Multidose Dry Powder Inhaler Research Articles

Albuterol multidose dry powder inhaler efficacy and safety versus placebo in children with asthma

Albuterol multidose dry powder inhaler efficacy and safety versus placebo in children with asthma

Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir® Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies

Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI. Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 μg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0-6) after dosing (Study 2). Study 1: differences, with corresponding 90% confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated. The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.

Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN). Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. Conclusions: The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma.

Novel albuterol multidose dry powder inhaler in patients with exercise-induced bronchoconstriction: A single-dose, double-blind, randomized, 2-way crossover study

BackgroundA novel, inhalation-driven, multidose dry powder inhaler (MDPI) was developed that eliminates the need to coordinate device actuation with inhalation as is required with conventional metered-dose inhalers. ObjectiveTo evaluate albuterol MDPI efficacy and safety in patients with exercise-induced bronchoconstriction (EIB). MethodsThis single-dose, double-blind, 2-way crossover study randomized adolescents and adults with EIB (≥20% fall from pre-exercise challenge FEV1) to treatment sequences of albuterol MDPI (180 μg [2 inhalations of 90 μg each])/placebo MDPI (n = 19) or the reverse sequence (n = 19). FEV1 was measured 30 and 5 min predose, 30 min postdose (ie, 5 min before treadmill exercise challenge; baseline) and 5, 10, 15, 30, and 60 min after exercise challenge. The primary efficacy endpoint was maximum percentage fall from baseline in FEV1 up to 60 min post-exercise challenge. ResultsMean maximum percentage fall in FEV1 within 60 min post-exercise challenge was 6.2 ± 1.4% for albuterol MDPI versus 22.4 ± 1.4% for placebo MDPI (between-treatment difference: −16.2%; 95% CI: −20.2% to −12.1%; P < 0.0001). A significantly higher percentage of albuterol MDPI–treated patients were protected against EIB (<10% maximum FEV1 fall post-exercise challenge) versus placebo MDPI (84.2% vs 15.8%; P < 0.0001). Protection with albuterol MDPI was evident within 5 min and maintained through 30 min; recovery was complete for both groups at 60 min. Treatment with a single dose of albuterol MDPI was generally well tolerated. ConclusionsAlbuterol MDPI provides clinically significant protection from EIB in adolescents and adults with EIB; no new safety issues were observed with short-term albuterol MDPI use. ClinicalTrials.gov identifier NCT01791972.

Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler.

A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 μg/inhalation × two inhalations (800 μg total dose); Fp DPI 250 μg/inhalation × four (1000 μg total dose); and Fp MDI 220 μg/inhalation × four (880 μg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t½]), safety, and tolerability were assessed for each treatment. Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 μg were 19% and 18% higher, respectively, compared with Fp DPI 1000 μg, and 47% and 82% higher, respectively, compared with Fp MDI 880 μg. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Single-dose administration of Fp MDPI 800 μg produced systemic exposure comparable with those for Fp DPI 1000 μg and Fp MDI 880 μg.

Budesonide inhaler device switch patterns in an asthma population in Swedish clinical practice (ASSURE).

Dry powder inhaler (DPI) device switch in asthma treatment could potentially increase with the entrance of new devices. We examined the switch patterns of budesonide (BUD) DPI analogues available in Sweden. This observational real-life study linked primary healthcare medical records data from the Västra Götaland region to national Swedish registries, and included asthma patients (ICD-10-CM J45) prescribed BUD in a multidose DPI. Index date: first dispense of BUD DPI. Switch date: prescription of another BUD DPI device. Study outcomes (switch vs. non-switch) were exacerbations and prescription of short-acting β2 -agonists. Study period was 1 July 2005 to 31 October 2013. Overall, 15,169 asthma patients were on treatment with BUD DPI; 1178 (7.35%) switched to another BUD DPI during the study. Pair-wise 1:1 matching of switchers vs. non-switchers resulted in two groups of 463 patients each (mean age 36 years, 55% female patients). A 25% higher exacerbation rate was seen postswitch (0.40 vs. 0.32; p = 0.047). Switchers were 4.5 year younger and had lower medication possession rate than non-switchers. Switch without primary healthcare visit did not differ between groups regarding consultations and exacerbations (no visit 4.96 and 0.90; visit 4.29 and 0.77, respectively). However, patients without primary healthcare visit at switch had significantly more outpatient hospital visits (2.01 vs. 0.81; p < 0.001). Considering the low switch rate, asthma patients and physicians in Swedish general practice seem reluctant to switch to another BUD DPI device. Switch, especially without primary healthcare visit, was associated with decreased asthma control resulting in higher exacerbation rate and more outpatient hospital visits.

