ciclesonide and Asthma

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; COVID-19; Humans; Outpatients; Pregnenediones

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child Development; Child, Preschool; Fluticasone; Glucocorticoids; Humans; Infant; Mometasone Furoate; Pregnenediones

Many trials have been published comparing inhaled corticosteroid (ICS) treatments in asthma. However, mixed results necessitate the summarization of available evidence to aid in decision-making. Areas covered: This systematic review evaluated randomized controlled trials (RCTs) that compared the efficacy and safety of inhaled fluticasone propionate (FP) with other ICS including beclomethasone dipropionate (BDP), budesonide (BUD) and ciclesonide (CIC). PubMed was searched and 54 RCTs that fit pre-determined criteria were included. Endpoints evaluated included lung function, asthma symptom control, exacerbation frequency, reliever use, quality of life and steroid-related side effects. Expert commentary: Across all studies, FP was associated with either more favorable or at least similar efficacy and safety, in comparison with BDP or BUD. This observation may be related to FP's higher relative potency and almost negligible oral bioavailability. FP was comparable to CIC for efficacy. However, CIC appeared to have a smaller impact on cortisol levels than FP, which is likely due to CIC's incomplete conversion to active metabolite (des-CIC) and the lower potency of des-CIC compared with FP. Although there were no significant differences in evaluated outcomes after treatment with different ICS in the majority of studies, some observed differences could be explained by their respective pharmacodynamic and pharmacokinetic properties.

Topics: Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Pregnenediones; Randomized Controlled Trials as Topic

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchioles; Bronchodilator Agents; Disease Management; Drug Combinations; Dry Powder Inhalers; Equipment Design; Fluocinolone Acetonide; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Metered Dose Inhalers; Nebulizers and Vaporizers; Particle Size; Pregnenediones; Pressure; Pulmonary Disease, Chronic Obstructive

Inhaled corticosteroids are used as one of the first-line drug therapy in patients with asthma. However, their long-term use is associated with various oropharyngeal and systemic side and adverse effects. Design of pro-soft drug is one of the strategies, which was adopted in the design of ciclesonide for mitigation of side effects usually observed with the use of inhaled corticosteroids. Ciclesonide, a pro-soft drug, is converted to an active metabolite desisobutyryl-ciclesonide in the lungs. The anti-inflammatory effect of desisobutyryl-ciclesonide is much higher than ciclesonide, and therefore, the local effect of the metabolite is higher with lower systemic side effects. Ciclesonide has favorable pharmacokinetic and pharmacodynamic properties as inhaled corticosteroid including low oral bioavailability, high plasma protein binding and rapid systemic clearance, high pulmonary deposition and distribution and long pulmonary residence duration. These advantageous properties make ciclesonide a very effective treatment option with low side effects. Various clinical studies support safety and efficacy of ciclesonide use in mild, moderate, and severe asthma patients.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Biological Availability; Drug Design; Humans; Lung; Pregnenediones; Protein Binding; Tissue Distribution

Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth.. To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment).. We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014.. Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma.. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child.. We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated li. Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Patient Dropouts; Pregnadienediols; Pregnenediones

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians.. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma.. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014.. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma.. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation.. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision.. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses.Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence.. To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children.. We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinical study results.org were undertaken. Searches are up to date to 7 November 2012.. Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone.Ciclesonide compared to budesonide (dose ratio 1:2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group.Ciclesonide compared to fluticasone (dose ratio 1:1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00).Ciclesonide versus fluticasone (dose ratio 1:2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23).The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1:1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1:1). For ciclesonide versus fluticasone (dose ratio 1:2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1:2).. An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects.

Topics: Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Asthma severity is classified according to the level of treatment required to control symptoms. Inhaled corticosteroids are the recommended first-line therapy for the treatment of persistent asthma, and when asthma remains uncontrolled, one option is to increase the inhaled corticosteroids dose. However, there is a concomitant risk of increasing local and systemic adverse events, which may impact patient adherence and physician prescribing practices. Ciclesonide is delivered as a prodrug, has high peripheral lung deposition and high protein-binding capabilities, and is rapidly eliminated from the systemic circulation. This article reviews the use of high-dose ciclesonide in patients with severe asthma and considers whether the pharmacology of ciclesonide translates into it being an efficacious and well-tolerated option for patients requiring a step-up in their asthma treatment.

Topics: Administration, Inhalation; Animals; Anti-Asthmatic Agents; Asthma; Drug Administration Schedule; Glucocorticoids; Humans; Pregnenediones; Prodrugs; Severity of Illness Index; Treatment Outcome

Ciclesonide (CIC) is a novel inhaled corticosteroid (ICS) approved by US Food and Drug Administration for the treatment of persistent asthma, available as a pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160 mcg/activation. Ciclesonide is a corticosteroid with unique pharmacological profile including a high degree of serum protein binding, a low oral bioavailability and rapid systemic elimination. Ciclesonide is a prodrug metabolized by esterases to desisobutyryl ciclesonide (des-CIC), an active metabolite with a 100-fold greater affinity for the glucocorticoid receptor. It has shown to improve pulmonary functions, reduce the need for oral corticosteroids (OCSs) and cause lesser suppression of the hypothalamic-pituitary-adrenal axis in asthmatic patients. Clinical efficacy studies suggest that Ciclesonide is superior to placebo and is at least as effective as several active comparators with an improved therapeutic margin thereby improving the therapeutic outcome in patients of asthma.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Biological Availability; Humans; Metered Dose Inhalers; Pregnenediones; Prodrugs; Protein Binding; Receptors, Glucocorticoid

The purpose of this review is to compare and contrast the newer inhaled corticosteroid (ICS) ciclesonide with older ICSs in terms of pharmacodynamic and pharmacokinetic properties and how these affect comparative efficacy. In addition, clinical dosing strategies for ICSs including as-needed use will be explored.. Ciclesonide has demonstrated similar efficacy to that of fluticasone propionate and mometasone furoate in equipotent doses with a potentially improved therapeutic index. Once-daily administration of ICSs is generally not as effective as twice-daily. Continuous administration of ICSs does not change the natural history of asthma in either children or adults. Long-term administration of medium dose ICSs does not increase the risk of cataracts or osteopenia in children and young adults. Studies of as-needed ICSs in mild persistent asthma in adults and children have demonstrated mixed results, with some showing equal efficacy to continuous therapy and others showing superiority of continuous therapy.. Ciclesonide provides a newer ICS with favorable pharmacokinetics that may improve the therapeutic index, but assessment of its systemic effects such as growth await further studies. Continuous administration of ICSs in low to medium dose over many years is well tolerated. The use of as-needed ICSs in patients with mild persistent asthma is promising as a potential step-down therapy but awaits further studies.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aerosols; Anti-Asthmatic Agents; Asthma; Cataract; Child; Dose-Response Relationship, Drug; Drug Interactions; Growth Disorders; Humans; Infant; Nebulizers and Vaporizers; Osteoporosis; Powders; Pregnenediones; Young Adult

Asthma is a chronic disease characterized by airway inflammation and hyper-responsiveness. Inhaled corticosteroids (ICSs) constitute the guideline-recommended first-line therapy for persistent asthma. However, concerns regarding ICS-related adverse events may contribute to their underutilization by physicians and patients.. The currently available published data on the pharmacokinetic and pharmacodynamic properties, safety and efficacy of the ICS, ciclesonide, is described. Peer-reviewed publications (1996 - 2009) on the pharmacodynamic and pharmacokinetic profile, safety and efficacy of ciclesonide were reviewed.. Ciclesonide is delivered as an inactive prodrug, which is cleaved to the active molecule by intracellular esterases located in the lungs. This and other pharmacodynamic and pharmacokinetic properties may limit the amount of active molecule outside the lung and may reduce the incidence of side effects. Randomized placebo-controlled studies found that ciclesonide can initiate and maintain disease control in subjects with persistent asthma of all disease severities. Moreover, studies have found that ciclesonide is as effective as other ICSs in establishing and controlling disease symptoms. Controlled clinical trials also showed that ciclesonide is associated with minimal systemic and local treatment-related adverse events.. Published findings indicate that ciclesonide is effective at initiating and maintaining asthma control and is well tolerated, with a positive safety profile.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Administration Schedule; Humans; Hypothalamo-Hypophyseal System; Lung; Pharyngeal Diseases; Pituitary-Adrenal System; Practice Guidelines as Topic; Pregnenediones; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

To review the basis for the estimated comparative daily dosages of inhaled corticosteroids for children and adults that are presented in the National Heart, Lung, and Blood Institute's Expert Panel Report 3; in addition, the pharmacodynamic and pharmacokinetic basis for potential clinical differences among inhaled corticosteroids is discussed.. A complete MEDLINE search was conducted of human studies of asthma pharmacotherapy published between January 1, 2001, and March 15, 2006, followed by a PubMed search up until August 2008, using ciclesonide, inhaled corticosteroids, and pharmacokinetics as key words. Product information on each inhaled corticosteroid was also included.. Comparative clinical trials of inhaled corticosteroids and systematic reviews for efficacy comparisons were evaluated. Extensive literature reviews, meta-analyses, and selected clinical studies that illustrate or represent specific points of view were selected. Pharmacodynamic and pharmacokinetic data extracted from previously published reviews and specific studies were included.. Pharmacodynamic characteristics (glucocorticoid receptor binding) and lung delivery determine the relative clinical efficacy and pharmacokinetic properties (oral bioavailability, lung retention, systemic clearance) and determine comparative therapeutic index of the inhaled corticosteroids. Secondary pharmacokinetic differences (intracellular fatty acid esterification, high serum protein binding) that have been posited to improve duration of action and/or therapeutic index are unproven, and current comparative clinical trials do not support the hypotheses that they provide an advantage. Ultrafine particle meter-dose inhalers (MDIs) have not demonstrated superior asthma control or improved safety over older MDIs. All of the inhaled corticosteroids demonstrate efficacy with once-daily dosing, and all are more effective when dosed twice daily.. Current evidence suggests that all of the inhaled corticosteroids have sufficient therapeutic indexes to provide similar efficacy and safety in low to medium doses. Whether or not some of the newer inhaled corticosteroids offer any advantages at higher doses has yet to be determined.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Child; Clinical Trials as Topic; Drug Administration Schedule; Drug Delivery Systems; Drug Interactions; Humans; Nebulizers and Vaporizers; Pregnenediones; Treatment Outcome

Asthma is a chronic inflammatory disease of the airways, and inhaled corticosteroids (ICSs) are recommended as first-line therapy for persistent asthma of all severities. Ciclesonide is a novel ICS, which is administered as an aerosol solution in a metered-dose inhaler, using hydrofluoroalkane-134a as a propellant. Because of the high respirable particle fraction, high pulmonary deposition is obtained in patients, which constitutes the basis of effective therapeutic action. The parent compound, ciclesonide, is pharmacologically inactive and is activated in the target organ, the lung, to form its only pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC). Low oral deposition combined with minimal formation of des-CIC in the oropharynx may minimize the typical oropharyngeal adverse events associated with ICSs. Low oral bioavailability, rapid clearance and high protein binding reduce pharmacologically relevant systemic exposure. The unique pharmacokinetic and pharmacodynamic profile of ciclesonide offers a rationale that supports the favourable risk-benefit profile observed in clinical trials in patients with persistent asthma.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Drug Interactions; Humans; Lung; Molecular Structure; Oropharynx; Pregnenediones; Protein Binding; Radionuclide Imaging

Ciclesonide (Alvesco) is an inhaled corticosteroid used in the preventative treatment of persistent bronchial asthma in adults, adolescents and, in some countries, children. The drug is delivered by a non-chlorofluorocarbon hydrofluoroalkane (HFA) metered-dose inhaler (MDI). In the lungs, ciclesonide is converted to an active metabolite, which is responsible for the beneficial effects of the drug in patients with asthma. Ciclesonide and its active metabolite have low systemic bioavailability and therefore have a low potential to produce systemic adverse events. Inhaled ciclesonide delivered by HFA-MDI is effective in the prophylactic treatment of persistent asthma in adults, adolescents and children, and is generally well tolerated. In general, ciclesonide improves lung function and reduces asthma symptoms and rescue medication use in adults and adolescents with asthma of varying severity. The drug is generally no less effective than other inhaled corticosteroids with regard to maintaining or improving lung function and may have a more favourable tolerability profile than some other agents in this class. Ciclesonide has also shown efficacy in paediatric patients with asthma. Data on its long-term effects on other clinical outcomes, such as asthma exacerbations, would be of interest. Further comparative and long-term studies would also be beneficial in order to definitively position ciclesonide with respect to other inhaled corticosteroids. In the meantime, ciclesonide offers an effective and well tolerated first-line preventative treatment option for persistent asthma.

Topics: Administration, Inhalation; Anti-Allergic Agents; Asthma; Humans; Metered Dose Inhalers; Pregnenediones; Severity of Illness Index; Treatment Outcome

Topics: Administration, Inhalation; Adult; Anti-Allergic Agents; Asthma; Humans; Pregnenediones

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.. To assess the efficacy of inhaled ciclesonide in adults and children with chronic asthma.. We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of CENTRAL and PubMed were undertaken. The literature searches for this review are current up to June 2007.. Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with placebo, and we also included studies comparing ciclesonide at different doses.. Two authors assessed studies for inclusion in the review, extracted data independently and checked each others' work. We contacted study investigators in order to obtain additional data. Extracted data were entered into RevMan 4.2 and analysed as fixed effect mean differences for continuous data, and fixed effect risk ratios for dichotomous data.. Eighteen trials (reporting 20 study comparisons) met the review entry criteria. We report findings from 18 group comparisons where data were available (6343 participants, of whom 1692 were children). Ciclesonide versus placebo: The short duration of the included studies means that there is a lack of data with respect to the impact of ciclesonide on asthma exacerbations. At doses of 100 mcg/d or less up to 400 mcg/d in mild to moderate asthma, ciclesonide improved lung function, asthma symptoms and rescue inhaler use, compared with placebo.Dose response outcomes: Comparisons of 100 versus 200 mcg/d, 100 versus 400 mcg/d and 400 versus 800 mcg/d did not yield significant differences in lung function outcomes. Adverse event data were not available in sufficient detail to permit assessment of the safety profile of this drug.. Ciclesonide was more effective than placebo, in the short term, in improving lung function in patients with mild to moderate asthma previously treated with inhaled corticosteroids. There remain questions as to dose response, and the lack of data on the longer term impact on exacerbations and safety profile should be addressed in future studies.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Child; Chronic Disease; Humans; Placebo Effect; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both 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 is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects.. To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma.. We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007.. Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01).. The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) are the standard of care in asthma and are widely used in the treatment of patients with chronic obstructive pulmonary disease. High-dose regimens and long-term use of ICS in predisposed individuals may be associated with a variety of side effects, similar to those observed with systemic corticosteroid therapy. Side effects associated with long-term ICS use include reduction in growth velocity, cataracts, glaucoma, osteoporosis, and fractures. Fear of unwanted complications may be of concern in all patients using ICS, particularly in age- and gender-specific populations that are more prone to develop side effects or to reduce treatment adherence because of physical, behavioral, or psychological problems. In addition to concerns about ICS safety, dosing regimens that are difficult to follow may further reduce a patient's ability to comply with treatment. Ciclesonide, a new-generation ICS with unique pharmacokinetic properties, was developed to provide effective anti-inflammatory control for asthma with once-daily administration to improve patient adherence and a high safety profile to reduce the occurrence of local and systemic side effects.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Allergic Agents; Asthma; Humans; Models, Biological; Pregnenediones; Pulmonary Disease, Chronic Obstructive; Risk Assessment

Inhaled corticosteroids remain the most important therapy for chronic asthma in both adults and children. As all inhaled corticosteroids act by binding to a common glucocorticoid receptor there is little evidence of any real difference in clinical efficacy between the different inhaled corticosteroids. The main potential differences are in their propensity to cause side effects. Local side effects such as a hoarse voice do occur in a proportion of adults and there is some limited evidence that ciclesonide may cause less local side effects. In adults there is little evidence for clinically important systemic side effects from doses of inhaled steroids below 800 mcg/day (beclomethasone equivalent). Above this dose a proportion of patients may show some adrenocortical suppression, though it is unlikely to be of clinical importance. Data on bone mineral density and fracture rates is discrepant, but an overview would suggest that below 800 mcg/day there is no increase in fracture risk whereas above this dose there might be an increased fracture risk. The properties of ciclesonide would suggest that it has less propensity for systemic side effects, but large long term studies are needed to confirm this. In children using inhaled steroids at above-licensed doses reductions in short-term growth can occur, but there is little evidence for reductions in long-term growth at normal doses. At above-licensed doses, biochemical adrenocortical suppression can occur with some unusual but documented cases of clinical Addisonian crisis. Limited evidence in paediatric age groups would suggest that ciclesonide may have some advantage although it is not as yet licensed in all countries for paediatric use. Data on differences in side effects between normal and asthmatic patients, and between asthmatic patients with near-normal lung function compared to those with impaired lung function, indicate that inhaled corticosteroids (particularly fluticasone) are absorbed more in those with normal lung function; this strongly supports stepping down the inhaled steroid dose when asthma is controlled - as is recommended in asthma guidelines.

