Biomedical subjects

Donald Banerji

Publications and source records attributed to Donald Banerji.

6 recordsLinked to original sources

PubMed2006

Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma.

STUDY OBJECTIVES: Oral corticosteroids (OCS) may be associated with systemic adverse events (AEs), which can be reduced by replacing OCS with inhaled corticosteroids (ICS). The potential of ciclesonide, a novel ICS, to reduce OCS use in patients with severe, persistent asthma was evaluated in this study. DESIGN: A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study. PATIENTS: Adult and adolescent patients (> or = 12 years old; n = 141) with severe, persistent, oral steroid (prednisone)-dependent asthma. INTERVENTIONS: Patients were 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. MEASUREMENTS AND RESULTS: The prednisone dose was significantly reduced by 47% and 63% in the groups receiving ciclesonide, 640 microg/d, and ciclesonide, 1,280 microg/d, respectively, vs an increase of 4% in the placebo group (both p < or = 0.0003) at week 12. By week 12, prednisone was discontinued by approximately 30% of patients in the ciclesonide-treated groups, vs 11% of patients in the placebo group (both p < or = 0.04). FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo (p < 0.03). The occurrence of local and systemic AEs was comparable between all treatment groups. CONCLUSION: Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe, persistent asthma, while maintaining asthma control.

Administration, Oral↗

PubMed2005

Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma.

BACKGROUND: Inhaled corticosteroids are recommended as first-line therapy for persistent asthma. OBJECTIVE: We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma. METHODS: An integrated analysis of 2 identical, multicenter, double-blind, 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. RESULTS: All ciclesonide groups showed significant improvements from baseline to week 12 in FEV1 compared with the placebo group (CIC80, 0.12 L [P = .0007]; CIC160, 0.13 L [P = .0004]; and CIC320, 0.14 L [P < .0001]). Likewise, FEV1 percent predicted, morning and evening peak expiratory flow, 24-hour asthma symptom score, daily albuterol use, and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group. Overall ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group. Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events, and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group. No suppression of hypothalamic-pituitary-adrenal-axis function (as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [1 microg] cosyntropin) was observed with any dose of ciclesonide. CONCLUSIONS: In this integrated analysis, ciclesonide once daily administered in the morning is effective and well tolerated.

Adult↗

PubMed2005

Ciclesonide, a novel inhaled steroid, does not affect hypothalamic-pituitary-adrenal axis function in patients with moderate-to-severe persistent asthma.

BACKGROUND: Inhaled corticosteroids (ICSs) reduce local airway inflammation, which is an underlying cause of asthma symptoms. However, potential systemic side effects associated with ICS use are a major concern for asthmatic patients. METHODS: Adult patients (n = 60; > or = 18 years of age) with moderate-to-severe asthma were 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]. RESULTS: After 29 days of treatment, CIC 640, CIC 1280, and FP 880 had no significant effect on the mean serum cortisol area under the curve for 0 to 24 h (AUC0-24h). FP 1760 produced a statistically significant suppression in mean serum cortisol AUC0-24h compared to PBO (p = 0.0009; 95% confidence interval [CI] -117.5 [corrected] to -32.1). Results obtained with cosyntropin stimulation revealed no statistically significant differences among the groups. The CIC 640 group demonstrated a significant increase compared to the PBO group in 24-h urinary cortisol levels from baseline at week 4 (p = 0.0224; 95% CI, 0.0023 to 0.0283), while the other treatment groups revealed no change in this parameter. The incidence of treatment-emergent adverse events was similar in all groups, and all adverse events were mild or moderate in severity. CONCLUSION: Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO.

Administration, Inhalation↗

PubMed2004

Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective.

Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High lung deposition/targeting, high receptor binding, longer pulmonary retention, and high lipid conjugation are among the pharmacokinetic parameters to be considered for improved efficacy of the compound. Low or negligible oral bioavailability, small particle size and inactive drug at the oropharynx, high plasma protein binding, rapid metabolism, high clearance, and lower systemic concentrations are associated with low risks for adverse effects. Inhaled glucocorticoid potency is enhanced by solution inhalers, which result in higher pulmonary deposition and minimize local adverse effects. These properties, among others, determine the efficacy and safety of inhaled glucocorticoids. Currently available inhaled glucocorticoids do not provide the complete pharmacokinetic/pharmacodynamic parameters to optimize RBV, leaving room for improvement in the development of future agents.