Randomized equivalence trial: A novel multidose dry powder inhaler and originator device in adult and adolescent asthma.

Guideline-defined asthma control can be achieved and maintained in patients by treatment with fluticasone propionate-salmeterol (FP-Sal). To compare the efficacy and safety of FP-Sal delivered via a novel multidose dry powder inhaler (mDPI) versus an originator device in adolescent and adult patients with moderate-to-severe persistent asthma. Patients ages 12-65 years (N = 555) were randomized to treatment with FP-Sal novel mDPI 100 μg-50 μg or 500 μg-50 μg, or originator device 100 μg-50 μg or 500 μg-50 μg in a double-blind, double-dummy, parallel-group, multicenter study. Primary efficacy measures were absolute change in forced expiratory volume in 1 second (FEV1) from baseline and the area under the 12-hour serial FEV1 curve at the end of 12 weeks of treatment. Secondary end points included mean changes in FEV1; FEV1 % predicted; morning predose peak expiratory flow; daytime, nighttime, total asthma symptom scores; rescue medication use; percentage of patients with guideline-defined controlled asthma; global efficacy evaluation; patients' device preference; and safety. FP-Sal mDPI and originator device-mediated increases in FEV1 from baseline to the end of treatment were not significantly different, difference in least squares mean, -0.065 L (95% confidence interval, -0.154 to 0.024 L) at 100 μg-50 μg, and -0.032 L (95% confidence interval, -0.121 to 0.057 L) at 500 μg-50 μg). Both doses of FP-Sal mDPI improved FEV1 area under the 12-hour serial FEV1 curve from baseline and all secondary efficacy measures with no significant differences from the originator device at equivalent doses, with similar safety profiles. FP-Sal mDPI demonstrated equivalent efficacy and safety profile to the originator device and is an alternative in this patient group.

Comparison of the Pharmacokinetics of Salmeterol and Fluticasone Propionate 50/100 µg Delivered in Combination as a Dry Powder Via a Capsule-Based Inhaler and a Multi-Dose Inhaler.

The Rotacaps(®)/Rotahaler(®) system is a single unit dose inhaler being developed to deliver inhaled salmeterol/fluticasone propionate combination (SFC) as an alternative treatment option to the metered dose inhaler and the multi-dose dry powder inhaler, Diskus(®). The aim of this study was to compare the systemic exposure of SFC 50/100 µg following delivery via the Rotacaps(®)/Rotahaler(®) and the Diskus(®). This was an open-label, randomized, cross-over, repeat-dose (3.5 days of twice-daily dosing) study comparing salmeterol and fluticasone propionate systemic exposure following inhaled SFC 50/100 µg delivered via the Rotacaps(®)/Rotahaler(®) and Diskus(®), in healthy subjects. Pharmacokinetic sampling was conducted over 12 h post-dose on the last day of each treatment. Pharmacokinetic samples were analysed using solid phase extraction followed by high performance liquid chromatography/tandem mass spectrometry. Co-primary endpoints were fluticasone propionate area under the concentration-time curve over the dosing interval (AUC0-τ ) and salmeterol maximum plasma concentration (C max) on the last day of treatment. Following SFC 50/100 µg Rotacaps(®)/Rotahaler(®), fluticasone propionate and salmeterol systemic exposures were comparable with Diskus(®) in terms of both AUC0-τ [geometric mean ratio (GMR) with 90 % confidence interval (CI) of Rotahaler(®)/Diskus(®) for fluticasone propionate: 0.98 (0.91, 1.06) and salmeterol: 1.04 (0.99, 1.10)] and C max [GMR (90 % CI) for fluticasone propionate: 1.04 (0.94, 1.15) and salmeterol: 0.97 (0.87, 1.08)], meeting the pre-defined criteria for comparability (upper limit of the 90 % CI for the GMRs (Rotahaler(®)/Diskus(®)) ≤1.25]. SFC delivered from both inhalers was well tolerated. SFC 50/100 µg Rotacaps(®)/Rotahaler(®) showed comparable fluticasone propionate and salmeterol systemic exposure to Diskus(®) for all pharmacokinetic endpoints with GMR and both upper and lower limits of 90 % CIs within conventional acceptance criteria for bioequivalence (0.8, 1.25), sufficient for considering progression of the Rotacaps(®)/Rotahaler(®) product for further clinical development.