Topics: Administration, Inhalation; Adrenal Glands; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone and Bones; Dose-Response Relationship, Drug; Glucocorticoids; Growth; Hoarseness; Humans; Nebulizers and Vaporizers; Practice Guidelines as Topic; Pregnenediones

Inhaled corticosteroid therapy is an important part of asthma management.1 In England last year, over 8.4 million prescriptions for an inhaled corticosteroid (not including combination products) were dispensed in the community, at a total net cost to the NHS of around pound138 million.2 Most of these prescriptions were for beclometasone dipropionate (79% of items, pound81million); fluticasone propionate and budesonide accounted for 11% (pound30 million) and 9% (pound25 million), respectively. Around 0.3% of items were for ciclesonide (Alvesco-Altana Pharma), a newer inhaled corticosteroid. Here we consider whether ciclesonide offers any advantages over other, more established inhaled corticosteroids.

Topics: Anti-Asthmatic Agents; Asthma; Humans; Pregnenediones; Treatment Outcome

Inhaled corticosteroids (ICS) are recommended first-line therapy for patients with asthma of all severities. Prolonged exposure to high-dose ICS can cause systemic and oropharyngeal adverse events. Minimizing ICS-related adverse events by selecting an ICS with an improved safety profile may increase patients' adherence to their asthma treatment. Ciclesonide, a novel ICS currently under development, is a parent compound that is converted in the lungs by endogenous esterases to its active metabolite, desisobutyryl-ciclesonide. Reported data suggest that ciclesonide is well tolerated, with no observed effect on hypothalamic-pituitary-adrenal (HPA)-axis function and a low incidence of oropharyngeal adverse events (comparable with placebo). These safety benefits, observed in children and adults with asthma, may be due to ciclesonide's favorable pharmacokinetic/pharmacodynamic properties. The lack of HPA-axis function suppression may be due to the low oral bioavailability, high serum protein binding and rapid apparent systemic clearance reported with desisobutyryl-ciclesonide. The low incidence of oropharyngeal adverse events may be attributed to the low oral deposition of ciclesonide in the oropharynx and its limited conversion to desisobutyryl-ciclesonide. The favorable safety profile of ciclesonide suggests a conferred benefit to asthma patients treated with this novel ICS.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Child; Growth Disorders; Humans; Hypothalamo-Hypophyseal System; Mouth Diseases; Pharyngeal Diseases; Pituitary-Adrenal System; Pregnenediones

Asthma is a complex disease of the respiratory tract associated with chronic inflammation in which an intricate network of cells and cellular factors plays a major role. Asthma is one of the most common chronic diseases, with an estimated 300 million cases worldwide, imposing a considerable burden on society in morbidity, quality of life, and healthcare costs. Inhaled corticosteroids (ICSs) form the gold standard, first-line therapy in the effective management of persistent asthma and reduce morbidity and mortality from asthma. However, long-term use of high-dose ICS therapy has potential to cause systemic side effects-impaired growth in children, decreased bone mineral density, skin thinning and bruising, and cataracts. Hypothalamic-pituitary-adrenal-axis suppression, measured by serum or urine cortisol decrease, correlates with the occurrence of systemic side effects of high-dose ICSs. Therefore, cortisol may be a relevant surrogate marker to identify the potential for adverse effects from ICS therapy. Ciclesonide is a new generation ICS with demonstrable safety and efficacy in the treatment of asthma. The unique pharmacologic characteristics of ciclesonide, such as reduced local adverse effects, lack of cortisol suppression, and the option for once-daily dosing, may improve compliance with therapy and allow long-term use of ICSs without fear of systemic adverse effects.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Anti-Allergic Agents; Asthma; Bone Density; Cataract; Child; Child Development; Contusions; Glaucoma; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Osteoporosis; Pituitary-Adrenal System; Pregnenediones; Skin Diseases

Inhaled corticosteroids (ICSs) are the most potent anti-inflammatory choice for patients with asthma. Selecting the most appropriate ICS for a patient requires a thorough understanding of the pharmacologic properties of each drug.. This review details the pharmacologic properties of ciclesonide (CIC) and fluticasone propionate (FP) and reviews the available data on suppression of the hypothalamic-pituitary-adrenal axis as a measure of systemic exposure and safety profile.. Clinical studies and case reports were identified through a MEDLINE and EMBASE search of English-language articles. The databases were searched for the years 1990 to April 2005 using the terms ciclesonide, fluticasone, ICS, and adrenal suppression. All studies were clinical trials of pharmacologic properties of the ICSs in humans.. A total of 1082 articles were identified. CIC and FP are 2 of the most potent ICSs. Both have high receptor-binding affinities (12 times and 18 times that of dexamethasone, respectively), and both may provide enhanced respiratory effects through a prolonged pulmonary residence time. The CIC metered dose inhaler dispenses smaller and more highly respirable particles than FP (1.1-2.1 pm vs 2.8-3.2 microm, respectively). Therefore, a greater percentage of administered CIC is topically deposited in the lungs (52% vs 12% to 13% for FP). CIC is delivered as an inactive parent compound, which is converted to its active metabolite, desisobutyryl-CIC (des-CIC), by esterases in the airways. More than 50% of a dose of CIC is deposited and distributed evenly throughout the lungs of healthy adults; lipid conjugation in the lung also may increase lung residence time. On entering the systemic circulation, both corticosteroids are rapidly cleared by the liver (elimination half-life of 3.5 hours for CIC vs 7.8 hours for FP). However, plasma protein binding is greater with CIC/des-CIC (99%/ approximately 99%) than FP (90%), resulting in reduced amounts of des-CIC (660 pg/d) may result in adrenal suppression. CIC has not been reported to produce any significant adrenal suppression throughout its studied dose range (up to 1280 micro/d).. A review of the literature suggests that CIC, as compared with FP, achieves greater pulmonary deposition, causes fewer adverse oropharyngeal effects, deposits less biologically active drug in the systemic circulation, and has less potential for adrenal suppression.

Topics: Adrenal Cortex Hormones; Androstadienes; Asthma; Fluticasone; Half-Life; Humans; Hypothalamo-Hypophyseal System; Metered Dose Inhalers; Pituitary-Adrenal System; Pregnenediones

Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma.. We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer.. Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P < 0.05) but no significant difference in plasma cortisol response.. There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low power. These demonstrate CIC has similar effectiveness and efficacy to FP and BUD (though equivalence is not certain) and findings regarding oral deposition and HPA suppression are inconclusive. There is no direct comparative evidence that CIC causes fewer side effects since none of the studies reported patient-based outcomes.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) are considered the most effective asthma therapy, but concerns remain about side effects. The ideal ICS would have a larger therapeutic ratio than currently available agents, allowing doses to be increased but without greatly increasing the frequency or severity of adverse events. The ideal ICS would possess the following pharmacokinetic properties to maximize efficacy and minimize side effects: high pulmonary deposition, conversion to an active metabolite, high receptor potency, high pulmonary retention, low oral bioavailability, extensive metabolism, and rapid elimination. The new ICS ciclesonide has been shown to possess many of these characteristics. Ciclesonide has also been shown to improve lung function, to treat the underlying inflammation, to be effective as monotherapy in patients with persistent asthma, to have reduced side effects compared with other ICS, and to be easy to use with once-daily dosing. However, as with all new products, the advantages witnessed in clinical trials still have to be demonstrated to be beneficial long-term in general clinical use. ICS with an improved therapeutic index may have the potential to increase patient adherence, enhance the use of ICS monotherapy in the primary care setting, and increase the range of patients for whom ICS monotherapy would be appropriate.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Glucocorticoids; Humans; Pregnenediones

To review the potential systemic activity of ciclesonide and its active metabolite, desisobutyryl-ciclesonide, by evaluation of the effects on hypothalamic-pituitary-adrenal (HPA) axis function.. EMBASE and MEDLINE searches using the keyword ciclesonide, without date restrictions, were conducted to identify published articles that related to clinical trials that included ciclesonide.. The primary articles that reported systemic safety data for ciclesonide were reviewed.. Ciclesonide (320-1,280 microg/d) demonstrated no detectable, clinically relevant effect on HPA axis function as evaluated by basal cortisol excretion measurements and dynamic stimulation tests. Furthermore, ciclesonide had no effect on the normal diurnal rhythm of endogenous cortisol secretion while simultaneously improving pulmonary function and reducing bronchial hyperresponsiveness. These results suggest that ciclesonide has a low systemic activity that may be attributable to unique pharmacologic properties, including a high degree of serum protein binding, a low oral bioavailability, and rapid systemic elimination, that reduce the level of systemically available pharmacologically active drug.. Even at the higher doses used to treat more severe cases of asthma, ciclesonide was observed to have no effect on HPA axis function. These data, in conjunction with the observed clinical efficacy, suggest that ciclesonide may have an improved therapeutic margin compared with some other currently available inhaled corticosteroid treatments and, therefore, the potential to improve therapeutic outcomes.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Pregnenediones

Ciclesonide is the most recently developed inhaled corticosteroid for the treatment of asthma to enter global markets. It has been formulated as an aerosol solution in a metered dose inhaler with hydrofluoralkane. The mass median aerodynamic diameter of aerosolised ciclesonide is 1 - 2 microm, providing excellent lung deposition characteristics. Ciclesonide can undergo reversible esterification in the lungs, possibly allowing once-daily dosing, and is highly protein bound, possibly leading to reduced systemic side effects. Clinical trials suggest that ciclesonide effectively controls asthma and has a favourable safety profile.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Animals; Asthma; Bronchial Provocation Tests; Child; Humans; Hydrocortisone; Pregnenediones; Randomized Controlled Trials as Topic

The pharmacokinetic and pharmacodynamic effects of inhaled corticosteroids (ICS) have shaped the efficacy and safety of these agents in the treatment of asthma. Important pharmacokinetic and pharmacodynamic characteristics that can enhance the efficacy of ICS include small particle size, high glucocorticoid-receptor-binding affinity, long pulmonary residence time and lipid conjugation. These characteristics can increase or prolong the anti-inflammatory effects of an ICS. Important pharmacokinetic characteristics that can enhance the safety of ICS include on-site activation in the lung, low oropharyngeal exposure, negligible oral bioavailability, high protein-binding and rapid systemic clearance. The degree of oropharyngeal exposure is relevant to local side-effects, such as oropharyngeal candidiasis, dysphonia and coughing. Pharmacokinetic properties that influence the degree of systemic exposure are relevant to the pharmacodynamic effect of ICS-induced hypothalamic-pituitary-adrenal axis suppression and cortisol suppression, an indicator of potential long-term systemic side-effects, such as reduced growth velocity and bone density, fractures, and skin bruising and thinning. Therefore, significant differences in the pharmacokinetic and pharmacodynamic characteristics of the currently available inhaled corticosteroids warrant careful consideration when used in clinical practice as they may result in differences in efficacy and local and systemic safety profiles.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Biological Availability; Humans; Hydrocortisone; Pregnenediones

Review the molecular mechanisms of action, efficacy, and potential side effects associated with inhaled corticosteroids (ICS) in children with persistent asthma.. Articles in English from MEDLINE. The following terms were used: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, and oral candidiasis. Treatment guidelines, review articles, controlled trials, meta-analyses, and systematic reviews evaluating the efficacy and the adverse events of treatment with ICS were selected.. In vivo and in vitro studies show that the available ICS have different pharmacokinetic and pharmacodynamic properties that result in different action potentials. ICS also differ as to the systemic and local side effects. The bioavailability of these products is essential in order to determine the incidence of side effects. In general, ICS are capable of controlling asthma, reducing the number of exacerbations, medical consultations, hospitalizations, and the need of oral corticosteroid (applications) bursts. Improvement can also be seen in pulmonary function, especially in patients with recent onset asthma. The most documented adverse effect is transitory decrease of growth rate.. ICS are the main anti-inflammatory agent used to treat persistent asthma. When administered in low doses, they seem to be safe and effective. Patient monitoring allows for early detection of possible side effects associated with ICS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Bone and Bones; Bone Density; Budesonide; Child; Child Development; Fluticasone; Humans; Pregnenediones; Treatment Outcome

Ciclesonide is a novel inhaled corticosteroid delivered as inactive prodrug via a hydrofluoroalkane metered-dose inhaler with a deposition rate of 50 - 60 %. At its target sites, the lungs, ciclesonide is converted to an active metabolite, desisobutyryl-ciclesonide (des-CIC) [so-called on-site activation]. High lipophilicity and formation of local depot prolong pulmonary duration of action, explaining once-daily administration of ciclesonide. High protein binding and rapid clearance reduce systemic interactions. In long-term studies, ciclesonide at doses as high as 1280-1600 microg/d did not suppress biochemical markers of adrenal function. Since ciclesonide is not being activated in the oropharynx, the incidence of local adverse effects is comparable to that of placebo. Compared to other ICS, ciclesonide shows a improved therapeutic index and can, therefore, be regarded as prototype of a new, third generation of inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Humans; Pregnenediones; Prodrugs

Topics: Administration, Inhalation; Asthma; Glucocorticoids; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids with long acting beta 2-mimetics have become the mainstay of therapy for patients with asthma. The clinical and biological activity of the inhaled corticosteroids expressed as anti-inflammatory effect depends on their bioavailability, receptor affinity, lipophility, half-life terminal elimination and molecule value. Ciclesonide as a novel corticosteroid itself is inactive and used as prodrug form and needs to be cleaved by pulmonary esterases to acquire anti-inflammatory activity. Due to its quick initial activity, long clinical effectiveness in dose range of 100-800 micrograms/day, rather mild side effects, Ciclesonide is efficacious as a local potency anti-inflammatory drug.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Clinical Trials as Topic; Glucocorticoids; Humans; Pregnenediones

Inhaled corticosteroids (ICS) are a mainstay in the treatment of persistent asthma, a disease with increasing prevalence and cost implications worldwide. However, long-term use of currently available ICS is associated with local adverse effects that include hoarseness and oral candidiasis. In addition, systemic adverse effects including adrenal cortical suppression, osteoporosis, growth retardation, cataracts and glaucoma are also present. Ciclesonide is a novel ICS, which promises to provide airway anti-inflammatory efficacy that is comparable with that of the available ICS in addition to reducing the risk for local and systemic adverse events. Ciclesonide is an agent that is inactive until it reaches its target site, the lung, where it is converted to its active metabolite desisobutyryl-ciclesonide. In addition, other favourable pharmacokinetic and pharmacodynamic characteristics such as high protein binding, low oral bioavailability and rapid clearance contribute to the efficacy and improved systemic safety profile of ciclesonide.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Humans; Pregnenediones; Treatment Outcome

The adoption of inhaled corticosteroids for the treatment of asthma has resulted in significant improvements in asthma symptoms and pulmonary function, and has reduced the incidence of asthma exacerbations, emergency room visits and hospitalizations. Although inhaled corticosteroids are generally safe and well tolerated compared with oral corticosteroids, concerns remain about potential side effects. Clinically significant complications include local effects such as dysphonia and oral candidiasis and potentially serious systemic effects associated with cortisol suppression including growth retardation, glucose intolerance and increased risk for osteoporosis and fractures. These side effects are more likely to occur with long-term use and are dose related. Over the years, attempts have been made to develop corticosteroids with potent local antiinflammatory activity and an improved safety profile. Ciclesonide ([R]-11 beta,16 alpha,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with cyclohexanecarboxaldehyde 21-isobutyrate) was designed to achieve these objectives. Ciclesonide is a parent compound that is converted locally in airways by esterases to produce the active metabolite, desisobutyryl-ciclesonide (des-CIC). The active metabolite, des-CIC, has a 100-fold greater relative glucocorticoid receptor binding affinity than ciclesonide itself (relative glucocorticoid receptor binding affinities are 1200 and 12, respectively; dexamethasone reference is 100). If any ciclesonide enters the circulation, it is highly protein bound (99%) and extensively metabolized by liver oxidases, resulting in very low systemic exposure. Ciclesonide is delivered in solution form via a hydrofluoroalkane metered-dose inhaler (MDI) with a once-daily dosing schedule, which facilitates patient compliance. Clinical studies demonstrate that ciclesonide is as effective as existing "gold standard" inhaled corticosteroids for control of asthma and has a good safety profile.

Topics: Administration, Inhalation; Animals; Anti-Inflammatory Agents; Asthma; Clinical Trials as Topic; Humans; Pregnenediones

Poor adherence to medications and other aspects of the treatment plan are described in patients with asthma, especially with adverse events concerning the upper respiratory and digestive tracts. Against this background a review is presented of current knowledge about the new class of glucocorticoids (ciclesonide).

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Humans; Pregnenediones

Inhaled synthetic glucocorticosteroids are widely used in the treatment of bronchial asthma where they provide very effective first line treatment. However, a range of unwanted side effects and the often complex dosing schedules associated with these drugs frequently result in poor patient compliance. The soft drug approach has been utilised as a means of delivering these potent anti-inflammatory agents close to their site of action while reducing the degree of systemic exposure and thus limiting or eliminating the associated systemic and local side effects. A further target for pharmaceutical companies is to deliver these new treatments in a once daily formulation thus further enhancing patient compliance. While many soft steroids have failed to progress into the clinic two are meeting with some degree of success. Loteprednol etabonate, an inactive metabolite soft steroid, has been accepted for the treatment of ophthalmic disorders and is being examined in clinical trials for its effects on airway inflammation. Ciclesonide, a pro-drug soft steroid, has demonstrated efficacy without side effects in a once daily formulation in asthma patients and is being developed for the treatment of both asthma and chronic obstructive pulmonary disease with launches of a once daily inhaler formulation expected in 2003. These drugs may represent a significant step forward in the treatment of inflammatory diseases of the airways.

