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Background A new, hydrofluoroalkane nasal aerosol solution formulation of ciclesonide (CIC-HFA) delivered via a metered dose inhaler is currently in clinical development for treatment of allergic rhinitis. Objective To study tolerability and quality of life following administration of CIC-HFA 74- or 148-μg doses once-daily compared with placebo in patients with perennial allergic rhinitis (PAR) over 26 weeks. Methods Patients ≥12 years of age with a ≥2 year history of PAR were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 μg, 148 μg, or placebo QD AM for 26 weeks. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs). Quality of life was assessed by using a rhinoconjunctivitis quality of life questionnaire with standardized activities (RQLQ[S]) in patients with baseline RQLQ ≥3.00. Reflective total nasal symptom scores (rTNSS) and instantaneous total nasal symptom scores (iTNSS) over 26 weeks were also evaluated. Results In this study, 1111 patients were randomized. The overall incidence of TEAEs was comparable between the treatment groups. Treatment with CIC-HFA 74- or 148-μg doses showed improvements in RQLQ[S] [least squares (LS) mean change 0.40 and 0.37, respectively from baseline, p < 0.01 versus placebo for both], rTNSS (LS mean change 0.65 and 0.52, respectively from baseline; p ≤ 0.01 versus placebo for both), and iTNSS (LS mean change 0.51 and 0.42, respectively from baseline; p < 0.05 versus placebo for both) from baseline. Conclusion In this study, once-daily treatment with CIC-HFA 74- or 148-μg doses over 26 weeks was well tolerated with comparable incidence of TEAEs between the treatment groups.

A nasal aerosol formulation of ciclesonide with a hydrofluoroalkane propellant (CIC-HFA) is currently in development for treatment of allergic rhinitis (AR). This study evaluated the efficacy and safety of once-daily administration of CIC-HFA 74 or 148 micrograms compared with placebo in patients with seasonal AR (SAR) from mountain cedar pollen. Patients ≥12 years of age with a ≥2-year history of SAR from mountain cedar pollen were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo once daily in the morning for 2 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous TNSS (iTNSS), and reflective total ocular symptom score (rTOSS) in patients with baseline rTOSS ≥5.00 were evaluated. Adverse events (AEs) were monitored throughout the study. A statistically significant improvement in rTNSS (least squares [LS] mean change from baseline 1.04 and 1.02 respectively; p < 0.0001 versus placebo for both) and iTNSS (LS mean change from baseline 0.90 and 0.83 respectively; p < 0.001 vs placebo for both) was observed after treatment with CIC-HFA 74- or 148-microgram doses. Only the CIC-HFA 74-micrograms treatment group showed a statistically significant improvement in rTOSS (LS mean change from baseline 0.52; p = 0.0124) compared with placebo. The overall incidence of AEs was low and comparable between the treatment groups. In this study, statistically significant improvements in nasal symptoms of SAR were observed after treatment with CIC-HFA 74-microgram or CIC-HFA 148-microgram doses. Both active treatments were well tolerated. Clinical trial registry URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01010971.

Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is currently in development for treatment of allergic rhinitis. This Phase I study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of CIC-HFA in healthy subjects (N = 18) and subjects with perennial allergic rhinitis (PAR, N = 18) in a double-blind, placebo-controlled, 3-period crossover design following treatment with 282 μg or 148 μg CIC-HFA or placebo once-daily for 14 days. The concentrations of desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of CIC were measured by a validated high performance liquid chromatography with tandem mass spectrometry. Maximum serum concentration (C(max)), area under the serum concentration time curve (AUC), time to maximum serum concentration (t(max)) and elimination half life (t(1/2)) where feasible, were calculated. Serum cortisol (AUC(0-24h)) and adverse events (AE) were also evaluated. The overall systemic exposure of des-CIC was low. The mean C(max) for des-CIC on Day 14 was 35.84 ng/L and 25.98 ng/L for the CIC-HFA 282 μg and CIC-HFA 148 μg treatment groups respectively. Mean AUC((0, last)) for des-CIC on Day 14 was 213 ng·h/L and 112.3 ng·h/L for CIC-HFA 282 μg and 148 μg respectively. Mean serum cortisol (AUC(0-24h)) was similar for CIC-HFA 282 μg (178 μg·h/dL), CIC-HFA 148 μg (169 μg·h/dL), and placebo (174 μg·h/dL) on Day 14. The overall incidence of AEs was low and headache and epistaxis were the most common individual AEs reported. In this study, systemic exposure of des-CIC was low and similar in healthy subjects and subjects with PAR with no evidence of clinically relevant accumulation over the 14 day treatment period in either treatment group. Both doses of CIC-HFA were well tolerated without significant effect on cortisol levels.