Dose-Ranging Study to Evaluate the Efficacy and Safety of Four Doses of Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler (FS MDPI) Compared with Fluticasone Propionate (Fp) Mdpi and FS DPI in Subjects with Persistent Asthma

Dose-response efficacy/safety study of 4 single-dose regimens of fluticasone/salmeterol multidose dry-powder inhaler (FS MDPI) versus fluticasone propionate (Fp) MDPI and FS dry powder inhaler (DPI) in subjects with asthma.

Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus Diskus and metered-dose inhalers.

A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp Diskus (a dry powder inhaler) and a metered-dose inhaler (MDI) in healthy subjects. This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 micrograms/inhalation X two inhalations (800 micrograms total dose); Fp Diskus 250 micrograms/inhalation X four (1000 micrograms total dose); and Fp MDI 220 micrograms/inhalation X four (880 micrograms total dose). Pharmacokinetics (area under concentration-versus- time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t1⁄2]), safety, and tolerability were assessed for each treatment. Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC 0-t and Cmax for Fp MDPI 800 micrograms were 19% and 18% higher, respectively, compared with Fp Diskus 1000 micrograms, and 47% and 82% higher, respectively, compared with Fp MDI 880 micrograms. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Single-dose administration of Fp MDPI 800 micrograms produced systemic exposure comparable with those for Fp Diskus 1000 micrograms and Fp MDI 880 micrograms.

Umeclidinium/vilanterol: a review of its use as maintenance therapy in adults with chronic obstructive pulmonary disease.

Umeclidinium/vilanterol (Anoro(®) Ellipta™; Laventair™) is an inhaled fixed-dose combination of a long-acting muscarinic receptor antagonist and a long-acting β2-adrenoceptor agonist. It is available in several countries, including Japan, the USA, Canada and those of the EU, where it is indicated for oral inhalation in adults with chronic obstructive pulmonary disease (COPD). Umeclidinium/vilanterol is administered once daily using the Ellipta™ multi-dose dry powder inhaler, which is regarded as easy to use. Umeclidinium/vilanterol (62.5/25µg once daily, equivalent to a delivered dose of 55/22µg once daily) was effective and well tolerated in adult patients with COPD participating in large, multicentre trials of up to 24weeks' duration. Umeclidinium/vilanterol improved pulmonary function to a significantly greater extent than placebo and each of the individual components. Moreover, umeclidinium/vilanterol was significantly more effective than once-daily tiotropium bromide monotherapy and a twice-daily fixed combination of salmeterol/fluticasone propionate at improving pulmonary function. Umeclidinium/vilanterol also had beneficial effects on dyspnoea, use of rescue medication, exacerbations, health-related quality of life and, in one study, exercise endurance. Umeclidinium/vilanterol is generally well tolerated in patients with COPD, with the most common adverse events in clinical trials being headache and nasopharyngitis. Umeclidinium/vilanterol was not associated with a clinically relevant increased risk of cardiovascular adverse events in patients with COPD, when data from several clinical trials were pooled. Thus, inhaled umeclidinium/vilanterol extends the treatment options currently available for the maintenance treatment of adults with COPD and has the convenience of once-daily administration.

Pharmacokinetics of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler

AimTo compare salmeterol (SALM) and fluticasone propionate (FP) systemic exposure following inhaled salmeterol/fluticasone propionate combination (SFC) from a unit-dose capsule-based inhaler (Rotacaps®/Rotahaler®) and a multi-dose dry powder inhaler (Diskus®) in healthy volunteers. MethodsAn open-label, randomised, repeat-dose, cross-over, adaptive design study (n = 36 in each part) evaluated SFC 50/250 μg and SFC 50/100 μg in Rotacaps used with two types of Rotahaler inhalers (airflow resistance similar to (S) and lower than (L) Diskus) versus the Diskus. Primary endpoints were area under the concentration-time curve over the dosing interval [AUC0–τ] and maximum plasma concentration [Cmax]. ResultsSFC 50/250 μg Rotacaps/Rotahaler (S) showed 1.2–1.9-fold greater FP and SALM systemic exposure compared with Diskus. FP and SALM systemic exposure were comparable to DISKUS following SFC 50/250 μg Rotacaps/Rotahaler (L) (90% CI of ratio of Rotahaler to DISKUS within 0.8–1.25) for salmeterol (AUC0–τ and Cmax) and FP (AUC0–τ). Following SFC 50/100 μg Rotacaps/Rotahaler (L), FP and SALM systemic exposures were 1.2–1.4 fold higher in terms of FP (AUC0–τ and Cmax) and salmeterol (Cmax) compared with Diskus. SFC at both doses and via both inhalers was well tolerated. ConclusionsSFC 50/250 μg Rotacaps/Rotahaler (L) showed comparable systemic exposure to Diskus in terms of FP AUC and SALM AUC and Cmax. These results merit further progression of SFC 50/250 μg Rotacaps/Rotahaler (L) to phase 3 clinical evaluation in asthma and COPD patients. The lack of pharmacokinetic comparability between the inhalers for SFC 50/100 μg requires further evaluation.