Topics: Androstadienes; Animals; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Glucocorticoids; Humans; Loteprednol Etabonate; Pregnenediones; Prodrugs; Pulmonary Disease, Chronic Obstructive

Ciclesonide, a non-halogenated inhaled corticosteroid with anti-inflammatory activity, is under development by Byk Gulden, Aventis and Teijin as a potential treatment for asthma [213439]. It was also being developed by Byk Gulden for chronic obstructive pulmonary disease (COPD), but no development had been reported for this indication since 1999; however, Teijin was carrying out clinical trials in this indication at the end of 2000. During 2000, Byk Gulden was carrying out phase III trials in the US and Europe and in March 2001, results were expected in the third quarter of 2001 [312399], [383726], [423659]. Two inhalant formulations (multidose powder and propellant filled) and a nasal formulation of ciclesonide are being developed by Byk Gulden for the treatment of asthma and seasonal allergic rhinitis, respectively [337147]. The compound is formulated for once-daily dosing and demonstrated good efficacy without corticosteroid-associated systemic side effects [409257]. In January 2001, Byk Gulden expected launch of a CFC-free multidose inhaler formulation in 2003 [395596]; in March 1999, launch of a nasal formulation was expected in 2004 and a multidose powder inhaler in 2005 [337147]. By September 2001, the compound was in phase III trials in the US for asthma, with a potential US launch anticipated by Aventis in 2004 [423465]. In November 2001, Aventis expected to submit an NDA to the FDA in 2003 [428057]. Teijin, which has a development and licensing agreement with Byk Gulden for the treatment of asthma and COPD in Japan, commenced phase I trials of ciclesonide in Japan in spring 1999, had completed these during 2000, and began phase II trials by September of that year [383726]. An NDA is expected to befiled in Japan in 2003. In October 2000 and April 2001, Merrill Lynch predicted peak sales of Euro400 million in 2007, with sales of Euro5 million in 2002, rising to Euro150 million in 2004 [395562], [420574]. Deutsche Bank predicted in August 2001, that sales of the product would reach Euro70 million in 2004, rising to Euro150 million in 2005 [420814].

Topics: Administration, Inhalation; Animals; Asthma; Clinical Trials as Topic; Humans; Pregnenediones; Technology, Pharmaceutical

The pathology of asthma has clarified that the inflammatory process in the pulmonary airways of the asthmatic patients determines asthma symptom activity primarily. Among the anti-inflammatory agents currently available to treat asthma, glucocorticoids are the most effective, and the topically active agents, inhaled corticosteroids (ICS) are the most efficient. In Japan, two ICS are commercially available: beclomethasone dipropionate (BDP) and fluticasone propionate(FP). Both agents have been widely used and their clinical efficacy (BDP vs FP at half the microgram dose of the BDP) are largely comparable. In order to bring asthmatic patients maximal benefits of the ICS, enhancing treatment compliance and giving educations (including how to use the ICS) are mandatory. New ICS, which have better drug delivery and be topically more potent, will be available.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Patient Education as Topic; Pregnenediones

During an earlier multicenter, open-label, randomized controlled trial designed to evaluate the effectiveness of high-dose inhaled ciclesonide in patients with asymptomatic or mild coronavirus disease 2019 (COVID-19), we observed that worsening of shadows on CT without worsening of clinical symptoms was more common with ciclesonide. The present study sought to determine if an association exists between worsening CT shadows and impaired antibody production in patients treated with inhaled ciclesonide. Eighty-nine of the 90 patients in the original study were prospectively enrolled. After exclusions, there were 36 patients each in the ciclesonide and control groups. We analyzed antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein at various time points. Changes in viral load during treatment were compared. There was no significant difference in age, sex, body mass index, background clinical characteristics, or symptoms between the two groups. Although evaluation on day 8 suggested a greater tendency for worsening shadows on CT in the ciclesonide group (p = 0.072), there was no significant difference between them in the ability to produce antibodies (p = 0.379) or the maximum antibody titer during the clinical course. In both groups, worsening CT shadows and higher viral loads were observed on days 1-8, suggesting ciclesonide does not affect clearance of the virus (p = 0.134). High-dose inhaled ciclesonide did not impair production of antibodies against SARS-CoV-2 or affect elimination of the virus, suggesting that this treatment can be used safely in patients with COVID-19 patients who use inhaled steroids for asthma and other diseases.

Topics: Asthma; COVID-19; Humans; Pregnenediones; SARS-CoV-2

Ciclesonide is a glucocorticoid prodrug, already registered for human use. Due to its mode of action and inhaled route of administration, it was considered an appropriate treatment option for horses with severe equine asthma. Although the efficacy of inhaled ciclesonide has been demonstrated in horses with asthma exacerbations under controlled mouldy hay challenge conditions, it has not yet been reported under field conditions.. To assess the effectiveness and safety of inhaled ciclesonide for the treatment of severe equine asthma.. Prospective, multicentre, placebo-controlled, randomised, double-blinded study.. The treatment success rate (as defined above) in ciclesonide-treated horses was 73.4% (80/109) after 10 (±1) days of treatment, being significantly higher than in the placebo group with 43.2% (48/111; P < 0.0001). Few systemic and local adverse events of ciclesonide were observed.. The severity of clinical signs of severe equine asthma varies over time; despite the prohibition of environmental management changes during the study, a placebo effect was also identified. This potentially contributed, in part, to the clinical improvement observed in the ciclesonide-treated group.. Ciclesonide inhalation solution administered by the Aservo

Topics: Administration, Inhalation; Animals; Asthma; Double-Blind Method; Horse Diseases; Horses; Pregnenediones; Prospective Studies; Treatment Outcome

Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control.. 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation.. There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance.. These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function.. NCT01171365. Protocol available at http://www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Drug Resistance; Female; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Pilot Projects; Prednisone; Pregnenediones; Pulmonary Alveoli; Pulmonary Eosinophilia; Quality of Life; Spirometry; Surveys and Questionnaires; Treatment Outcome

In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.. To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.. The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.. Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.. The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).. Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).. Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.. clinicaltrials.gov Identifier: NCT01248065.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Cholecalciferol; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucocorticoids; Humans; Lung; Male; Middle Aged; Pregnenediones; Treatment Failure; Vitamin D Deficiency; Vitamins

Inhaled corticosteroids (ICSs) are widely used in asthma control. Ciclesonide (CIC) is an ICS with on-site lung activation for potent anti-inflammatory activity.. This study aimed to compare the clinical benefit of CIC with budesonide (BUD) in step-down therapy.. A total of 150 patients with mild-to-moderate asthma well controlled by a combination of ICS and long-acting β2-agonist were randomised to receive either CIC 320 μg (n=75) once daily or 2 inhalations of BUD 200 μg (n=75) twice daily for 12 weeks. The forced expiratory volume in 1s (FEV1), maximum mid-expiratory flow (MMEF) and asthma control test (ACT) scores were measured. Ranked stratification of patients and physicians was assessed.. Drug adherence was significantly higher in the CIC group than in the BUD group (76.0% vs. 58.7%, P=0.03). The FEV1 and MMEF remained stable throughout the 12-week CIC treatment. In the BUD group, FEV1 significantly decreased at weeks 4 and 12. MMEF had a higher value in the CIC group than in the BUD group. Both patients and physicians ranked CIC over BUD.. CIC is more effective and has better drug adherence than BUD as step-down treatment when asthma is well controlled by combination therapy.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Medication Adherence; Middle Aged; Patient Satisfaction; Peak Expiratory Flow Rate; Pregnenediones; Severity of Illness Index; Treatment Outcome; Young Adult

Eosinophilic inflammation of the small airways is a key process in asthma that often smolders in treated patients. The long-term effects of add-on therapy on the persistent inflammation in the small airways remain unknown.. To examine the effects of add-on therapy with either ciclesonide, an inhaled corticosteroid with extrafine particles, or montelukast on small airway inflammation.. Sixty patients with stable asthma receiving inhaled corticosteroid treatment were enrolled in a randomized, open-label, parallel comparison study of 24-week add-on treatment with ciclesonide or montelukast. Patients were randomly assigned to 3 groups: ciclesonide (n = 19), montelukast (n = 22), or no add-on as controls (n = 19). At baseline and at weeks 4, 12, and 24, extended nitric oxide analysis; pulmonary function tests, including impulse oscillometry; blood eosinophil counts; and asthma control tests (ACTs) were performed.. A total of 18 patients in the ciclesonide group, 19 in the montelukast group, and 15 in the control group completed the study and were analyzed. With repeated-measures analysis of variance, ciclesonide produced a significant decrease in alveolar nitric oxide and a significant improvement in ACT scores over time. Montelukast produced significant decreases in alveolar nitric oxide concentrations and blood eosinophil counts over time and slightly improved ACT scores, whereas no such changes were observed in the control group. Alveolar nitric oxide concentrations with ciclesonide and reactance area at low frequencies with montelukast produced greater improvements over time compared with control.. Ciclesonide add-on therapy and montelukast add-on therapy may act differently, but both separately can improve small airway abnormalities and provide better asthma control.. umin.ac.jp/ctr Identifier: UMIN000001083.

Topics: Acetates; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Cell Count; Cell Movement; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Humans; Male; Middle Aged; Nitric Oxide; Pregnenediones; Pulmonary Alveoli; Quinolines; Respiratory Function Tests; Sulfides

Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta2-agonist. The present study was designed to evaluate the efficacy of a newly developed fixed combination of ciclesonide and formoterol in comparison to the marketed fixed combination of fluticasone and salmeterol in patients with moderate asthma. This was a phase II, multi-centre, randomized, parallel-group, double-blind, double-dummy study. After a 2-week run-in period, 160 patients with moderate asthma were randomized to a 6-week treatment with ciclesonide/formoterol 320/9 μg bid (CIC/F) or fluticasone propionate/salmeterol 250/50 μg bid (FP/S), both delivered as powder formulations. The primary outcome FEV1 increased during treatment by 0.356 L in the CIC/F group and by 0.288 L in the FP/S group (p < 0.0001). The increases were statistically significant and clinically relevant. The between-treatment analysis demonstrated non-inferiority of CIC/F to FP/S treatment (p < 0.0001). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. No differences were observed between treatments in the frequency of adverse events and overnight urinary cortisol/creatinine ratio. The studied fixed combination of ciclesonide/formoterol is not inferior to the marketed fixed combination of fluticasone/salmeterol in terms of efficacy and tolerability.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Austria; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Germany; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones; Treatment Outcome; Young Adult

We compared titrating inhaled corticosteroid (ICS) against mannitol airway hyperresponsiveness (AHR) or a reference strategy (control) based on symptoms, reliever use, and lung function in primary care.. One hundred sixty-four patients with persistent asthma were randomized in parallel group fashion following an initial ICS tapering. Subsequent ICS doses (as ciclesonide) were titrated against either the provocative dose of mannitol causing a 10% fall in FEV(1) (PD(10)) (AHR strategy) or a control group (reference strategy) over a 1-year period.. One hundred nineteen participants (n = 61 AHR, n = 58 control) completed the study. Time to first mild exacerbation was not significantly different: hazard ratio, 1.29; 95% CI, 0.716-2.31; P = .40. Although there were 27% fewer total number of mild exacerbations over 12 months in AHR vs control groups (n = 84 vs n = 115, P = .03), there was no difference in severe exacerbations (n = 12 vs n = 13). No other significant differences were seen between groups with the exception of mannitol PD(10) and ICS dose. There was a 1.52 (95% CI, 0.61-2.42; P = .001) doubling dose difference in mannitol PD(10) between AHR vs control groups. The final mean daily ciclesonide dose was higher (P < .0001) in AHR vs control groups (514 μg vs 208 μg), with no associated significant suppression of overnight urinary cortisol/creatinine. Significant improvements were seen within the AHR group but not the control group for the provocative concentration of methacholine causing a 20% fall in FEV(1) (P < .05), salivary eosinophilic cationic protein (P < .05), exhaled nitric oxide (P < .05), symptoms (P < .005), and reliever use (P < .001).. Mannitol challenge was well tolerated in a primary care setting. Using mannitol resulted in exposure to a higher dose of ciclesonide, which was associated with equivocal effects on exacerbations without associated adrenal suppression. Large-scale trials using mannitol in patients with more severe disease may now be warranted to further define its role.. ClinicalTrials.gov; No.: NCT01216579; URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Mannitol; Middle Aged; Pregnenediones; Prospective Studies; Treatment Outcome

In asthmatic patients receiving long-term inhaled corticosteroid therapy, there are concerns regarding the potential for developing systemic adverse effects on bone metabolism, possibly even in the absence of adrenal suppression.. The aim of this study was to investigate whether exposure to inhaled ciclesonide at high vs. low doses over 1 yr causes any significant systemic adverse effect on sensitive biomarkers of bone turnover in asthmatic patients.. Post hoc analysis of stored samples was performed in a subgroup of patients from a prospective, randomized parallel group trial with 1 yr follow-up.. We conducted a primary care study in Tayside, Scotland.. A total of 164 mild-moderate persistent asthmatics aged 18-65 yr with evidence of airway hyperresponsiveness using mannitol bronchial challenge were enrolled into the original study. Of the 119 completed patients per protocol, 100 participants had bone marker samples available for analysis.. Ciclesonide was titrated to control persistent asthma against either mannitol bronchial challenge [airway hyperresponsiveness (AHR) strategy] or a control group (based on symptoms, reliever use, and pulmonary function) over 1 yr.. We measured markers of bone formation [amino-terminal propeptide of type I collagen (PINP), amino-terminal propeptide of type III collagen (PIIINP)], resorption [carboxy-terminal telopeptide of type I collagen (ICTP), type I collagen cross-linked C-telopeptide (CTx)], and adrenal suppression (overnight urinary cortisol/creatinine ratio) at 0 and 12 months.. Mean ciclesonide doses after 12 months were: AHR, 507 μg/d (n = 50); and controls, 202 μg/d (n = 50) (P < 0.00001). There were no significant differences between AHR and control groups either at baseline or after 12 months in PINP, PIIINP, ICTP, or CTx; or in ratios of bone turnover as PINP/ICTP, PIIINP/CTx, or overnight urinary cortisol/creatinine ratio.. Higher doses of inhaled ciclesonide do not adversely affect sensitive markers of bone turnover in persistent asthmatics over 12 months.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Biomarkers; Bone Remodeling; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pregnenediones; Prospective Studies; Treatment Outcome; Young Adult

Ciclesonide (CIC) is a highly safe, inhaled corticosteroid (ICS) that is converted into a pharmacologically active metabolite (des-isobutyryl-ciclesonide); this metabolite, in turn, exerts a local anti-inflammatory effect on lung tissue. The present study was undertaken to analyze the pharmacokinetics of des-isobutyryl-ciclesonide in the serum of Japanese children with bronchial asthma treated by repeated doses of CIC and to compare the data thus obtained with those obtained for Caucasian children with bronchial asthma.. Eight Japanese children with bronchial asthma were treated for 7 days with CIC-hydrofluoroalkalane (CIC-HFA) 200 μg/day administered by a metered-dose inhaler. The study was designed to assess the pharmacokinetics after 7-day repeated administration by which the steady state can be achieved, based on the results of an earlier study involving healthy Japanese adult males who received 7-day repeated administration of CIC-HFA. Blood was sampled at multiple time points on Day 7 of treatment for measurement of the serum des-isobutyryl-ciclesonide level.. The pharmacokinetic parameters (AUC from time zero to last observed concentration [AUC(t)], AUC over the dosage interval τ at steady state [AUC(ss)], maximum concentration [C(max)], and terminal elimination half-life [T(1/2)]) and the temporal changes in the serum levels of des-isobutyryl-ciclesonide after repeated administration of CIC-HFA (200 μg/day) in Japanese children with bronchial asthma differed only slightly from those in Caucasian children with bronchial asthma. No serious adverse events were noted during the study period. Additionally, no abnormalities were detected in the serum cortisol level, other laboratory parameters, or vital signs.. Our results suggest that there is little difference in the pharmacokinetics of des-isobutyryl-ciclesonide up on repeated administration of CIC-HFA between Japanese and Caucasian children with bronchial asthma. And our study suggests that CIC-HFA (200 μg/day, once daily) can be administered safely for 7 days, without raising any safety concerns.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asian People; Asthma; Child; Child, Preschool; Female; Humans; Japan; Male; Metered Dose Inhalers; Pregnenediones; Reproducibility of Results; Treatment Outcome

Patients with mild persistent asthma constitute about 70% of the asthma population; thus, it is important to know which first-line treatment is best for the management of mild asthma. We compared benefits of first-line treatment with ciclesonide and a combination of fluticasone and salmeterol in patients with mild asthma.. Patients aged 12 to 75 years with mild persistent asthma were enrolled in a randomized, double-blind, placebo-controlled study. After run-in, patients were randomized to ciclesonide 160 μg once daily (CIC160), fluticasone propionate/salmeterol 100/50 μg bid (FP200/S100), or placebo for 52 weeks. The primary variable was time to first severe asthma exacerbation; the coprimary variable was the percentage of poorly controlled asthma days. Patients recorded asthma symptoms and salbutamol use in electronic diaries and completed a standardized version of the Asthma Quality of Life Questionnaire.. Compared with placebo, the time to first severe asthma exacerbation was prolonged, and lung function was improved with FP200/S100 treatment (P = .0002) but not with CIC160. Both CIC160 and FP200/S100 provided significantly fewer poorly controlled asthma days than placebo (P ≤ .0016 for both active treatments). Moreover, both active treatments provided significantly more asthma symptom-free days (P ≤ .0001), rescue medication-free days (P = .0005, one-sided), and days with asthma control (P ≤ .0033). Overall Asthma Quality of Life Questionnaire scores were significantly higher in both active treatment groups than placebo (P ≤ .0017).. In mild asthma, FP200/S100 prolonged time to first severe asthma exacerbation, and CIC160 and FP200/S100 were clinically equieffective for most measures of asthma control.. ClinicalTrials.gov; No.: NCT00163358; URL: www.clinicaltrials.gov.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Placebos; Pregnenediones; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome

Few large-scale studies have examined inhaled corticosteroid treatment in preschool children with recurrent wheeze. We assessed the effects of ciclesonide in preschool children with recurrent wheeze.. We included children 2-6 yrs with recurrent wheeze and a positive asthma predictive index or aeroallergen sensitization to, excluding patients with episodic viral wheezing. After a 2-4-week baseline period, patients with ongoing symptoms or rescue medication use were randomised to once-daily ciclesonide 40, 80, 160 μg or placebo for 24 weeks.. The number of wheeze exacerbations requiring systemic corticosteroids was unexpectedly low in all groups: 25 (10.2%) in placebo group, as compared to 11 (4.4%), 18 (7.3%), and 17 (6.7%) in ciclesonide 40, 80, and 160 μg, respectively. The difference in time to first exacerbation was not significantly different between groups (p = 0.786), but the difference in exacerbation rates between placebo and the pooled ciclesonide groups was (p = 0.03). Large and significant (p < 0.0001) improvements in symptom scores and rescue medication use occurred in all groups, including placebo. Improvements in FEV(1) and FEF(25-75) (measured in 284 4-6 yr olds) were larger in the ciclesonide than in the placebo group. No differences in safety parameters (adverse events, height growth, serum and urinary cortisol levels) between ciclesonide and placebo were observed.. In preschool children with recurrent wheeze and a positive asthma predictive index, ciclesonide modestly reduces wheeze exacerbation rates and improves lung function. A large placebo response and unexpected selection of patients with mild disease may have affected outcomes, highlighting the heterogeneity of preschool wheezing disorders.

