The study was performed in a double-observer , r and omized , cross-over design . FEV(1)increased significantly during treatment with budesonide ( 3.38 vs. 3.64 l P=0,003 ) , but not after ciclesonide ( 3.60 vs. 3.69 l ) . PC(20)FEV(1)of AMP increased ( P<0,001 , each ) after both budesonide ( 4.59 vs. 32.48 mg/ml , 2.8 doubling doses ) and ciclesonide ( 3.92 vs. 20.00 mg/ml , 2.4 doubling doses ) . The percentage of sputum eosinophils was significantly reduced after ciclesonide ( 7.9 vs. 3.4 % P=0.01 ) , but not budesonide ( 6.0 vs. 4.3 % ) . After both budesonide and ciclesonide , a significant ( P<0.001 ) reduction in the level of exhaled NO occurred . In none of the parameters studied , the changes differed significantly between treatment with budesonide or ciclesonide . These data suggest that ciclesonide is equi-effective to budesonide with regard to its potency to reduce the airway responsiveness to inhaled AMP as well as airway inflammation in patients with mild asthma The objective of this study was to determine the relationship between prescribed daily dose frequency and  patient medication compliance .  The medication compliance of 105 patients receiving antihypertensive medications  was monitored by analyzing data obtained from special pill containers that electronically record the date and time of medication removal . Inaccurate compliance estimates derived using the simple pill count method were thereby avoided . Compliance was defined as the percent of days during which the prescribed number of doses were removed . Compliance improved from 59.0 % on a three-time daily regimen to 83.6 % on a once-daily regimen . Thus , compliance improves dramatically as prescribed dose frequency decreases . Probably the single most important action that health care providers can take to improve compliance is to select medications that permit the lowest daily prescribed dose frequency This 12-week , double-blind , parallel-group study compared the efficacy and safety of once daily ciclesonide and twice daily fluticasone propionate in patients aged 12–75 years with persistent asthma . Patients were r and omized to once-daily ciclesonide 80 μg ( n = 278 ) or 160 μ g ( n = 271 ) , or twice daily fluticasone propionate 88 μ g ( n = 259 ) ( all ex-actuator ) . Significant improvements from baseline were seen in all three treatment groups for forced expiratory volume in 1 second , asthma symptom scores and rescue medication use ( all p < 0.0001 ) . Asthma exacerbation rates were low ( each ciclesonide group , n = 2 ; fluticasone group , n = 1 ) . Adverse event reporting indicated good tolerability . Once daily ciclesonide 80 μg or 160 μg showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 μg in persistent asthma Three r and omly selected groups of 7-year-old schoolchildren in Melbourne with mild wheezy bronchitis , with moderate wheezy bronchitis , and with asthma were compared with a control group  , and the patients followed up until 10 years of age . Comparison showed that if there was any significant difference between the study groups and the controls it was usually present in all these study groups . It was considered that children with wheezy bronchitis and asthma were from the same population with the same underlying basic disorder , and that there was a wide spectrum in various aspects of the natural history of the disorder . About 11 % of all children aged 10 years had had some asthmatic episodes . Seventy per cent . of these children ceased having asthma before 10 years of age , while about 30 % ( 3·7 % of the whole community ) continued to have episodes . There was a highly significant correlation between early age of onset , the frequency of episodes in the first year of symptoms , and the persistence of asthmatic episodes up to 10 years of age . Ten per cent . of all children with asthmatic episodes continued to have symptoms as severely at 10 years as at an earlier period . In this group the onset of symptoms was almost always before 3 years of age , there was a high frequency of episodes in the first year of symptoms , and boys and girls were affected in the ratio of 7:3 BACKGROUND Ciclesonide is a new lung-activated inhaled corticosteroid ( ICS ) that has shown efficacy in previous placebo-controlled and comparative studies in patients with persistent asthma . It is important to compare new treatments with existing ICSs to obtain relative data concerning their efficacy and tolerability . OBJECTIVE This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma . METHODS This 12-week , r and omized study was conducted at 62 study sites across Europe . Male and female patients aged 12 to 75 years with primarily mild to moderate asthma were enrolled . This study was double blind with respect to the ciclesonide dose and open label for budesonide , as placebofor budesonide was not available . Patients were r and omly assigned to receive inhaled ciclesonide 80 or 320 microg QD ( morning ) or budesonide 200 microg BID