Genuair(®) in chronic obstructive pulmonary disease: a novel, user-friendly, multidose, dry-powder inhaler.

Inhaled corticosteroids and bronchodilators, which are pivotal to the management of respiratory diseases, are delivered by numerous devices, including pressurized metered-dose inhalers and dry-powder inhalers. However, patient adherence to these medications is suboptimal and incorrect inhaler technique is endemic, meaning that insufficient drug quantities are frequently delivered to the lungs. Genuair(®) (Almirall SA, Spain) is a novel, breath-actuated, multidose dry-powder inhaler designed to achieve reliable and effective delivery of inhaled medicines - including aclidinium bromide - to patients with chronic obstructive pulmonary disease. In addition to describing Genuair's design, which incorporates multiple feedback mechanisms in order to confirm effective medication uptake, this article discusses the performance characteristics of the inhaler, its efficiency in terms of drug deposition and the results of recent patient preference and satisfaction studies.

Pharmacokinetics and Pharmacodynamics of Fluticasone Propionate and Salmeterol Delivered as a Combination Dry Powder from a Capsule-Based Inhaler and a Multidose Inhaler in Asthma and COPD Patients

The object of this study was to assess whether a capsule-based and multidose dry powder inhaler containing salmeterol (as xinafoate salt) 50 μg plus fluticasone propionate (FP) 250 μg [combination (SFC 50/250)] could be equivalent in terms of in vivo drug delivery and systemic exposure. This was a randomized, double-blind, double-dummy, replicate treatment design comparative bioavailability study of SFC 50/250 delivered in a capsule-based inhaler (Rotahaler®) and a multidose dry powder inhaler (Diskus®). Subjects with asthma or chronic obstructive pulmonary (COPD) disease (n=60) were randomized to receive twice-daily SFC 50/250 via a Rotahaler and via Diskus each for two 10-day treatment periods (GlaxoSmithKline Protocol ASR114334). For FP and salmeterol, the in vitro aerodynamic particle size profiles were within±15% of Diskus for the fine particle mass (FPM) and emitted dose (ED) using the Andersen Cascade Impactor, and ED, mass median aerodynamic diameter, and geometric standard deviation using the New Generation Impactor (NGI). This was also the case for FP but not salmeterol for FPM and fine particle dose using the NGI. For the combined asthma and COPD subjects, the plasma AUC and Cmax for FP and salmeterol were higher for Rotahaler:Rotahaler/Diskus geometric mean ratios (90% confidence intervals) for FP AUC0-τ of 1.52 (1.37-1.67) and Cmax of 1.94 (1.75-2.10) and salmeterol AUC0-τ of 1.15 (1.09-1.21) and Cmax of 1.56 (1.42-1.67). Corresponding values for the primary pharmacodynamic endpoint, weighted mean (0-12 hr) serum cortisol, were 0.928 (0.886-0.971). Inhaled FP/salmeterol via both inhalers was well-tolerated. One serious adverse event, considered possibly related to study medication, resulted in subject withdrawal from the study. The in vitro tests and systemic pharmacodynamic endpoints revealed no major differences between the two inhalers, but lacked predictive power and sensitivity to guide in vivo drug delivery performance and systemic exposure. Based on pharmacokinetic endpoints, the inhalers were not considered bioequivalent in terms of systemic exposure. Further studies to refine the Rotahaler performance are ongoing.