Topics: Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Child; Child, Preschool; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Predictive Value of Tests; Pregnenediones; Respiratory Sounds; Treatment Outcome

Measurement of short-term lower-leg growth rate in children by knemometry has become established as an integral part of the available measures of systemic activity of inhaled corticosteroids (ICS) in children. The aim of this study was to compare the effects of the novel ICS ciclesonide (CIC) and the ICS fluticasone propionate (FP) on lower-leg growth rate and hypothalamic-pituitary-adrenal-axis function in children with mild asthma. In a double-blind, placebo-controlled, three-period crossover study, 28 children, aged 6-12 yr, sequentially received daily doses of CIC 320 μg, FP 375 μg (330 μg ex-actuator) and placebo via a spacer in a randomized order. Each 2-wk treatment period was followed by a 2-wk washout period. Knemometry was performed at the beginning and end of each treatment period. Cortisol levels in 12-h overnight urine were measured at the end of each treatment period. No statistically significant differences were seen in lower-leg growth rates between CIC (0.30 mm/wk) and placebo (0.43 mm/wk) treatments. Lower-leg growth rate during FP treatment (0.08 mm/wk) was significantly reduced compared with both placebo [least squares (LS) mean: -0.35 (95% CI: -0.53, -0.18; p = 0.0002)] and CIC [LS mean: -0.23 (95% CI: -0.05, -0.40; p = 0.0137)]. Cortisol levels in 12-h overnight urine were significantly lower in the FP group when compared with CIC (p < 0.05); however, there were no statistically significant differences between each of the active treatments and placebo. CIC had no significant effect on lower-leg growth rate in children aged 6-12 yr with mild asthma. In contrast, a similar dose of FP significantly reduced lower-leg growth rate compared with placebo and CIC.

Topics: Androstadienes; Asthma; Child; Disease Progression; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leg Bones; Male; Pituitary-Adrenal System; Pregnenediones; Time Factors

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but conventional ICS may have limited effectiveness in inflammation and patency of small airways. Ciclesonide is delivered and deposited in the peripheral region of the lung as a small particle corticosteroid. The aim of the study is to compare the effects of ciclesonide with fluticasone propionate on small airway function in asthma.. Thirty mild persistent asthma patients treated with 200 microg of fluticasone propionate were randomized to receive either ciclesonide 200 microg once daily or fluticasone propionate 100 microg twice daily for 8 weeks. Small airway function was assessed by impulse oscillometry (IOS) and percentage of eosinophil induced sputum.. We observed that ciclesonide significantly improved IOS measured resistance of small airways (R5-R20; p<0.05), distal reactance (X5; p<0.01), reactance area (AX; p<0.01), and decreased late-phase sputum eosinophil level (p<0.01) compared with fluticasone propionate. There were no significant changes in spirometry indices in either group during the study.. These findings suggest that ciclesonide improves small airway function and inflammation compared with fluticasone propionate in mild asthma. This study provides evidence that IOS and late-phase induced sputum allows detection of changes in the small airways that can not be detected by spirometry.

Topics: Adult; Airway Resistance; Androstadienes; Asthma; Cell Count; Cell Movement; Eosinophils; Female; Fluticasone; Humans; Male; Middle Aged; Oscillometry; Pregnenediones; Spirometry; Sputum

Inhaled corticosteroids, such as fluticasone propionate (FP) and ciclesonide (CIC), are commonly used for the treatment of asthma. The objectives of this study were to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of FP and a pharmacologically active metabolite of CIC (desisobutyryl-ciclesonide [Des-CIC]) using a nonlinear mixed-effects modeling approach, to investigate selected covariate effects on PK and PD parameters of FP and Des-CIC, and to assess the systemic effects of FP and CIC on serum cortisol suppression in patients with persistent asthma. This was a randomized, double-blind, placebo-controlled, double-dummy, 5-period, crossover, multicenter clinical study. A total of 32 patients were enrolled and given basic asthma medication (salmeterol 50 µg twice per day [BID] and CIC 160 µg daily in the evening) through the entire study. During crossover periods, patients were given placebo or CIC 160 µg BID (ex actuator), CIC 320 µg BID (ex actuator), FP 220 µg BID (ex actuator), or FP 440 µg BID (ex actuator). The FP and Des-CIC PK were described using a 1-compartment and a 2-compartment linear model with first-order absorption process. The FP population PK parameter estimates of the first-order rate constant, relative clearance, and volume of distribution were 4.07 1/h, 890 L/h, and 9800 L, respectively. The Des-CIC PK parameter estimates of the first-order absorption rate constant were 2.63 1/h, clearance 202 L/h (non-CIC treatment) or 271 L/h (CIC treatment), and volume of distribution 947 L. Gender was a significant covariate on the maximum cortisol release rate (male, 3440 µg/h; female, 4310 µg/h). The CIC showed the least serum cortisol suppression of the tested dosing regimens.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Area Under Curve; Asthma; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Half-Life; Humans; Hydrocortisone; Male; Middle Aged; Pregnenediones; Salmeterol Xinafoate; Sex Factors

To compare the efficacy of ciclesonide (80 microg/day) with fluticasone propionate (200 microg/day) in mild to moderate persistent asthma.. Patients aged 12-75 years and previously treated with low doses of inhaled corticosteroid (fluticasone propionate 250 microg/day or equivalent) entered a 2-4 week run-in period during which only rescue medication was permitted. For inclusion into the double-blind, 24-week treatment period, patients had to show a forced expiratory volume in 1s (FEV(1)) of 61-90% predicted and a decrease in FEV(1) during run-in of >or=10%. Patients (n = 480) were randomized to ciclesonide 80 microg (ex-actuator) once daily in the evening or fluticasone propionate 100 microg (ex-valve) twice daily. The primary efficacy variable was the change from baseline in FEV(1). Secondary efficacy variables included asthma control and asthma-specific quality of life.. Both treatments significantly increased FEV(1) and other lung function variables from baseline (p < 0.0001, both groups, all variables). The least squares mean increases in FEV(1) were 0.46L (ciclesonide) and 0.52L (fluticasone propionate); non-inferiority of ciclesonide to fluticasone propionate was demonstrated (p = 0.0002, per-protocol analysis). Five patients in each group experienced asthma exacerbations. Improvements in the percent of days with asthma control (days with no asthma symptoms and no use of rescue medication) and asthma-specific quality of life were comparable between treatments.. The study confirmed similar efficacy of ciclesonide 80 microg once daily and fluticasone propionate 100 microg twice daily in mild to moderate persistent asthma. The low dose of ciclesonide was efficacious during long-term treatment. EudraCT number: 2004-001072-39.

Topics: Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Quality of Life; Respiratory Function Tests; Surveys and Questionnaires; Treatment Outcome; Young Adult

Patient-reported outcomes provide new insights into the dynamics of asthma management. Further to asthma control and quality of life, self-reported side effects of treatment can be assessed with the validated Inhaled Corticosteroid Questionnaire (ICQ).. To compare patient-reported side effects between the inhaled corticosteroids ciclesonide and fluticasone propionate.. Patients with moderate or moderate-to-severe asthma, pre-treated with a constant dose and type of medication, were randomized in three separate studies: 1) once daily ciclesonide 320 μg (n = 234) or twice daily fluticasone propionate 200 μg (n = 240); 2) twice daily ciclesonide 320 μg (n = 255) or twice daily fluticasone propionate 375 μg (n = 273); and 3) twice daily ciclesonide 320 μg (n = 259) or twice daily fluticasone propionate 500 μg (n = 244). Patients rated the side effect questions of the 15 domain ICQ on a 7-point Likert scale (0 = not at all, 6 = a very great deal) during scheduled visits.. The majority of side effect scores remained similar with ciclesonide but worsened statistically significantly with fluticasone propionate from baseline to the end of the study in within-treatment analyses. In between-treatment analyses of studies 1 and 3 ciclesonide significantly improved total side effect scores (p < 0.025) and 14 out of 30 individual local and systemic domain scores (p < 0.025) compared with fluticasone propionate. In Study 2, although ciclesonide improved the majority of scores compared with fluticasone propionate only 'oropharyngeal itching' reached statistical significance (p < 0.025, one-sided).. Patient-perceived side effects differ depending on the type of inhaled corticosteroids used. Patients with moderate-to-severe asthma report less intense side effects assessed with ICQ with ciclesonide than with fluticasone propionate.. The reported trials were completed before July 1 2005 and, therefore, are not registered.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchoconstrictor Agents; Child; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of three doses of ciclesonide (with or without spacer) in children with persistent asthma.. This was a multicentre, double-blind, placebo-controlled, 12-week study of ciclesonide 40, 80 or 160 μg (once daily pm). Children (6-11 years) were randomised 1:1 to treatment via a metered dose inhaler (MDI) or MDI plus spacer. The primary variable was change from baseline in mean morning peak expiratory flow (PEF). Secondary variables included: time to first lack of efficacy (LOE), asthma control, forced expiratory volume in 1 s (FEV(1)), asthma symptom score and quality of life (QoL). Safety assessments included: adverse events (AEs), urinary cortisol excretion and body height.. In total, 1073 children received treatment. At endpoint, mean morning PEF significantly improved with all doses of ciclesonide vs. placebo. There was no difference over placebo in time to first LOE, but ciclesonide was superior to placebo on asthma control, symptom score, FEV(1) and QoL. There were no differences between the spacer or non-spacer subgroups. The incidences of AEs were comparable between treatment groups (approximately 35%) and there were no between-group differences in body height or urinary cortisol.. Ciclesonide 40-160 μg once daily is effective and well tolerated in children with persistent asthma; its efficacy and safety are unaffected by the use of a spacer. clinicaltrials.gov registration number: NCT00384189.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Body Height; Child; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Metered Dose Inhalers; Pregnenediones; Respiratory Function Tests; Treatment Outcome

To investigate the efficacy and safety of ciclesonide in patients with severe asthma over a 1-year period.. Patients aged 18 - 75 years with persistent asthma were enrolled in a 12-week, double-blind, randomized study and treated with ciclesonide 320 or 640 μg twice daily (b.i.d.) with the option of continuing in a 40-week extension phase (EP).. Change in morning peak expiratory flow (PEF) from baseline to 12 weeks and safety over 1 year.. 365 patients were randomized and 275 continued into the EP. During 12 weeks' treatment, morning peak expiratory flow significantly increased by 16 l/min (p < 0.001) and 14 l/min (p = 0.001) in the 320 and 640 μg b.i.d. groups, respectively. Both doses significantly reduced total asthma symptom scores by 0.29 (p < 0.0001). In both groups, the incidence of adverse effects (AEs) was low and mean cortisol levels in serum and urine were not suppressed during the EP.. Ciclesonide 320 μg b.i.d. sustained lung function and asthma symptoms in patients with severe asthma over 12 weeks' treatment, and maintained lung function during a 40-week EP; ciclesonide 640 μg b.i.d. did not provide additional benefits. Long-term use of ciclesonide was not associated with increased local AEs or negative effects on cortisol levels.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Pregnenediones

Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning.. This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the efficacy and safety of ciclesonide with fluticasone propionate in children with mainly moderate and severe persistent asthma.. Seven hundred and forty-four patients (aged 6-11 years) were randomized to ciclesonide (80 or 160 microg once daily) or fluticasone propionate (88 microg twice daily), following a 2-4-week run-in. Efficacy measurements included forced expiratory flow in 1s (FEV(1)), morning peak expiratory flow (PEF), asthma symptom scores, rescue medication use and quality of life. Systemic effect was assessed by 24-hour urine free cortisol adjusted for creatinine.. FEV(1) and morning PEF increased from baseline in all groups (p<0.0001). Ciclesonide 160 microg was not inferior to fluticasone propionate 176 microg for FEV(1) (p=0.0030, one-sided). In all groups, asthma symptom score sums and rescue medication use significantly improved (p<0.0001). The percentages of asthma symptom-, rescue medication- and nocturnal awakening-free days were high, with no significant differences between treatments. Quality of life scores improved with all treatments (p<0.0001). A significant dose-response occurred between low and higher doses of ciclesonide for exacerbations and asthma control definitions. The incidences of adverse events were comparable across treatments. Urine free cortisol levels decreased significantly with fluticasone propionate (p=0.0103), but not with ciclesonide.. Once-daily ciclesonide has a clinical effect similar to that of fluticasone propionate, but does not suppress cortisol excretion, in children with moderate and severe asthma.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchoconstrictor Agents; Child; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Lung; Male; Methacholine Chloride; Pregnenediones; Quality of Life; Treatment Outcome

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1) and salmeterol 50 microg twice daily, in 32 patients with persistent asthma using a randomised double-blind, placebo-controlled, double-dummy, five-period crossover design. All patients exhibited a provocative concentration leading to a 20% decrease in forced expiratory volume in 1 s (PC(20)) methacholine <8 mg x mL(-1) and a PC(20) adenosine <60 mg x mL(-1). Primary outcome was 24-h serum cortisol suppression after 7 days. Secondary outcomes were changes in PC(20) methacholine and adenosine after 9 days. FP 500 microg x day(-1) and 1,000 microg x day(-1) significantly suppressed cortisol secretion versus placebo by -46.2 (95% confidence interval (CI) -83.8- -8.5) nmol x L(-1) and by -76.1 (95% CI -112.9- -39.3) nmol x L(-1), respectively. Neither dose of CIC (320 nor 640 microg x day(-1)) had a significant suppressive effect (-28.2 (95% CI -65.5-9.2) nmol x L(-1) and -37.3 (95% CI -74.7-0.0) nmol x L(-1), respectively). Differences between FP 1,000 microg x day(-1) and both CIC treatments were statistically significant (CIC 320 microg x day(-1): -48.0 (95% CI -84.8- -11.1) nmol x L(-1); CIC 640 microg x day(-1): -38.8 (95% CI -75.7- -1.9) nmol x L(-1)). Compared with placebo, the increase in PC(20) adenosine after the four treatments was small, but significant. Greater improvements in PC(20) adenosine were seen with FP 500 microg x day(-1) (1.8 (95% CI 1.0-2.6) doubling concentrations) compared with CIC 320 microg x day(-1) (0.9 (95% CI 0.1-1.7) doubling concentrations). No significant difference was seen between CIC 640 microg x day(-1) and FP 1,000 microg x day(-1). For a similar decrease in hyperresponsiveness, cortisol secretion was suppressed significantly with moderate-to-high doses of fluticasone propionate, but not with ciclesonide.

Topics: Adenosine; Adolescent; Adult; Aged; Albuterol; Analysis of Variance; Androstadienes; Anti-Allergic Agents; Area Under Curve; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Least-Squares Analysis; Male; Methacholine Chloride; Middle Aged; Placebos; Pregnenediones; Salmeterol Xinafoate; Spirometry; Treatment Outcome

Oral corticosteroids effectively treat asthma exacerbations but are associated with well-described side effects.. This study compared the efficacy and safety of a high dose of an inhaled corticosteroid with oral prednisolone in patients with worsening of their asthma after medication withdrawal.. Patients tapered off their inhaled corticosteroids until they reached predefined criteria of "worsening asthma". Randomized patients (n=130) were treated double blind with either ciclesonide 800mug twice daily (starting with 800mug hourly for 3h after randomization) or prednisolone 40mg once daily for 2 weeks. Spirometry, daily asthma symptoms, morning and evening peak expiratory flow and blood parameters were assessed in all, methacholine challenge and inflammatory measures were determined in induced sputum in a subset of patients.. Ciclesonide was as effective as prednisolone in improving forced expiratory flow in 1s, morning peak expiratory flow and symptoms, the latter improving more rapidly with ciclesonide. No differences were found in methacholine responsiveness or inflammatory measures in sputum or blood. Ciclesonide caused significantly less reduction in morning plasma cortisol levels (p<0.0001).. This study shows that inhaled ciclesonide (800mug twice daily) has comparable efficacy to oral prednisolone (40mg once daily) to regain asthma control in patients with asthma worsening. The more rapid onset and smaller effect on cortisol suppression suggest a better safety profile of ciclesonide.