A new nasal aerosol solution formulation of ciclesonide containing a hydrofluoroalkane propellant (CIC-HFA) delivered via a metered-dose inhaler is currently in clinical development as a potential treatment for allergic rhinitis (AR). This study evaluated the efficacy and tolerability of CIC-HFA 74- or 148-microgram doses compared with placebo in patients with perennial AR (PAR). Patients ≥12 years of age with a ≥ 2-year history of PAR were randomized in a placebo-controlled, double-blind, parallel-group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo q.d. in the morning (A.M.) for 26 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), and rhinoconjunctivitis quality-of-life questionnaire with standardized activities (RQLQ[S]) in patients with baseline RQLQ of ≥3.00 were evaluated for the first 6 weeks of treatment. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. Eleven hundred eleven patients were randomized. CIC-HFA 74- and 148-microgram doses showed statistically significant improvements in rTNSS (least squares [LS] mean change, 0.70 and 0.54, respectively; p ≤ 0.001 versus placebo for both), iTNSS (LS mean change, 0.58 and 0.42, respectively; p < 0.05 versus placebo for both), and RQLQ[S] (LS mean change, 0.55 and 0.37, respectively; p < 0.01 versus placebo for both) from baseline. The overall incidence of TEAEs was comparable between the CIC-HFA treatment groups and placebo. In this study, once-daily treatment with CIC-HFA 74- or 148-micrograms showed statistically significant improvements in nasal symptoms of PAR. Both doses were well tolerated. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT00953147.

A hypotonic aqueous nasal spray of ciclesonide is indicated for the treatment of allergic rhinitis (AR). A new nasal aerosol formulation of ciclesonide containing a hydrofluoroalkane propellant delivered via a metered-dose inhaler (CIC-HFA) is currently in clinical development as a potential treatment for AR.To study the efficacy and safety of once-daily administration of CIC-HFA 80 or 160 μg compared with placebo in subjects 12 years and older with seasonal AR (SAR).Subjects 12 years and older with a ≥ 2-year history of SAR were randomized in a placebo-controlled, double-blind, parallel-group, multicenter study to receive CIC-HFA 80 or 160 μg or placebo once daily in the morning for 2 weeks. Changes from baseline in reflective total nasal symptom scores (rTNSSs), instantaneous TNSSs (iTNSSs), and reflective total ocular symptom scores (rTOSSs) in subjects with a baseline rTOSS of ≥ 5.00 were evaluated. Treatment-emergent adverse events were monitored throughout the study.Seven hundred seven subjects were randomized. From baseline, CIC-HFA 80 or 160 μg demonstrated 15.1% and 16.0% reductions in rTNSSs (P.0001, 3.7% for placebo), 14.3% and 15.4% reductions in iTNSSs (P.0001, 3.9% for placebo), and 15.7% and 15.0% reductions in rTOSSs (P.001, 6.8% for placebo). The overall incidence of treatment-emergent adverse events was low and comparable between the CIC-HFA and placebo groups.In this study, once-daily treatment with CIC-HFA 80 or 160 μg demonstrated statistically significant improvements in nasal and ocular symptoms of SAR. Both doses of active treatment were well tolerated.