Administration, Inhalation↗

PubMed2003

The effects of intranasal triamcinolone acetonide and intranasal fluticasone propionate on short-term bone growth and HPA axis in children with allergic rhinitis.

OBJECTIVE: The purpose of this study was to evaluate the effects of triamcinolone acetonide (TAA) and fluticasone propionate (FP) aqueous nasal sprays on short-term lower-leg growth velocity and hypothalamic-pituitary-adrenal (HPA-axis function in pediatric subjects. METHODS: In this controlled, double-blinded (TAA) or single-blinded (FP), four-way crossover trial, 59 subjects (mean age: 7.2 years) were randomized to receive each of four 2-week treatments in random order: TAA nasal spray 110 microg, TAA nasal spray 220 microg, FP nasal spray 200 microg, and placebo, administered by a third party once daily with a 2-week washout period between treatments. Lower-leg growth velocity was measured by knemometry, and HPA-axis function was measured using 12-hour overnight urinary cortisol levels. RESULTS: Forty-nine subjects completed all four treatments and were included in the analyses. Mean growth velocity (+/- standard error) was 0.46 (+/- 0.06) mm/week for placebo, 0.37 (+/- 0.06) and 0.31 (+/- 0.06) mm/week for TAA nasal spray 110 and 220 microg, respectively, and 0.37 (+/- 0.06) mm/week for FP nasal spray. The treatment effect on mean growth velocity compared with placebo was -19.6% with TAA 110 microg, -32.6% with TAA 220 microg, and -21.7% with FP; none of these effects was considered statistically or clinically significant according to predefined criteria. No significant differences in changes in urine cortisol/creatinine ratios were observed between TAA 110 microg or 220 microg and placebo (4.38, 3.60, and -0.67, respectively, P > or = 0.157). In contrast, the change in mean urine cortisol/creatinine ratio values for FP (-3.59) were significantly lower compared with TAA 220 microg (P = 0.033) and placebo (P = 0.003). Knemometry exhibited less time-dependent variability than overnight urinary cortisol measurements. CONCLUSIONS: Neither TAA nor FP had a clinically significant effect on lower-leg growth velocity. In contrast to FP, TAA nasal spray did not significantly affect HPA-axis function when used over a 2-week interval.

Administration, Intranasal↗

PubMedDate not supplied

Safety and clinical relief over 1 year with triamcinolone acetonide hydrofluoroalkane-134a nasal aerosol in patients with perennial allergic rhinitis.

The intranasal corticosteroid triamcinolone acetonide (TAA) is an effective treatment for allergic rhinitis (AR). A new hydrofluoroalkane-134a (HFA)-propelled formulation (TAA-HFA) has been approved recently. This study assessed the safety and efficacy of TAA-HFA in patients with perennial AR over 1 year. A total of 396 patients aged 12-69 years with perennial AR (PAR) enrolled in this 1-year, open-label study. Patients received TAA-HFA, 220 microg, once daily for 2 weeks before adjusting their dose to 440 or 110 microg once daily as needed to control symptoms. Doses were standardized to 440 microg across all patients at approximately 4 months. Physical examinations, vital signs, and laboratory measurements were conducted at baseline, 6 months, and study end. Patient and physician global symptom evaluations were performed at visits 3-10. Patients recorded any adverse events (AEs) on daily diary cards. Of the 396 patients enrolled, 349 (88.1%) reported AEs. The most frequently reported AEs were pharyngitis, rhinitis, local reactions, headache, epistaxis, and sinusitis. Most AEs were mild to moderate in intensity; 34 patients discontinued because of AEs. There were no clinically relevant changes in physical examinations, vital signs, or laboratory measurements. A total of four serious AEs were reported; all were recorded as not related to study drug. Mean patient and physician scores of symptom relief showed significant relief from week 2 (visit 3) through the final visit. Long-term administration of TAA-HFA, 440 microg, exhibited a good safety and tolerability profile, while providing moderate-to-complete symptom relief as rated by patients and physicians.

Administration, Intranasal↗