Topics: Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisolone; Pregnenediones; Sputum

In asthma small airways inflammation often persists despite inhaled corticosteroids therapy.. To discuss the effects of ciclesonide, a newer inhaled corticosteroid on small airways inflammation and the reliability of some biomarkers of small airways inflammation in asthma.. Evaluation of a study assessing the short-term effects of ciclesonide on small airways inflammation in patients with mild to moderate asthma.. Ciclesonide could have beneficial effects on small airways inflammation and some of the outcome measures used as efficacy endpoints could represent possible biomarkers of small airways involvement in obstructive chronic respiratory diseases.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Humans; Inflammation Mediators; Pilot Projects; Pregnenediones; Pulmonary Alveoli

Inhaled corticosteroids (ICS) are recommended as first-line treatment for adults and children with persistent asthma. The Global Initiative for Asthma recommends that patients taking medium- or high-dose ICS delivered by metered-dose inhalers (MDIs) should use a spacer device.. This randomized, open-label, 12-week, non-inferiority study compared the efficacy and safety of ciclesonide 160microg once daily delivered via hydrofluoroalkane-MDI alone (CIC160) or with a spacer (either an AeroChamber Plus [CIC160P] or an AeroChamber MAX [CIC160M]) in patients with persistent asthma. The primary efficacy variable was change in forced expiratory volume in 1s (FEV(1)) from baseline to study end.. Significant improvements in FEV(1) were observed from baseline to study end in each treatment group; least squares mean change from baseline ranged between 0.32 and 0.34L in the per-protocol (PP) analysis and similar results were observed for the intention-to-treat (ITT) analysis (p<0.0001 for all). Non-inferiority of CIC160P and CIC160M to CIC160 was observed for both PP and ITT populations (p<0.0001 [one-sided]). In all groups, daily asthma symptom scores were reduced to 0 and significant reductions were observed in rescue medication use at study end (p<0.0001 versus baseline for all). Ciclesonide was well tolerated in all groups and no cases of oral candidiasis were reported. Morning serum cortisol levels significantly increased in all groups from baseline to study end (p< or =0.0389), with no significant between-treatment differences.. In patients with persistent asthma, ciclesonide was shown to have similar efficacy and tolerability when administered via MDI alone or with a spacer.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Pregnenediones; Treatment Outcome; Young Adult

Inhaled corticosteroids (ICS) are recommended first-line therapy for the treatment of persistent asthma. However, reports from observational studies have suggested that the use of ICS may be associated with systemic adverse events, such as glaucoma and cataract (opacity of the lens) formation.. To compare two ICS over 1 year regarding the formation/progression of lenticular opacities in patients with asthma.. Adults (>or=18 years of age) with moderate-to-severe asthma were randomized to ciclesonide 640 micro g/day (n = 785) or beclomethasone dipropionate 640 micro g/day (n = 783) in a multinational, double-blind, active-controlled, parallel-group study. The primary endpoint was the occurrence of a positive Class I grading shift (increase [worsening] in Lens Opacities Classification System [LOCS] III score of >or= 0.5 for nuclear opalescence, >or= 0.8 for cortical opacification, or >or= 0.5 for posterior subcapsular opacification, or cataract surgery) in either eye at any visit over the 12-month, double-blind treatment period.. Mean changes (+/- standard error) in nuclear opalescence and cortical and posterior subcapsular opacification were small and similar between groups (ciclesonide 640 micro g/day: 0.10 +/- 0.02, 0.07 +/- 0.02 and 0.04 +/- 0.01, respectively; beclomethasone dipropionate 640 micro g/day: 0.11 +/- 0.02, 0.09 +/- 0.02 and 0.03 +/- 0.01, respectively). Class I shifts were observed in 34.3% versus 36.8% of ciclesonide-treated and beclomethasone dipropionate-treated patients, respectively. Ciclesonide 640 micro g/day was non-inferior to beclomethasone dipropionate 640 micro g/day regarding Class I shifts (risk ratio of ciclesonide to beclomethasone dipropionate, 0.940 [95% confidence interval, 0.820-1.077]); the 95% confidence interval upper bound was lower than the pre-specified non-inferiority bound of 1.333 (p < 0.0001), thereby excluding the possibility of higher risk ratio values.. Mean changes in LOCS III scores were very small in both groups. Treatment with ciclesonide 640 micro g/day or beclomethasone dipropionate 640 micro g/day for 1 year has a minimal impact on lenticular opacities development and/or progression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Asthma; Beclomethasone; Cataract; Double-Blind Method; Female; Glucocorticoids; Humans; Lens, Crystalline; Male; Middle Aged; Pregnenediones; Young Adult

To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma.. This randomized, open-label, parallel-group study enrolled patients aged 12-75 years with a 6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500-1000 microg/day or equivalent at a stable dose for 4 weeks and have a forced expiratory volume in 1s (FEV 1) 80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 80% of predicted; reversibility of Delta FEV 1 12% after 200-400 microg salbutamol; and 1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 microg (ex-actuator) or twice-daily FP 330 microg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded.. 528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean+/-standard error of the mean for the treatment difference was -13+/-29 (95% confidence interval [CI]: -70, 44) in the ITT analysis and -27+/-34 (95% CI: -93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide (p=0.0023).. Ciclesonide 320 microg and FP 330 microg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Quality of Life; Recurrence; Treatment Outcome

The allergen-induced release of CCL17/thymus and activation-regulated chemokine (TARC) may be crucial in asthmatic airway inflammation by recruitment of Th2 cells. In addition, it might lead to aberrant Th2 cell activity through impairment of beta2-adrenergic receptor (beta2-AR) control. We questioned how chemokine patterns change upon allergen challenge and whether treatment with the inhaled steroid ciclesonide can reduce chemokine release and subsequently prevent allergen-induced changes in Th2 cell regulation and migration.. Asthma patients were double-blindly treated with placebo or 80 microg ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of beta2-agonist fenoterol over T cell migration and alpha-CD3/alpha-CD28-induced cytokine production.. Treatment with 80 microg ciclesonide significantly diminished the late asthmatic response. The late asthmatic response was associated with increased sputum levels of CCL17 and CCL4 (but none of the other chemokines measured) and loss of beta2-AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered beta2-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and alpha-CD3/alpha-CD28-induced cytokine production.. Our data support the hypothesis that CCL17 is involved in allergen-induced dysregulation of Th2 cell migration and cytokine production. Ciclesonide treatment inhibits T cell migration and cytokine production upon allergen inhalation, which is regulated independently from reducing CCL17 release, but may contribute to beneficial effects of ciclesonide on Th2-mediated airway inflammation.

Topics: Adolescent; Adult; Allergens; Anti-Asthmatic Agents; Arrestins; Asthma; beta-Arrestins; Cell Movement; Chemokine CCL17; Chemokine CCL4; Cytokines; Double-Blind Method; Female; Fenoterol; Humans; Male; Middle Aged; Pregnenediones; Receptors, Adrenergic, beta-2; Sputum; T-Lymphocyte Subsets; Th2 Cells

To assess the effects of the new inhaled corticosteroid ciclesonide on growth in children with asthma.. We performed a multicenter, randomized, double-blind, placebo-controlled study to assess the effects of inhaled ciclesonide on growth in children with mild, persistent asthma. After a 6-month run-in period, 661 prepubertal children who were aged 5.0 to 8.5 years were randomly assigned to once-daily morning treatment for 1 year with ciclesonide 40 or 160 microg (ex-actuator) or placebo, followed by a 2-month follow-up period. The primary end point was the linear growth velocity (linear regression estimate) over the double-blind treatment period. Growth was recorded as the median of 4 stadiometer measurements. Adverse events and 10-hour overnight and 24-hour urinary free cortisol levels were also assessed.. Mean linear growth velocity during run-in was comparable between groups: 160 microg, 6.20 cm/year; 40 microg, 6.59 cm/year; placebo, 6.49 cm/year. Mean differences from placebo (5.75 cm/year) in growth velocity over the double-blind treatment period were -0.02 cm/year for ciclesonide 40 microg and -0.15 cm/year for ciclesonide 160 microg. Both ciclesonide treatments were noninferior to placebo with respect to growth velocity. The overall incidence of adverse events was comparable between groups, and no significant changes in 10-hour overnight or 24-hour urinary free cortisol levels were noted between groups during the double-blind treatment period.. Ciclesonide demonstrated no detectable effect on childhood growth velocity, even at the highest dosage, which may ease concerns about systemic adverse events.

Topics: Administration, Inhalation; Asthma; Body Height; Child; Child Development; Child, Preschool; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Growth; Humans; Male; Multivariate Analysis; Pregnenediones; Reference Values; Risk Assessment; Severity of Illness Index; Spirometry; Treatment Outcome

The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined.. Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed.. Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time.. These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs.. clinicaltrial.gov; Identifier: NCT00525772.

Topics: Adolescent; Adult; Anti-Allergic Agents; Asthma; Bronchoconstriction; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Pregnenediones; Spirometry; Sputum

Demonstrating clinical benefit of higher doses of inhaled corticosteroids in asthma is frequently problematic owing to their relatively flat dose-response curve in this condition. In this study we compared the efficacy and safety of a fourfold difference in the dose of ciclesonide-ciclesonide 320 microg twice daily (CIC640) versus ciclesonide 160 microg once daily (CIC160)-in patients with severe persistent asthma.. Patients with bronchial asthma (6 months) were included in this randomized, double-blind study. After receiving fluticasone propionate 250 microg twice daily during run-in, patients were randomized to CIC160 (n=339) or CIC640 (n=341) for 12 weeks. Primary endpoints were time to first asthma exacerbation and forced expiratory volume in 1s (FEV(1)). Secondary endpoints included other lung function variables, asthma symptom scores and rescue medication use (RMU).. Asthma exacerbations occurred in 12.7% of patients receiving CIC160 and 6.7% receiving CIC640. CIC640 was superior for time to first exacerbation (p=0.0050, one-sided). FEV(1) increased significantly with CIC160 and CIC640 (least squares mean+/-SE of mean: 269+/-31 and 332+/-31 mL, respectively; p<0.0001), with no significant difference between groups. Change in % predicted FEV(1) and morning peak expiratory flow (PEF) were significantly higher with CIC640 (p<0.05). Asthma symptom score sums and RMU decreased in both groups; CIC640 was statistically superior (p=0.0108 and 0.0005, respectively). No unexpected adverse events were reported in either group and the majority of the events reported were mild or moderate in intensity. No significant changes in serum cortisol were observed from the baseline to the study end. Small decreases in creatinine-adjusted 24h urine cortisol levels from baseline were seen in both the treatment groups, which, due to the large patient numbers, were statistically significant (p<0.05); however, no dose-response effect was seen and the difference between groups was not significant (p=0.7892).. CIC640 was superior to CIC160 for time to first exacerbation, % predicted FEV1, morning PEF, asthma symptom score sum and RMU in patients with severe asthma; both doses had similar tolerability profiles and no significant changes in serum cortisol were seen in either treatment group.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Candidiasis; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Pregnenediones; Quality of Life; Vital Capacity

Ciclesonide is delivered as a small-particle inhaled corticosteroid and improves lung function and airway hyperresponsiveness. The objective of the present study was to assess whether ciclesonide can specifically improve small airway function in asthma. A total of 16 mild-to-moderate asthma patients (seven males; median (range) age 39 (19-56) yrs and forced expiratory volume in one second (FEV(1)) 89 (62-120)% predicted) were randomised to 5 weeks' treatment with placebo or 320 mug ciclesonide once daily. The following small airway parameters were assessed: mean forced expiratory flow between 25 and 75% of forced vital capacity (FVC), percentage fall in FVC at provocative dose of adenosine-5'-monophosphate and of methacholine (MCh) causing a 20% fall in FEV(1), expiratory lung volume on computed tomography (CT) scan after MCh challenge, single-breath nitrogen closing volume and alveolar exhaled nitric oxide (eNO). Seven subjects received placebo and nine received ciclesonide. Both alveolar eNO and CT measurements of expiratory lung volume after MCh challenge decreased significantly with ciclesonide (median (range) decrease 4.4 (54.8-1.4) ppb and 59 (1,569- -117) mL, respectively), and compared with placebo (-0.4 (7.3- -3.4) ppb and -121 (20- -236) mL respectively). Ciclesonide did not significantly improve other small airways parameters. Inflammation and patency of small airways, reflected by alveolar exhaled nitric oxide and air trapping on computed tomography scan, both improve with ciclesonide even in this small number of patients. This indicates that ciclesonide exerts anti-inflammatory effects on small airways.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchi; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Middle Aged; Pilot Projects; Pregnenediones; Vital Capacity

Ciclesonide is a novel inhaled corticosteroid for the treatment of asthma, and it is important to measure the onset of effect of this therapy on airway hyperresponsiveness (AHR), exhaled nitric oxide (NO), and levels of eosinophils in induced sputum.. In a randomized, double-blind, crossover study, 21 patients with mild asthma inhaled ciclesonide 320 microg (ex-actuator) qd, ciclesonide 640 microg (ex-actuator) bid, and placebo for 7 days. Exhaled NO and AHR to adenosine monophosphate (AMP), measured as the provocative concentration of AMP producing a 20% reduction in FEV1 (PC20FEV1), were assessed after inhalation on days 1, 3 and 7. Eosinophil levels in induced sputum were also measured.. Ciclesonide 320 microg qd and 640 microg bid produced significantly greater improvements in PC20FEV1 compared with placebo on day 1 (within 2.5 h), and on days 3 and 7 (all p < 0.0001). On day 3, both ciclesonide doses significantly reduced exhaled NO levels by - 17.7 parts per billion (p < 0.0001) and - 15.4 parts per billion (p < 0.003) vs placebo, respectively. Significant reductions were maintained during the study with both ciclesonide doses (p < 0.01). A nonsignificant trend towards a decrease in eosinophil cell numbers was observed after 7 days of ciclesonide treatment, especially in patients receiving the higher dose.. A single dose of ciclesonide decreased AHR to AMP and exhaled NO within 3 h, while FEV, improved at 3 days and 7 days.

Topics: Administration, Inhalation; Adult; Anti-Allergic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Humans; Leukocyte Count; Male; Nitric Oxide; Pregnenediones; Sputum

Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma.. A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study.. Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels.. Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pregnenediones; Treatment Outcome; Vital Capacity

To compare the effects of once-daily ciclesonide and twice-daily fluticasone propionate in patients with moderate persistent asthma.. Patients aged 12-75 years with moderate bronchial asthma entered a 1-4 week run-in period. For inclusion into the 12-week, randomized, open-label treatment period, patients had to have a forced expiratory volume in 1s (FEV1) of either 60-80% of predicted or 80% of predicted and a defined use of rescue medication and asthma symptoms, depending on previous treatment. Patients received ciclesonide 320 microg once daily (ex-actuator) or fluticasone propionate 200 microg twice daily. Primary efficacy endpoint was change from baseline in FEV1.. In total, 474 patients were randomized. FEV1 increased significantly from baseline with ciclesonide and fluticasone propionate in the intention-to-treat (ITT) and per-protocol (PP) analyses (all p < 0.0001). Treatment difference was -31 mL (95% confidence interval [CI]: -121, 59) in the PP analysis, demonstrating non-inferiority of ciclesonide. Similar findings were seen for other measures of lung function. In the ITT population, asthma symptom scores and rescue medication use decreased with both treatments (all p < 0.0001). Improvement in health-related quality of life (HRQoL) from baseline was significantly greater with ciclesonide than fluticasone (p = 0.005; one-sided). There were no cases of oral candidiasis in patients receiving ciclesonide and nine cases (3.8%) in those receiving fluticasone propionate (p = 0.002; one-sided).. Treatment with once-daily ciclesonide and twice-daily fluticasone propionate resulted in similar improvements in lung function in patients with moderate persistent asthma. Ciclesonide showed significant improvements in oral candidiasis and HRQoL over fluticasone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests

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.. A placebo-controlled, multicentre, randomized, 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.. 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.. 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.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Least-Squares Analysis; Male; Pregnenediones; Spirometry; Vital Capacity

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.. This was a multicentre, randomized, 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 randomly 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.. 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.. 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.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Pregnenediones

The aim of the study was to investigate the efficacy and safety of ciclesonide compared with budesonide in adolescents with severe asthma.. In this randomized, double-blind, double-dummy, parallel-group study, patients aged 12-17 years with severe asthma were treated with budesonide 400 microg once daily (QD) in a 2-week run-in period. At randomization, eligible patients were assigned 2:1 to ciclesonide 320 microg QD (ex-actuator) or budesonide 800 microg QD (metered dose), respectively, in the evening. Forced expiratory volume in 1s (FEV(1)) was the primary variable. Patients recorded asthma symptom score and rescue medication use in diaries. Safety assessments included adverse events (AEs) and 24-h urine cortisol.. Four hundred and three patients were randomized. Ciclesonide 320 microg QD and budesonide 800 microg QD significantly increased FEV(1) (least-squares mean: 505 and 536 mL, respectively; both p<0.0001 versus baseline) in the intention-to-treat (ITT) population. Lower limits of the 95% confidence intervals (ITT: -138 mL; per-protocol: -122 mL) were above the non-inferiority limit (-150 mL). Median percentage of days without asthma symptoms and without rescue medication use was 84% with ciclesonide and 85% with budesonide. AEs were unremarkable, with no cases of confirmed candidiasis. Median creatinine-adjusted urine cortisol significantly decreased with budesonide treatment (15.9-13.7 nmol cortisol/mmol creatinine; p=0.0086 versus baseline), but not with ciclesonide (p=0.1125).. Ciclesonide 320 microg QD showed similar efficacy to budesonide 800 microg QD in adolescents with severe asthma. Ciclesonide was well tolerated and, unlike budesonide, had no effect on urine cortisol levels.. EudraCT No.: 2004-001233-41.

Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Pregnenediones; Quality of Life; Treatment Outcome; Vital Capacity

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.

Topics: Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Humans; Male; Pregnenediones; Respiratory Function Tests; Treatment Outcome

To compare a step-down approach in well-controlled asthma patients, as recommended by treatment guidelines, from fluticasone propionate 250 microg twice daily (FP250 BID), or equivalent, to ciclesonide 160 microg once daily (CIC160 OD) with continued FP250 BID treatment.. Patients with well-controlled asthma prior to study entry were included in two identical, randomized, double-blind, double-dummy, parallel-group studies. After a 2-week run-in period with FP250 BID, patients were randomized to CIC160 OD (n = 58) or FP250 BID (n = 53) for 12 weeks. Primary endpoints were percentage of days with asthma control, asthma symptom-free days, rescue medication-free days and nocturnal awakening-free days. Secondary endpoints included lung function variables, asthma symptom scores, rescue medication use and asthma exacerbations. Safety variables were also recorded.. Patients had >or= 97% of days with asthma control, 98% asthma symptom-free days and 100% of days free from rescue medication use and nocturnal awakenings in both treatment groups (median values). There were no significant between-treatment differences for any of the primary or secondary efficacy variables. Overall, 42 treatment-emergent adverse events (TEAEs) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group. There were no clinically relevant changes from baseline in the safety variables in either treatment group.. Patients well controlled on FP250 BID, or equivalent, who were stepped down to CIC160 OD, maintained similar asthma control compared with patients who received continued treatment standardized to FP250 BID.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Pregnenediones; Treatment Outcome

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 randomized to once-daily ciclesonide 80 micro g (n = 278) or 160 micro g (n = 271), or twice daily fluticasone propionate 88 micro 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 micro g or 160 micro g showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 micro g in persistent asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests

Coexisting asthma and allergic rhinitis (AR) are often treated with both intranasal and inhaled corticosteroids. This study investigated whether intranasal ciclesonide 200 microg once daily has an additional effect on cortisol suppression when coadministered with inhaled hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP). Adult patients (n = 150) with perennial AR received HFA-BDP 320 microg twice daily and placebo once daily during a run-in period. Patients were then randomized to ciclesonide or placebo and HFA-BDP (43 days). A single 2-mg dose of dexamethasone was administered on the last treatment day. Plasma cortisol decreased by 67.8 microg x h/dL (p < 0.001) during the run-in period. When ciclesonide was added, the change in mean plasma cortisol was similar for ciclesonide and placebo (8.5 microg x h/dL and 1.0 microg x h/dL, respectively). Dexamethasone decreased mean plasma cortisol (p < 0.001), demonstrating that further cortisol suppression was possible. This study suggests that intranasal ciclesonide can be used with an inhaled corticosteroid without increased cortisol suppression.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Adult; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Patient Compliance; Pituitary-Adrenal System; Pregnenediones; Rhinitis, Allergic, Perennial

Experience with ciclesonide in patients with mild persistent bronchial asthma The study aimed to monitor the effectiveness and safety of the treatment with ciclesonide, administered once a day in a 160 microg dose, over a 3-month period, to a group of 100 patients diagnosed with mild persistent bronchial asthma with deterioration of problems after exercise. The results of the study prove significant positive effects of the preparation used. A significant improvement of FEV1 and PEF values was observed, as well as a statistically significant remission of both day and nocturnal symptoms of the disease, a significantly lower consumption of short-acting beta2-sympathomimetics, and an improvement of all evaluated data relating to the quality of life of the asthmatic patients. No adverse effects were registered.

Topics: Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Humans; Pregnenediones

Inhaled corticosteroids are the mainstay of therapy in asthma, but local and systemic side effects and adherence remain a concern. Ciclesonide is an inhaled corticosteroid with on-site lung activation that provides potent anti-inflammatory activity and has been shown to have a good safety profile, even at high doses.. The aim of this study was to compare the efficacy and safety of once-daily ciclesonide versus twice-daily fluticasone propionate at comparable daily doses in patients with asthma.. In this multicenter, randomized, double-blind, double-dummy, parallel group study, 529 patients were randomized to ciclesonide 160 microg once daily or fluticasone propionate 88 microg twice daily for 12 weeks. The primary endpoint was change in lung function.. Both ciclesonide and fluticasone propionate significantly improved forced expiratory volume in 1s, forced vital capacity, and morning peak expiratory flow compared with baseline (p<0.0001 for all variables). Both medications reduced asthma symptoms and rescue medication use within the first 24 h. At the tested dose, both medications were equally safe and well tolerated.. Ciclesonide 160 microg once daily was as effective as fluticasone propionate 88 microg twice daily in improving lung function and asthma symptoms, and in reducing rescue medication use in patients with asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests; Vital Capacity

To evaluate whether the inflammatory process and bronchial constriction associated with asthma influence the pulmonary distribution and airway penetration of inhaled ciclesonide by investigating the pharmacokinetics of ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC) in patients with asthma and matched healthy subjects.. 12 patients with asthma (8 males, 4 females) and 12 healthy subjects matched for age, sex, height, and weight received a single inhaled dose of 1,280 microg (ex-actuator, equivalent to 1,600 microg ex-valve) ciclesonide by metered-dose inhaler in a parallel-group study. Timed blood samples were collected for measurement of serum concentrations of des-CIC and ciclesonide by liquid chromatography with tandem mass spectrometry.. There were no differences in the pharmacokinetics of des-CIC between healthy subjects and patients with asthma. Ratio analysis of the primary variable, the area under the concentration-time curve from time 0 to infinity (AUC(0 - inf)) showed equivalence for des-CIC in healthy subjects and patients with asthma, with a ratio of 1.003 (90% confidence interval between 0.815 and 1.234). The mean terminal half-life (t1/2) for des-CIC was also similar in patients with asthma (3.15 hours) and healthy subjects (3.33 hours). Furthermore, the pharmacokinetic parameter estimates for ciclesonide were comparable between the study groups.. After administration of a single dose of ciclesonide, the pharmacokinetic parameter estimates for des-CIC were equivalent between patients with mild-to-moderate asthma and healthy subjects, suggesting that there is comparable lung deposition and activation of ciclesonide in the 2 populations.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Case-Control Studies; Dose-Response Relationship, Drug; Female; Half-Life; Headache; Humans; Male; Middle Aged; Pregnenediones

The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma.. Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint.. In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups.. Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Vital Capacity

Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Asthma; Breath Tests; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Pregnenediones; Treatment Outcome

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.. Overall, 1031 children age 4 to 11 years were randomized 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 designed 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.. 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.. In this integrated analysis, ciclesonide was effective and well tolerated in children with persistent asthma.

Topics: Adrenal Cortex Hormones; Albuterol; Asthma; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Forced Expiratory Volume; Humans; Hydrocortisone; Metered Dose Inhalers; Pregnenediones; Quality of Life; Severity of Illness Index; Treatment Outcome

Ciclesonide exhibits clinical efficacy at 160 microg (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 microg once daily in the morning exhibited significant anti-inflammatory effects.. Seventeen patients with mild persistent asthma (FEV(1) 3.35 l) were recruited into a double-blind placebo-controlled randomized crossover study. Measurements were made after ciclesonide and placebo treatment as well as after run-in and washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup).. The mean (SEM) AMP bronchial challenge PC(20) following ciclesonide (140 (63) mg/ml) was significantly (P < 0.001) increased compared with placebo (17 (8) mg/ml), run-in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to an eightfold (CI: 5.3-12.0) for ciclesonide vs placebo. Likewise, there were significant improvements in exhaled NO levels and a significant reduction in induced sputum eosinophil cell counts.. We have shown that inhaled ciclesonide given at 160 microg once daily in the morning exhibits significant anti-inflammatory effects that are in keeping with the previously described clinical effects.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Anti-Inflammatory Agents; Asthma; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pregnenediones; Severity of Illness Index; Time Factors; Treatment Outcome

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.. A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study.. Adult and adolescent patients (> or = 12 years old; n = 141) with severe, persistent, oral steroid (prednisone)-dependent asthma.. Patients were randomized 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.. 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.. Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe, persistent asthma, while maintaining asthma control.

Topics: Administration, Oral; Adolescent; Adult; Aged; Asthma; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Prednisone; Pregnenediones; Severity of Illness Index; Treatment Outcome

Ciclesonide is an inhaled corticosteroid that provides safe and effective control of persistent asthma. Ciclesonide is administered as an aerosol solution in a metered-dose inhaler, using hydrofluoroalkane-134a as a propellant. It is activated in the lung to form its only active metabolite, desisobutyryl-ciclesonide (des-CIC). A spacer may be used in combination with the hydrofluoroalkane metered-dose inhaler (HFA-MDI) to maintain inhaled corticosteroid delivery to the lung in patients with poor inhalation technique.. To determine if the pharmacokinetics of des-CIC and ciclesonide are altered when a spacer is used for ciclesonide inhalation.. A randomised, open-label, 2-period crossover, single-center pharmacokinetic study was conducted in 30 patients with asthma (forced expiratory volume in 1 second > or = 70% predicted). A single dose of ciclesonide (320 microg ex-actuator; equivalent to 400 microg ex-valve) was administered via the HFA-MDI with and without an AeroChamber Plus spacer (Trudell Medical International, London, ON, Canada). Serum concentrations of ciclesonide and des-CIC were measured before inhalation and at various intervals until 14 hours after treatment using high-performance liquid chromatography with tandem mass spectrometric detection.. The pharmacokinetic properties of the active metabolite, des-CIC, were equivalent after inhalation of ciclesonide with and without the AeroChamber Plus spacer. Point estimates and 90% confidence intervals (CIs) for the ratio of des-CIC pharmacokinetic properties in the presence or absence of a spacer were within the conventional bioequivalence range of 0.80-1.25 (area under the serum concentration time curve from time zero to infinity 0.96 [0.85, 1.07]; peak serum concentration 1.05 [0.94, 1.18]; elimination half-life 1.04 [0.92, 1.18]). Furthermore, there was no relevant difference in the point estimate and 90% CI of the difference of the time to reach peak serum concentration of des-CIC with or without a spacer.. The AeroChamber Plus spacer did not influence the pharmacokinetics of the pharmacologically active des-CIC. Thus, systemic exposure to the active metabolite is similar when ciclesonide is inhaled with or without a spacer. Furthermore, these results are indicative of comparable lung deposition of ciclesonide in both the presence and absence of a spacer.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Area Under Curve; Asthma; Biotransformation; Chromatography, High Pressure Liquid; Cross-Over Studies; Female; Half-Life; Humans; Male; Mass Spectrometry; Middle Aged; Nebulizers and Vaporizers; Pregnenediones

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.. This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma.. This 12-week, randomized 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 randomly assigned to receive inhaled ciclesonide 80 or 320 microg QD (morning) or budesonide 200 microg BID for 12 weeks. Efficacy and tolerability assessments 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 standard 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.. Five hundred fifty-four patients were randomized (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

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Child; Double-Blind Method; Female; Glucocorticoids; Humans; Hydrocortisone; International Cooperation; Male; Middle Aged; Pregnenediones; Respiratory Function Tests

Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Pregnenediones; Respiratory Function Tests

The predominance of T-helper type 2 (Th2) lymphocytes is thought to underlie the pathogenesis of asthma. Allergen inhalation challenge in atopic asthmatic subjects is associated with decreased interferon-gamma (IFN-gamma) positive CD4+ and CD8+ lymphocytes in peripheral blood and induced sputum.. This study examined the effects of an inhaled corticosteroid on these previously described allergen-induced changes in circulating Th1 and Th2 lymphocytes.. Subjects were randomized to 7 days of placebo, 40 or 80 micro g ciclesonide in a crossover study. Airway responses and peripheral blood were measured before and after treatment, and 24 h after allergen challenge.. Ciclesonide 40 and 80 micro g significantly attenuated the late response and sputum eosinophils at 8 h post-allergen (P<0.05). Circulating IFN-gamma positive CD4+ lymphocytes decreased after allergen challenge with placebo (P<0.05), and this was inhibited by 40 micro g ciclesonide treatment (P<0.05). There was no effect of allergen inhalation or ciclesonide on IL-4-positive CD4+ lymphocytes or IFN-gamma and IL-4-positive CD8(high) lymphocytes. The allergen-induced change of IFN-gamma/IL-4 ratio on CD4+ cells correlated with the allergen-induced change of peripheral blood eosinophils.. The results of this study suggest that attenuation of allergen-induced airway responses by ciclesonide may be mediated through regulation of IFN-gamma-positive CD4+ cells.

Topics: Administration, Inhalation; Adult; Allergens; Analysis of Variance; Asthma; Biomarkers; Bronchial Provocation Tests; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Eosinophils; Female; Flow Cytometry; Glucocorticoids; Humans; Hypersensitivity; Interferon-gamma; Interleukin-4; Lymphocyte Count; Male; Methacholine Chloride; Pregnenediones; Sputum

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, randomized, 2-treatment, 2-sequence study design. The oropharynx was washed out immediately and at 15, 30, 45, and 60 minutes after inhalation. Samples were analyzed for ciclesonide, des-CIC, and FP using liquid chromatography with tandem 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 samples. 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.

Topics: Administration, Inhalation; Adult; Androstadienes; Area Under Curve; Asthma; Chromatography, Liquid; Cough; Drug Administration Schedule; Ethanol; Female; Fluticasone; Humans; Male; Mass Spectrometry; Metered Dose Inhalers; Oropharynx; Pregnenediones; Solutions; Therapeutic Irrigation; Time Factors

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, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma.. After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy.. Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis.. Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones; Salvage Therapy; Spirometry; Treatment Outcome

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.. 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.. Fourteen patients with moderate persistent asthma (mean FEV(1), 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, 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 randomized 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.. 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.. 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.

Topics: Administration, Inhalation; Androstadienes; Asthma; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Corticotropin-Releasing Hormone; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Nitric Oxide; Peak Expiratory Flow Rate; Pregnenediones; Quality of Life; Spirometry

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.. We sought to determine the effects of clinically effective doses of the novel inhaled corticosteroid ciclesonide on lower-leg growth rate and hypothalamic-pituitary-adrenal axis function in children with asthma.. 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 randomized 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.. 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.. 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.

Topics: Administration, Inhalation; Asthma; Biometry; Body Height; Child; Cross-Over Studies; Double-Blind Method; Female; Humans; Hydrocortisone; Leg; Male; Pregnenediones

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.. 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.. This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized 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.. 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 candidiasis 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.. 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.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Patient Compliance; Pituitary-Adrenal System; Pregnenediones

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 randomized, 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 samples 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.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adolescent; Adult; Androstadienes; Area Under Curve; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocortisone; Lung; Male; Middle Aged; Pregnenediones; Spirometry; Treatment Outcome

The efficacy and safety of ciclesonide was assessed in this randomized, placebo-controlled study in patients with persistent asthma (randomized n=360) maintained on low to moderate doses of inhaled corticosteroids. Patients were randomized 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.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Asthma; Canada; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones; United Kingdom; Vital Capacity

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.. 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.. Twenty-one nonsmokers with mild atopic asthma completed a multicenter, randomized, 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.. 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).. 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.

Topics: Adult; Allergens; Asthma; Cross-Over Studies; Eosinophil Cationic Protein; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones

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.. Adult patients (n = 60; > or = 18 years of age) with moderate-to-severe asthma were randomized 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].. 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.. Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Pregnenediones

Inhaled corticosteroids are recommended as first-line therapy for persistent asthma.. We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma.. An integrated analysis of 2 identical, multicenter, double-blind, randomized, 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 randomized to ciclesonide 80 microg (CIC80), 160 microg (CIC160), or 320 microg (CIC320), once daily (exactuator doses) in the morning or placebo for 12 weeks.. 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.. In this integrated analysis, ciclesonide once daily administered in the morning is effective and well tolerated.