A randomised cross-over trial investigating the ease of use and preference of two dry powder inhalers in patients with asthma or chronic obstructive pulmonary disease

Objectives: The objective of this randomised, cross-over study was to compare a new single-dose dry powder inhaler (Elpenhaler (EH)), with a widely used, multi-dose dry powder inhaler (Diskus (DK)) on critical errors, patient preference, and satisfaction with the inhalers.Methods: First, patients read the instructions of one device, followed by a first inhalation attempt. Inhalation errors were assessed and if mistakes were made, correct inhaler use was demonstrated. Then patients had to demonstrate again and mistakes were registered. This was repeated up to four times. After completing the first device, the same procedure was started with the second inhaler. Primary outcome was the percentage of patients making at least one critical error after reading the insert. Secondary outcomes were inhaler preference and satisfaction with the inhalers.Results: After reading the insert, 19 of 113 patients (17%) made at least one critical error with DK and 40 (35%) with EH (p = 0.001); 73% preferred the DK and 27% the EH (p < 0.001). The mean overall satisfaction score (1 = very satisfied; 5 = very dissatisfied) for DK was 1.59 and for EH 2.48 (p < 0.001).Conclusion: With DK fewer errors were made, more patients preferred DK over EH and patients were more satisfied with DK. This may enable DK to improve treatment outcomes more than EH.

Preference, satisfaction and errors with two dry powder inhalers in patients with COPD

Objective: To assess preference, satisfaction and critical errors with a novel, breath-actuated, multi-dose dry powder inhaler (DPI; Genuair®/Pressair™), versus a widely used, single-dose DPI (HandiHaler®) in patients with moderate-to-severe chronic obstructive pulmonary disease.Methods: In this randomised, open-label, multicentre, cross-over study, patients (aged ≥ 40 years) inhaled placebo once daily through both inhalers for 2 weeks in addition to current medication. The primary end point was percentage of patients who preferred Genuair to HandiHaler. Overall patient satisfaction (5-point scale: 1 = very dissatisfied; 5 = very satisfied), critical errors and willingness to continue using each inhaler (0 = not willing; 100 = definitely willing) were assessed.Results: Of 130 patients randomised, 105 were included in the intent-to-treat population (71.4% male; mean age 65.7 years). After 2 weeks, significantly more patients preferred Genuair than HandiHaler (79.1 vs 20.9%; p < 0.0001). Overall satisfaction scores (4.6 vs 3.8; p < 0.0001) and willingness to continue use scores (84.0 vs 62.5; p < 0.0001) were significantly higher with Genuair versus HandiHaler. Significantly fewer patients made ≥ 1 critical error with Genuair only compared with HandiHaler only (2.9 vs 19.0%; p < 0.0001).Conclusion: After 2 weeks' practice, patients preferred and were more willing to continue using Genuair than HandiHaler. Genuair was associated with higher patient satisfaction and fewer critical errors than HandiHaler.

Aclidinium Bromide Twice Daily for the Treatment of Chronic Obstructive Pulmonary Disease: A Review

The inhaled, long-acting muscarinic antagonist, aclidinium bromide, was indicated in July 2012 in Europe and the USA for the maintenance of bronchodilator treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults. Although initially investigated as a once-daily agent, a lower than expected improvement in trough forced expiratory volume over 1 s prompted re-evaluation as a twice-daily (b.i.d.) regimen. The dose approved for use in Europe, 400 μg b.i.d., achieved statistically significant improvements in lung function, reductions in breathlessness, and improved health-related quality of life (HRQoL) for up to 24 weeks of treatment in the pivotal phase 3 trials (AClidinium in Chronic Obstructive Respiratory Disease I [ACCORD COPD I] [12 weeks] and Aclidinium To Treat Airway obstruction In COPD patieNts [ATTAIN] [24 weeks]). These improvements were sustained during maintenance therapy of up to 52 weeks. Pooled data from the ATTAIN and ACCORD studies (both included a placebo arm) showed that exacerbation frequency was significantly reduced, although neither study was prospectively designed to evaluate this endpoint. Pharmacological and preclinical studies demonstrated the low systemic bioavailability of aclidinium and the low propensity to induce cardiac arrhythmias. The good tolerability of aclidinium was confirmed in the phase 3 program up to 52 weeks of treatment. The adverse event (AE) profile of the approved dose, 400 μg b.i.d., was similar to that of placebo, with a low incidence of anticholinergic and cardiac AEs. Aclidinium is delivered via the Genuair(®) multidose dry powder inhaler (Almirall Sofotec GmBH, Bad Homburg, Germany). The device is simple to use with multiple feedback mechanisms ensuring consistent dose delivery. In summary, aclidinium 400 μg b.i.d. is effective for the treatment of patients with COPD, offering improvements in lung function, breathlessness, and HRQoL, with a good safety profile and a low incidence of anticholinergic and cardiac AEs.