for 12 weeks . Efficacy and tolerability assessment s were performed at weeks 0 ( baseline ) , 4 , 8 , and 12 . The primary end point was the change from baseline in forced expiratory volume in 1 second ( FEV1 ) at 12 weeks . Secondary end points were changes from baseline in morning peak expiratory flow ( PEF ) , asthma symptom scores , and rescue medication use . Tolerability was assessed throughout the study by monitoring of st and ard laboratory variables ( hematology and biochemistry ) ; physical examination , including vital signs ; reporting of adverse events ( AEs ) ; and 24-hour urinary cortisol as a measure of hypothalamic-pituitary-adrenal-axis function . RESULTS Five hundred fifty-four patients were r and omized ( 301 men , 253 women ; mean age , 41.3 years ; ciclesonide 80 microg QD , 182 patients ; ciclesonide 320 microg QD , 195 ; budesonide 200 microg BID , 177 ) . Demographic and baseline clinical characteristics , including age , sex , weight , and ( FEV1 ) were similar between the 3 groups . Compared with baseline values , week-12 FEV1 ( least squares mean [ LSM ] [ SEM ] A , + 0.267 [ 0.035 ] , + 0.256 [ 0.033 ] , and + 0.355 [ 0.034 ] L , respectively ; all , P<0.001 ) and morning PEF ( LSM [ SEM ] Delta , + 12 [ 5 ] , + 17 [ 4 ] , and + 21 [ 4 ] L/min , respectively ; all , P < or=0.008 ) were significantly improved with ciclesonide 80 and 320 microg QD and budesonide 200 microg BID . At 12 weeks , ciclesonide was found to be noninferior to budesonide with regard to mean changes from baseline in ( FEV1 ) ( intent to treat [ ITT ] : 97.5 % CI for ciclesonide 80 microg QD vs budesonide 200 microg BID , -0.192 to 0.015 ; 97.5 CI for ciclesonide 320 microg QD vs budesonide 200 microg BID , -0.200 to 0.001 ) and morning PEF ( ITT . 97.5 % CI for ciclesonide 80 microg QD vs budesonide 200 microg BID , -22 to 5 ; 97.5 % CI for ciclesonide 320 microg QD vs budesonide 200 microg BID , -17 to 10 ) . Similar findings were seen in the per- protocol population . Week-12 daily , daytime , and nighttime asthma symptom scores and rescue medication use were significantly decreased from baseline in all 3 treatment groups ( all , P<0.001 ) . The prevalences of AEs were similar across all 3 treatment groups . Week-12 mean urinary cortisol excretion was statistically similar to baseline with both ciclesonide doses ( Delta , -0.54 and + 0.16 nmol/mmol creatinine with ciclesonide 80 and 320 microg QD , respectively ) but was significantly reduced from baseline with budesonide ( Delta , -1.42 nmol/mmol creatinine ; P<0.05 ) . CONCLUSIONS The results of this study in patients with primarily mild to moderate asthma suggest that ciclesonide 80 and 320 microg QD were similar to budesonide 200 microg BID in improving pulmonary function , controlling asthma symptoms , and reducing the need for rescue medication use . Unlike budesonide , ciclesonide was not associated with significant urinary cortisol suppression in these patients BACKGROUND Despite their proven efficacy in the treatment and prevention of asthma exacerbations , current inhaled corticosteroids carry safety concerns , especially adrenal suppression . Ciclesonide ( hydrofluoroalkane propellant ) is a novel inhaled corticosteroid with few , if any , clinical adverse events . OBJECTIVE To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma . METHODS This was a double-blind , r and omized , placebo-controlled , 12-week study in adults with mild-to-moderate asthma . One hundred sixty-four patients were r and omized and treated ; 148 patients completed the study .  Fluticasone propionate ( chlorofluorocarbon propellant ) was used as an active comparator . The doses administered were 320 microg of ciclesonide once daily , 320 microg of ciclesonide twice daily , and 440 microg of fluticasone propionate twice daily , all doses ex-actuator . RESULTS For both ciclesonide groups , changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo . For the fluticasone propionate group , significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed . Oral c and idiasis rates were 2.5 % for 320-microg/d ciclesonide , 2.4 % for 640-microg/d ciclesonide , and 22.0 % for 880-microg/d fluticasone propionate . CONCLUSIONS These findings confirm the safety of ciclesonide therapy , demonstrating that at doses up to 640 microg/d , the drug does not affect sensitive markers of adrenal function
BACKGROUND Inhaled corticosteroids are an integral part of asthma management , and act as an anti-inflammatory agent in the airways of the lung .
These agents confer significant benefit in terms of symptom management and improvement in lung function , but may also cause harm in terms of local and systemic side-effects .
Ciclesonide is a novel steroid that has efficient distribution and release properties that mean it can be taken once daily , making it potentially useful in ongoing asthma management .
OBJECTIVES To assess the efficacy of inhaled ciclesonide in adults and children with chronic asthma .