Topics: Adult; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Pregnenediones

The efficacy of ciclesonide 160 mug QD (given either in the morning or evening) was compared with budesonide 200 mug BID in adults with stable asthma that was pretreated with inhaled corticosteroids.. This was a randomized, 3-arm, parallel-group study comparing ciclesonide (given in a double-blind, double-dummy regimen) with open-label budesonide. After 2 to 2.5 weeks, during which patients were treated with budesonide 200 microg BID, patients (n = 405) were randomly assigned to receive ciclesonide 160 microg QD AM or 160 microg QD pm, or budesonide 200 microg BID (all administered by metered-dose inhaler) for 12 weeks. All patients received 2 puffs of medication (or placebo) in the morning and evening. The primary efficacy variable was the difference in spirometric forced expiratory volume in 1 second (FEV(1) in liters) from randomization to study end. Secondary efficacy end points were forced vital capacity, peak expiratory flow by spirometry, and diary assessments of peak expiratory flow, asthma symptoms, and rescue medication use. Adverse events were assessed by patient report, investigator observation, physical examination, and laboratory testing; events were classified as mild, moderate, or severe.. Baseline demographic characteristics with regard to sex, age, weight, smoking status, baseline medication use, and FEV(1) were balanced among the treatment groups. Over the course of treatment, both ciclesonide and budesonide maintained FEV(1) compared with baseline. Both ciclesonide regimens were as effective as budesonide 200 microg BID in maintaining FEV(1) during the treatment period versus baseline (ciclesonide 160 microg QD am: 95% CI, -0.120 to 0.045 vs budesonide; P = NS; ciclesonide 160 microg QD pm: 95% CI, -0.061 to 0.105 vs budesonide; P = NS). Ciclesonide 160 microg QD (morning or evening) was comparable with budesonide 200 microg BID for maintaining pulmonary function, asthma symptom scores, and rescue medication use. The incidence of adverse events was not significantly different among the treatment groups, and most adverse events were not related to study medication.. In this study, ciclesonide 160 microg QDwas as effective as budesonide 200 microg BID (400 microg total daily dose) in these adults with persistent asthma. Both treatments were well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Flow Rates; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones

Ciclesonide is an inhaled corticosteroid (delivered via a hydrofluoroalkane metered-dose inhaler) that is converted to an active metabolite, desisobutyryl-ciclesonide, in the lung, thereby minimising effects on endogenous cortisol. In two 12-week, randomised studies in patients with asthma, ciclesonide 80 or 320 microg once daily was at least as effective as budesonide 400 microg/day at increasing forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline; ciclesonide 320 microg daily was significantly more effective than budesonide 400 microg once daily in one study. In a randomised, double-blind study in patients with asthma controlled with high-dosages of inhaled corticosteroids, FEV(1) and FVC decreased significantly from baseline at 12 weeks in patients receiving ciclesonide 320 microg daily or budesonide 400 microg daily; peak expiratory flow values decreased significantly only in patients receiving budesonide. Inhaled ciclesonide 80 or 320 microg daily improved asthma symptom scores and decreased the use of rescue medication by a similar, significant amount to budesonide 400 microg/day in two 12-week studies. Inhaled ciclesonide was generally well tolerated in patients with asthma. Ciclesonide did not suppress biochemical markers of adrenal function in 52-week studies. The long-term (>52 weeks) systemic effects of ciclesonide remain unknown.

Topics: Administration, Inhalation; Adult; Asthma; Budesonide; Drug Administration Schedule; Esterases; Half-Life; Humans; Injections, Intravenous; Metered Dose Inhalers; Pregnenediones; Time Factors

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.. Nineteen mild-to-moderate asthmatic patients completed the study per protocol in randomized, 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 randomized 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.. 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.. 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.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Methacholine Chloride; Middle Aged; Pregnenediones; Vital Capacity

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.. The study was designed as a double-blind placebo-controlled randomized crossover trial. Following a baseline period, patients were randomized to either of two treatment sequences (ciclesonide/placebo, placebo/ciclesonide) each of which lasted for one week and were separated by 3-5 weeks from the alternate treatment sequence. Patients received 800 micro g ciclesonide twice daily by means of a Cyclohaler. At the end of each treatment patients were subjected to an allergen challenge.. Thirteen asthmatic patients (mean FEV1 of 91% predicted) who experienced an EAR and LAR after allergen challenge participated in the study. The time-average FEV1 decreases 0-2 h (2-12 h) after allergen challenge as measure of the EAR (LAR) were significantly reduced (P < 0.05, one-sided) from 0.426 L to 0.233 L (EAR) and from 0.443 L to 0.213 L (LAR), respectively. Thus, the study results suggest that ciclesonide significantly lowered the extent of EAR and LAR compared to placebo. Ciclesonide was well tolerated and no drug-related adverse events were reported. Cortisol excretion in 24-h urine showed no significant difference between ciclesonide and placebo.. The study supports the efficacy and safety of ciclesonide.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests; Treatment Outcome

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, randomized, 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.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adult; Airway Resistance; Anti-Asthmatic Agents; Asthma; Breath Tests; Female; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Pregnenediones; Respiratory Function Tests; Sputum

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, randomized, 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.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Humans; Lung Volume Measurements; Male; Middle Aged; Pregnenediones; Spirometry; Treatment Outcome

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, randomized, 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.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adolescent; Adult; Airway Resistance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Ribonucleases; Sputum; Treatment Outcome

Topics: Administration, Inhalation; Asthma; COVID-19; Humans; Pregnenediones; Pulmonary Disease, Chronic Obstructive

Topics: Administration, Inhalation; Asthma; COVID-19; Humans; Pregnenediones; Pulmonary Disease, Chronic Obstructive

The development of more efficient drug delivery devices for ciclesonide inhalation products requires an ultrasensitive bioanalytical method to measure systematic exposure of ciclesonide (CIC) and its active metabolite desisobutyryl-ciclesonide (des-CIC) in humans.. Serum sample was extracted with 1-chlorobutane. A reversed-phase liquid chromatography coupled with atmospheric pressure photoionization-tandem mass spectrometry (LC-APPI-MS/MS) method was used for quantification of 1-500 pg/mL for both analytes in a 0.500-mL serum. The analysis time was 4.7 min/injection. CIC-d11 and des-CIC-d11 were used as the internal standards.. Calibration curves showed good linearity (r2 > 0.99) for both analytes. This novel method was precise and accurate with interassay precision and accuracy of all within 9.6% CV and ± 4.0% bias for regular QC samples. Extraction recovery was approximately 85% for both analytes. Serum samples are stable for 3 freeze-thaw cycles, 24 h at bench top, and up to 706 days at both -20 °C and -70 °C. This method was successfully used to support a pharmacokinetic (PK) comparison between the inhalation suspensions and an inhalation aerosol of ciclesonide in healthy participants. The method robustness was also supported by the good incurred sample reanalysis reproducibility.. APPI, a highly selective and sensitive ionization source, made possible for quantifying CIC and des-CIC with a lower limit of quantification (LLOQ) of 1 pg/mL in human serum by LC-MS/MS. A 10-fold sensitivity improvement from the most sensitive reported method (LLOQ, 10 pg/mL) is essential to fully characterize the PK profiles of CIC and des-CIC in support of the clinical development of the ciclesonide-related medications for patients.

Topics: Administration, Inhalation; Asthma; Chromatography, Liquid; Dimensional Measurement Accuracy; Drug Delivery Systems; Drug Elimination Routes; Glucocorticoids; Half-Life; Humans; Nebulizers and Vaporizers; Pregnenediones; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

Ciclesonide is an FDA-approved glucocorticoid (GC) used to treat asthma and allergic rhinitis. However, its effects on cancer and cancer stem cells (CSCs) are unknown. Our study focuses on investigating the inhibitory effect of ciclesonide on lung cancer and CSCs and its underlying mechanism. In this study, we showed that ciclesonide inhibits the proliferation of lung cancer cells and the growth of CSCs. Similar glucocorticoids, such as dexamethasone and prednisone, do not inhibit CSC formation. We show that ciclesonide is important for CSC formation through the Hedgehog signaling pathway. Ciclesonide reduces the protein levels of GL1, GL2, and Smoothened (SMO), and a small interfering RNA (siRNA) targeting SMO inhibits tumorsphere formation. Additionally, ciclesonide reduces the transcript and protein levels of SOX2, and an siRNA targeting SOX2 inhibits tumorsphere formation. To regulate breast CSC formation, ciclesonide regulates GL1, GL2, SMO, and SOX2. Our results unveil a novel mechanism involving Hedgehog signaling and SOX2 regulated by ciclesonide in lung CSCs, and also open up the possibility of targeting Hedgehog signaling and SOX2 to prevent lung CSC formation.

Topics: A549 Cells; Animals; Anti-Asthmatic Agents; Apoptosis; Asthma; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Hedgehog Proteins; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplastic Stem Cells; Pregnenediones; RNA, Small Interfering; Signal Transduction; SOXB1 Transcription Factors; United States; United States Food and Drug Administration

Raman spectroscopy is a powerful tool for investigating chemical composition. Coupling Raman spectroscopy with optical microscopy (Raman microspectroscopy) and optical trapping (Raman tweezers) allows microscopic length scales and, hence, femtolitre volumes to be probed. Raman microspectroscopy typically uses UV/visible excitation lasers, but many samples, including organic molecules and complex tissue samples, fluoresce strongly at these wavelengths. Here we report the development and application of dispersive Raman microspectroscopy designed around a near-infrared continuous wave 1064 nm excitation light source. We analyze microparticles (1-5 μm diameter) composed of polystyrene latex and from three real-world pressurized metered dose inhalers (pMDIs) used in the treatment of asthma: salmeterol xinafoate (Serevent), salbutamol sulfate (Salamol), and ciclesonide (Alvesco). For the first time, single particles are captured, optically levitated, and analyzed using the same 1064 nm laser, which permits a convenient nondestructive chemical analysis of the true aerosol phase. We show that particles exhibiting overwhelming fluorescence using a visible laser (514.5 nm) can be successfully analyzed with 1064 nm excitation, irrespective of sample composition and irradiation time. Spectra are acquired rapidly (1-5 min) with a wavelength resolution of 2 nm over a wide wavenumber range (500-3100 cm

Topics: Aerosols; Albuterol; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Equipment Design; Fluorescence; Humans; Metered Dose Inhalers; Optical Tweezers; Particle Size; Pregnenediones; Salmeterol Xinafoate; Spectrum Analysis, Raman

This case series intends to highlight the association between decreased linear growth velocity and adrenal suppression in patients receiving inhaled corticosteroids for asthma. A potential treatment option is also discussed. Adrenal suppression secondary to inhaled corticosteroids has previously been reported and is often underrecognized. A decrease in linear height velocity has also been associated with inhaled corticosteroids. However, a decrease in height velocity has not been shown to predict adrenal suppression.. This case series of 15 patients receiving inhaled corticosteroids for control of asthma were noted to have a decrease in linear growth velocity ultimately associated with adrenal suppression. A change in inhaled corticosteroid to ciclesonide led to recovery of adrenal function without impacting asthma control.. Chart review from a pediatric pulmonology clinic was performed. Growth parameters and laboratory studies were recorded and analyzed. A mean decrease in height standard deviation score in the year prior to diagnosis of adrenal suppression was -0.59, -0.11, and -0.18, in pre-puberty, peri-puberty, and post-puberty patients, respectively. After ciclesonide therapy was initiated, a mean change in height standard deviation score of +0.40, +0.13, and -0.13, was noted for pre-puberty, peri-puberty, and post-puberty patients, respectively. A change in growth velocity of +5.3 cm/yr, +2.1 cm/yr, and -1.9 cm/yr, was noted for pre-puberty, peri-puberty, and post-puberty patients, respectively, after starting ciclesonide.. Height velocity should be monitored closely during routine asthma visits to identify potential adrenal suppression associated with inhaled corticosteroids use. Ciclesonide is a good option for asthma treatment that allows for adrenal recovery.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Age Factors; Asthma; Body Height; Child; Female; Growth; Humans; Male; Pregnenediones

The long-acting anticholinergic tiotropium has recently been registered for the treatment of asthma, and its use is associated with a reduction in exacerbation frequency. Anti-inflammatory and anti-remodeling effects of tiotropium have been demonstrated in in vitro and in vivo models. Because tiotropium treatment is used in combination with inhaled corticosteroids, potential additive effects between the two would be clinically relevant. Therefore, the aim of this study was to investigate additive effects between tiotropium and ciclesonide on airway inflammation and remodeling in guinea pig models of asthma.. Guinea pigs (n = 3-8/group) were sensitized and challenged with ovalbumin in an acute (single challenge) and a chronic model (12 weekly challenges) of allergic asthma. Animals were treated with vehicle, nebulized tiotropium (0.01-0.3 mM) and/or intranasally instilled ciclesonide (0.001-1 mg/kg) before each challenge. Bronchoalveolar lavage fluid and lungs were collected for analysis of airway inflammation and remodeling.. Tiotropium and ciclesonide treatment, alone or in combination, did not inhibit airway inflammation in the acute asthma model. In a dose-finding study, low doses of tiotropium and ciclesonide inhibited airway eosinophilia and airway smooth muscle thickening in the chronic asthma model. Threshold doses of 0.01 mM tiotropium (nebulizer concentration) and 0.01 mg/kg ciclesonide were selected to investigate potential additive effects between both drugs. At these doses, tiotropium and ciclesonide did not inhibit airway eosinophilia or airway smooth muscle thickening when administered alone, but significantly inhibited these allergen-induced responses when administered in combination.. Combined treatment with low doses of tiotropium and ciclesonide inhibits airway inflammation and remodeling in a guinea pig model of chronic asthma, suggesting that combined treatment with anticholinergics and corticosteroids may have anti-inflammatory and anti-remodeling activity in allergic airway diseases. Since tiotropium is registered as a therapy for asthma added on to corticosteroid treatment, these beneficial effects of the combination therapy may be clinically relevant.

Topics: Administration, Inhalation; Airway Remodeling; Animals; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Guinea Pigs; Male; Ovalbumin; Pregnenediones; Tiotropium Bromide; Treatment Outcome

Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands.. Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 - 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1-year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting β2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models.. Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in μg) were 160 (160 - 320) for extrafine-particle versus 500 (250 - 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine-particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47-0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44-0.57]).. In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cohort Studies; Databases, Factual; Female; Fluticasone; Humans; Logistic Models; Male; Middle Aged; Netherlands; Particle Size; Pregnenediones; Treatment Outcome

Topics: Adolescent; Asthma; Australia; Bronchial Spasm; Glucocorticoids; Humans; Pregnenediones

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Female; Humans; Male; Pregnenediones

Effectiveness and safety profile of ciclesonide in the treatment of persistent allergic or non-allergic asthma was evaluated in real-life setting in Austria.. Prospective, single-arm, 3-month observational, non-interventional, open-label cohort study in patients with persistent asthma (with or without allergic component) of any severity grade was conducted. Patients were either treatment naïve or switched to treatment with ciclesonide and had an indication for treatment with inhaled corticosteroids.. In all, 307 patients (50.8% female; mean age, 45.7 years) were prescribed ciclesonide. After 3 months of observation, the percentage of patients with daily symptoms had declined from 33.2 to 3.9%, night-time symptoms from 21.8 to 5.2%, physical activity limitations from 73.9 to 24.4%, and rescue medication usage from 70.0 to 45.9%. The mean total Asthma Control Questionnaire (ACQ) score was 2.32 ± 1.14 at the first and 1.08 ± 0.88 at the final visit. The number of patients with well-controlled asthma (ACQ score < 1) increased considerably from 11.0% at baseline to 52.2% at study end. Clinically important mean improvements were observed in the total self-assessed Asthma Quality of Life score and all four domain scores. The mean forced expiratory volume in 1 s (FEV1) increased by 0.3 L from 2.60 ± 0.87 L to 2.89 ± 0.86 L, and the mean FEV1% predicted increased from 75.1 ± 15.4% to 83.7 ± 14.9%. Incidence of adverse drug reactions (ADRs) was low (4 ADRs in 3 of 307 patients, or 1.0%).. This study confirmed the effectiveness and safety of ciclesonide under routine conditions in Austria. Improvements in symptom control, lung function, and quality of life were observed. Ciclesonide was well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Asthma; Austria; Chronic Disease; Cohort Studies; Female; Humans; Hypersensitivity; Male; Middle Aged; Pregnenediones; Prospective Studies; Treatment Outcome; Young Adult

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Ethanolamines; Forecasting; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Muscarinic Antagonists; Pregnadienediols; Pregnenediones; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Inhaled corticosteroids such as beclometasone are the drugs of choice for long-term treatment of patients with persistent asthma. There is no tangible difference in efficacy among inhaled corticosteroids, but we have the most experience with beclometasone. Ciclesonide (Alvesco, Nycomed then Takeda), another inhaled cortico-steroid, has been tested in three double-blind trials versus budesonide and six trials versus fluticasone but none versus beclometasone. These trials showed the "non-inferiority" of ciclesonide, mainly in terms of a surrogate endpoint: the change in forced expiratory volume in one second (FEV1) after 12 or 24 weeks of treatment (primary endpoint). However, the doses of ciclesonide used in these trials were higher than the standard doses while doses of the comparator corticosteroids were lower than the standard doses, thus favouring ciclesonide. Local adverse effects of inhaled corticosteroids include oral candidiasis, sore throat and hoarseness. A systematic review conducted by a Cochrane group suggests that ciclesonide does not have a better adverse effect profile than other inhaled corticosteroids used at equivalent doses. Corticosteroid inhalation can also lead to systemic absorption. The practical advantage of once-daily dosing with ciclesonide seems minor. In practice, ciclesonide is neither more effective than the inhaled corticosteroids with which it has been compared, nor does it have fewer adverse effects. It is better to continue to use beclometasone, a drug with which there is more experience.

Topics: Administration, Inhalation; Asthma; Glucocorticoids; Humans; Pregnenediones; Time Factors

The choice among the different treatments available can have a great impact on the costs of asthma,. The objective of this study was to estimate the incremental cost-utility ratio of three inhaled corticosteroids (ICs): budesonide (BUD), fluticasone propionate (FP), and ciclesonide, compared to beclomethasone dipropionate (BDP) (the only IC included in the Compulsory Health Insurance Plan of Colombia),. A Markov-type model was developed to estimate costs and health outcomes of a simulated cohort of patients less than 18 years of age with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a systematic review of the literature. Cost data were obtained from a hospital´s bills and from the national manual of drug prices. The study assumed the perspective of the national healthcare in Colombia. The main outcome was the variable "quality-adjusted life years" (QALY), RESULTS: While treatment with BDP was associated with the lowest cost (£106.16 average cost per patient during 12 months), treatment with FP resulted in the greatest gain in QUALYs (0.9325 QALYs). FP was associated with a greater gain in QALYs compared to BUD and ciclesonide (0.9325 vs. 0.8999 and 0.9051 QALYs, respectively) at lower costs (£231.19 vs. £309.27 and £270.15, respectively), thus leading to dominance. The incremental cost-utility ratio of FP compared to BDP was £19,835.28 per QALY, CONCLUSIONS: BDP is the most cost-effective therapy for treating pediatric patients with persistent asthma when willingness to pay (WTP) is less than £21,129.22/QALY, otherwise, FP is the most cost-effective therapy.