Aclidinium bromide for the treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is characterized by poorly reversible airflow obstruction. Long-acting bronchodilators improve lung function and relieve dyspnea. Aclidinium bromide is a novel long-acting antimuscarinic bronchodilator; Phase III clinical trials have demonstrated that administration of this drug twice per day improves lung function, dyspnea and health-related quality of life. Aclidinium bromide is delivered using the Genuair® device, which is an easy to use multidose dry powder inhaler. Aclidinium bromide is rapidly metabolized in the plasma, so there is low systemic exposure that minimizes the anticholinergic side effects. This new long-acting bronchodilator provides effective bronchodilation with minimal side effects.

The potential for aclidinium bromide, a new anticholinergic, in the management of chronic obstructive pulmonary disease

Long-acting muscarinic antagonists (LAMAs) play a central role in the management of chronic obstructive pulmonary disease (COPD). Previously, only one LAMA (tiotropium) was available for the treatment of COPD, necessitating the development of other therapeutic options due to the heterogeneity of COPD and patient responses to treatment. This article reviews the COPD management potential of aclidinium bromide, a LAMA administered twice daily (BID) by a multidose dry powder inhaler that is indicated for maintenance treatment of COPD. Aclidinium possesses kinetic selectivity for the M(3) versus M(2) receptor and is rapidly hydrolyzed in plasma to two major inactive metabolites, resulting in a low and transient systemic exposure and minimizing the potential for systemic side effects. A pharmacokinetic study with multiple doses of twice-daily aclidinium demonstrated the short half-life of aclidinium in plasma, suggesting that a steady state may be reached as early as the second day postdose. In a phase II study, twice-daily aclidinium 400 µg provided 24-hour bronchodilation, with significant improvements versus tiotropium during the second half of the day. In two phase III studies (ACCORD I and ATTAIN), both aclidinium 200 µg and 400 µg BID provided statistically significant improvements in trough forced expiratory volume in 1 second (FEV(1)) and other related lung function measurements. Improvements in peak FEV(1) on day 1 were comparable to those at study end, demonstrating that aclidinium provides maximal bronchodilation after the first dose that is maintained over time. Health status was significantly improved and dyspnea, nighttime and morning symptoms of COPD were likewise significantly reduced with aclidinium. Numerically greater improvements in efficacy were observed with the 400 µg dose compared with the lower dose, with similar safety profiles between the two doses and a low incidence of anticholinergic side effects. The approved therapeutic dose of aclidinium 400 µg BID is thus an effective new treatment option for patients with COPD.

Comparative Study of Patients in Correct Usage of and Preference for the Swinghaler and Turbuhaler Multidose Inhalers

Objective. Current dry powder inhalers (DPIs), introduced to overcome problems associated with pressurized metered dose inhalers (pMDIs), possess not only difficulties originating from their designs but also other barriers that prevent their correct usage. The authors of this study investigated the ease and correctness of use of Swinghaler, a new device in the form of multidose DPI, as well as the preference of the study participants for either a Swinghaler or a Turbuhaler. Methods. A total of 260 patients from Korea, China, Indonesia, the Philippines, Taiwan, and Thailand were prospectively recruited. Patients who had stable asthma, were more than 12 years old, had no experience with DPIs, and provided informed consents were included, whereas those with limited physical or intellectual ability and prior experience with any DPIs were excluded. Results. There were no group or time effects between the patients who were assigned to use a Swinghaler or a Turbuhaler first. Forty-one (16.1%) participants correctly performed the inhalation maneuver with a Swinghaler, whereas 28 (10.9%) did so with a Turbuhaler; the difference was not statistically significant. The overall assessment on the precise use of the devices indicated that there were no differences between Swinghaler and Turbuhaler usage. Comparing the preference scales between the two devices, the participants gave higher scores to the Swinghaler for all assessment items and were more satisfied with the Swinghaler compared with the Turbuhaler (78.5% vs. 55.0%, p < .001). Conclusions. The participants showed no difference in their ability to correctly use a Swinghaler when compared with a Turbuhaler and preferred the Swinghaler. These results suggest that the Swinghaler may be an effective and valuable tool for the management of airway diseases.