Topics: Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Cohort Studies; Colombia; Computer Simulation; Cost-Benefit Analysis; Drug Costs; Female; Fluticasone; Humans; Male; Markov Chains; Models, Economic; Pregnenediones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic

Ciclesonide, an inhaled corticosteroid with almost no affinity for the glucocorticoid receptor, is highly effective in downregulating in vitro pro-inflammatory activities of airway parenchymal cells when converted into the active metabolite desisobutyryl-ciclesonide.. We evaluate whether ciclesonide could effectively downregulate also antigen- or allergen-induced activation of peripheral blood mononuclear cell and of allergen-specific T-cell blasts.. Peripheral blood mononuclear cells were isolated from non atopic and atopic asthmatic children sensitized to Phleum pratense (PhlP5). Proliferation toward Candida albicans or PhlP5 in the presence of ciclesonide or desisobutyryl-ciclesonide (0.003-3.0 μM) was evaluated as [(3)H]thymidine incorporation. Modulation of PhlP5-specific T-cell blasts proliferation and PhlP5-induced interleukin 4 expression by ciclesonide and desisobutyryl-ciclesonide were measured.. Peripheral blood mononuclear cell proliferation to C. albicans was dose-dependently inhibited by 0.3-3.0 μM ciclesonide and desisobutyryl-ciclesonide but inhibition by desisobutyryl-ciclesonide was higher. A significant proliferation to PhlP5 was observed only in cultures from atopic subjects: an effective downregulation was already detected at 0.03 μM ciclesonide and 0.003 μM desisobutyryl-ciclesonide (complete inhibition at 3 μM ciclesonide and 0.03 μM desisobutyryl-ciclesonide). 3 μM ciclesonide and desisobutyryl-ciclesonide reduced the PhlP5-specific T-cell blast proliferation and interleukin 4-producing cell proportion.. These in vitro data, obtained at concentrations similar to those reached in vivo at bronchial level, are in favor of an efficient inhibition of ciclesonide on the T-cell mediated response toward allergens. Additional studies are required to confirm these preliminary data on the reduced activity of the drug on allergen-specific T-cell blast activation that may have clinical relevance.

Topics: Allergens; Anti-Allergic Agents; Antigens, Plant; Asthma; Candida albicans; Cell Proliferation; Child; Female; Fungal Proteins; Humans; Immunization; Interleukin-4; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Phleum; Pregnenediones; T-Lymphocytes; Up-Regulation

Topics: Administration, Inhalation; Adult; Asthma; Budesonide; Cross Reactions; Dermatitis, Allergic Contact; Female; Glucocorticoids; Humans; Male; Middle Aged; Patch Tests; Pregnenediones

The efficacy and safety profile of ciclesonide (CIC) in the treatment of asthma was evaluated in a large patient population in a real-life setting in Germany.. 24,037 patients with persistent mild/moderate bronchial asthma were enrolled into three observational studies with identical design. Data were pooled and analyzed. Patients received ciclesonide (160 μg/day) and were observed for 3 months. FEV(1), PEF, NO, asthma episodes, use of rescue medication and adverse drug reactions (ADR) were recorded.. Mean (95% CI) FEV(1) significantly increased from 80.7 [80.5; 80.9]% of predicted at baseline to 90.1 [89.9; 90.2]% after 3 months (n = 20,297), mean PEF significantly increased from 338 [335; 340] l/min to 392 [390; 395] l/min (n = 8100). NO was significantly reduced from 53.6 [51.8; 55.4] ppb to 26.2 [25.2; 27.1] ppb (n = 971). The percentage of patients with daily symptoms declined from 24.3% to 1.9%, night-time symptoms from 13.3% to 1.3%, and β(2)-agonists use from 26.9% to 8.8%. ADRs were reported by 51 patients (0.2%). Most frequent ADRs were: dysphonia (n = 11), cough (n = 10), dyspnoea, throat irritation, and oral candidiasis (n = 5 each). 46 patients terminated the study prematurely, 41 due to ADR and 5 due to unknown/missing reason. One patient died due to cardiac failure (no causal relation).. These observational studies under real-life conditions support findings from controlled clinical studies regarding efficacy and tolerability of ciclesonide in patients with mild to moderate bronchial asthma. No unexpected ADRs were detected.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Asthma; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Germany; Humans; Male; Middle Aged; Nitric Oxide; Pregnenediones; Prospective Studies; Young Adult

Despite the fact that bronchioles are involved in asthma, there have been limited asthmatic cases showing marked centrilobular opacities on computed tomography (CT) chest scans. Systemic corticosteroids have been administered in such cases, but the efficacy of extra-fine particle inhaled corticosteroids has not been assessed.. A previously healthy 64-year-old man presented with a four-month history of productive cough and progressive dyspnea despite a combination therapy with inhaled salmeterol (50 μg bid) and fluticasone (500 μg bid), sustained-release theophylline, and pranlukast because of suspicion of asthma. Physical examination revealed wheezing at the end of forced expiration. High resolution CT chest scan showed diffuse centrilobular opacities, bronchiectatic changes, and bronchial wall thickening. Transbronchial lung biopsy, bronchoalveolar lavage fluid, and transbronchial biopsy all showed predominant eosinophil infiltrates, suggesting that eosinophilic inflammation across the entire airway tree caused the abnormal CT findings. Alveolar fraction of exhaled nitric oxide level, a non-invasive marker of eosinophilic peripheral airway inflammation, was also elevated. Because he refused systemic corticosteroids, inhaled ciclesonide (400 μg bid) and inhaled tiotropium were added on to his current medication under careful observation. His symptoms, pulmonary function and CT findings promptly improved, and he had fully recovered at follow-up.. Extra-fine particle inhaled corticosteroids could be an alternative approach in centrilobular opacities caused by eosinophilic peripheral airway inflammation.

Topics: Anti-Allergic Agents; Asthma; Eosinophils; Humans; Inhalation; Lung; Male; Middle Aged; Nitric Oxide; Pregnenediones; Pulmonary Alveoli; Scopolamine Derivatives; Tiotropium Bromide; Tomography, X-Ray Computed

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Formoterol Fumarate; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pregnenediones; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Adrenal suppression secondary to high-dose inhaled corticosteroid use has been reported in children.. The authors report the use of ciclesonide to reverse adrenal suppression secondary to inhaled fluticasone use in four pediatric patients.. In these four children, hypothalamic-pituitary-adrenal axis function normalized after the patients were changed to ciclesonide, while good asthma control was maintained.. Ciclesonide should be considered for the reversal of adrenal suppression secondary to the use of fluticasone, and perhaps other older inhaled corticosteroids as well.

Topics: Adrenal Cortex Hormones; Adrenal Glands; Asthma; Child, Preschool; Female; Humans; Infant; Male; Pregnenediones

Topics: Adolescent; Adult; Anti-Allergic Agents; Asthma; Female; Humans; Male; Pregnenediones; Young Adult

Topics: Anti-Allergic Agents; Asthma; Humans; Pregnenediones

Recent developments concerning pressurized metered dose inhalers (pMDIs) with inhaled corticosteroids (ICS) are the introduction of ciclesonide and the replacement of propellants. As the results of in vivo studies depend on pMDIperformance, it is necessary to evaluate pMDIs in vitro for delivered dose and particle size distributions under different conditions.. Fluticasone 125microg, budesonide 200microg, beclomethasone HFA100microg, and ciclesonide 160microg were compared for delivered dose and particle size using laser diffraction analysis with inspiratory flow rates of 10, 20 and 30l/s.. The volume median diameter of budesonide was 3.5microm, fluticasone 2.8microm, beclomethasone and ciclesonide both 1.9microm. The mouthpiece retention was up to 30% of the nominal dose for beclomethasone and ciclesonide, 11-19% for the other pMDIs. Lifespan, flow rate, and air humidity had no significant influence on particle size distribution. The delivered dose of beclomethasone, budesonide, and ciclesonide remained constant over the lifespan. The delivered dose of fluticasone 125 decreased from 106% to 63%; fluticasone 250 also decreased whereas fluticasone 50 remained constant.. There is a significant difference in median particle size distribution between the different ICS pMDIs. Air humidity and inspiratory flow rate have no significant influence on particle size distribution. Ciclesonide 160 and beclomethasone 100 deliver the largest fine particle fractions of 1.1-3.1microm. The changes in delivered dose during the lifespan for the fluticasone 125 and 250 may have implications for patient care.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Asthma; Beclomethasone; Budesonide; Drug Delivery Systems; Equipment Design; Fluticasone; Humans; Materials Testing; Metered Dose Inhalers; Particle Size; Pregnenediones

Although it is well established that the incidence of bronchial asthma is higher in the athlete population than in the general population, little information exists about the efficacy of treatment of bronchial asthma in the athlete population.. We conducted this study with the objective of determining the efficacy of treatment of bronchial asthma in an athlete population living in Niigata Prefecture, Japan.. We conducted a retrospective study of bronchial asthma in an athlete population. Athletes diagnosed as having asthma, based on the Global Initiatives for Asthma (GINA) guidelines, who visited the Niigata Institute for Health and Sports Medicine between January 2007 and June 2008 were enrolled in this study. We compared two groups of patients, a group treated with ciclesonide (CIC) alone and another treated with montelukast alone, with the treatment duration lasting at least 3 months in both groups. The CIC or montelukast groups were compared in terms of the clinical symptoms, pulmonary function parameters, and fraction of exhaled nitric oxide (FENO).. There were no significant differences in the sex distribution, age, frequency of symptoms, pulmonary function parameters, or other examination data before treatment between the CIC and montelukast groups. The CIC group tended to show better symptom control and to need fewer changes of treatment than the montelukast group. While improvements of the pulmonary function parameters and FENO values were observed in the CIC group, no significant changes of these parameters were observed in the montelukast group.. These data suggest that CIC offers greater promise for the control of asthma than montelukast in the athlete population, although further investigation is required.

Topics: Acetates; Adolescent; Asthma; Athletes; Breath Tests; Cyclopropanes; Female; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Nitric Oxide; Pregnenediones; Quinolines; Retrospective Studies; Sulfides; Treatment Outcome; Vital Capacity; Young Adult

Topics: Administration, Inhalation; Anti-Allergic Agents; Asthma; Cost of Illness; Drug Approval; Humans; Metabolic Clearance Rate; Patient Education as Topic; Patient Selection; Pregnenediones; United States; United States Food and Drug Administration

Topics: Anti-Allergic Agents; Asthma; Child; Child Development; Follow-Up Studies; Humans; Pregnenediones; Time Factors; Treatment Outcome

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Administration Schedule; Fluticasone; Humans; Metered Dose Inhalers; Pregnenediones; Treatment Outcome

Topics: Adrenal Cortex Hormones; Age Factors; Anti-Allergic Agents; Asthma; Humans; Metered Dose Inhalers; Pregnenediones

Ciclesonide is a modern inhaled corticosteroid registered for asthma treatment. It is delivered as an inactive prodrug and undergoes conversion to an active metabolite in the lungs. Ciclesonide has been formulated as an aerosol solution in a metered dose inhaler with hydrofluoralkane which characterizes a high deposition rate over 50%. Lots of clinical trials show that ciclesonide is effective in asthma control in a wide range of doses from 40 do 1280 mug/day in a dose-dependent manner. It reduces the need for systemic corticosteroids. Due to the unique pharmacokinetics, ciclesonide has a favorable safety profile both in the low and in the high doses. It is recommended by GINA in every case when the glucocorticosteroids are indicated, as a drug with reduced local and systemic side effects. This article is a review of clinical trials on efficacy and safety of ciclesonide as the resume of authors' clinical experience.

Topics: Anti-Allergic Agents; Asthma; Humans; Metered Dose Inhalers; Pregnenediones; Treatment Outcome

To examine the deposition and pharmacokinetics of ciclesonide administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) in patients with asthma.. Twelve patients with mild asthma (FEV1, 95% predicted) inhaled a single dose of 99mtechnetium (Tc)-ciclesonide 320 microg ex-actuator (400 microg ex-valve). Deposition of ciclesonide in the lung and oropharynx was quantified using two-dimensional (2D)-gamma scintigraphy. Three-dimensional single photon emission computed tomography (3D SPECT) was used to assess the regional distribution of ciclesonide in the lung. The pharmacokinetics of ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC), were determined by liquid chromatography-tandem mass spectrometry. Ciclesonide and des-CIC concentrations were determined in mouth-rinsing solutions.. 2D-gamma scintigraphy indicated that ciclesonide deposition was higher in the whole lung (52%) than in the oropharynx (32.9%). Furthermore, 3D SPECT revealed that ciclesonide deposition within the lungs was highest in the peripheral regions that contain the small airways and alveoli. The pharmacokinetic profile of Tc-labeled ciclesonide and des-CIC was similar to that obtained after inhalation of non-labeled formulations in previous studies. Des-CIC accounted for 14.9% of the total molar concentration of ciclesonide/des-CIC in mouth-rinsing solutions obtained between 7 and 12min after inhalation.. Inhalation of ciclesonide via HFA-MDI results in high pulmonary deposition, especially in the peripheral regions of the lung. High pulmonary deposition contributes to ciclesonide's ability to maintain lung function and control symptoms in patients with asthma. Deposition and activation of ciclesonide in the oropharynx is low, consistent with previous reports of low oropharyngeal deposition and a reduced incidence of local side effects in patients receiving ciclesonide therapy.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Cohort Studies; Female; Gas Chromatography-Mass Spectrometry; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Oropharynx; Pregnenediones; Technetium; Tomography, Emission-Computed, Single-Photon

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Clinical Trials as Topic; Humans; Pregnenediones; Treatment Outcome

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Biological Availability; Dose-Response Relationship, Drug; Forced Expiratory Volume; Humans; Pregnenediones; Product Surveillance, Postmarketing; Treatment Outcome

Topics: Administration, Inhalation; Aerosols; Anti-Asthmatic Agents; Asthma; Drug Administration Schedule; Humans; Pregnenediones

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Delayed-Action Preparations; Drug Administration Schedule; Humans; Lung; Pregnenediones

Inhaled glucocorticosteroids are the first choice drugs in the treating of patients with chronic bronchial asthma. Despite the fact that they are considered safe, in some percentage of patients they may cause local and even systemic side effects. Most of those side effects result from low lung / body deposition index of many glucocorticosterois and action of active metabolites of the drugs already in the oral cavity and throat. Ciclesonide is a new steroid characterized by clinical efficacy comparable to that of fluticasone and a lower risk of side effects. Ciclesonide is a prodrug, which is converted into an active metabolite by lung esterases only in the peripheral airways. Due to the use of a novel aerosol propellant--hydrofluoroalkane, available ciclesonide preparations are characterized by a high lung deposition. It is also characterized by low absorption to the systemic circulation. The article presents an current knowledge on pharmacokinetics, clinical efficacy and safety of ciclesonide in patients with bronchial asthma.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Humans; Lung; Pregnenediones

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Clinical Trials as Topic; Humans; Lung; Pregnenediones; Treatment Outcome

Ciclesonide is a novel glucocorticoid that is converted into ciclesonide--active principle (CIC-AP) in the lung. The study objectives were to identify a structural model for population pharmacokinetic (PK) analysis of CIC-AP using nonlinear mixed-effects modeling, assess the influence of select covariates on PK and/or pharmacodynamic (PD) parameters, and investigate the effects of CIC-AP on endogenous cortisol. Pooled concentration data from nine phase I studies (dose: 400-3600 micrograms) involving healthy and asthmatic patients were included in the PK analysis. There were 151 subjects (3300 observations) for the CIC-AP population PK analysis. Various models examined inter- and intrasubject variability for the PK parameters. Population estimates of the PK parameters of clearance and volume of distribution were 396 L/h (64.8% co-efficient of variation [CV]) and 1190 L (41.2% CV), respectively. Pharmacodynamic population estimates included maximum cortisol release rate, 3140 ng/h (5.4% CV). The EC50 of CIC-AP was 0.88 ng/mL. Ciclesonide is a safe corticosteroid that causes negligible cortisol suppression. The disposition and effect of CIC-AP can be described using mixed-effect modeling. The estimated EC50 is similar to mean Cmax from an 800-micrograms dose, further suggesting CIC-AP has little effect on cortisol suppression.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Clinical Trials, Phase I as Topic; Data Interpretation, Statistical; Female; Humans; Hydrocortisone; Male; Middle Aged; Models, Biological; Pregnenediones

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Humans; Lung; Patient Acceptance of Health Care; Pregnenediones; Time Factors

Topics: Anti-Asthmatic Agents; Asthma; Clinical Trials, Phase III as Topic; Humans; Placebos; Pregnenediones; Time Factors

Topics: Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Humans; Pregnenediones; Randomized Controlled Trials as Topic; Time Factors

Topics: Anti-Asthmatic Agents; Asthma; Humans; Pregnenediones; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal