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Bronchodilator efficacy of 18 ?g once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial.

ABSTRACT: PURPOSE:To compare the bronchodilator efficacy of 18 ?g once-daily tiotropium inhalation administered via Discair® versus HandiHaler® in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS:Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation with Discair) or a reference group (n=29, inhalation with HandiHaler). The primary efficacy parameter was the average maximum change in forced expiratory volume in 1 second (FEV1, in L). Change in forced vital capacity (FVC, in L), %FEV1 and %FVC, the standardized area under the response-time curve (AUC) for the absolute change in FEV1 and FVC, time to onset and peak of response, and safety data were also evaluated. RESULTS:The test inhaler was non-inferior to the reference inhaler in terms of maximum change in FEV1 at 24 h (unadjusted change: 0.0017 L [95% confidence interval [CI]: -0.0777, 0.0812]; change adjusted for time to reach maximum change in FEV1 and smoking in pack-years: 0.0116 L [95% CI: -0.0699, 0.0931]), based on a non-inferiority margin of 0.100 L. There were also no significant differences between the two groups in maximum change in FVC value from baseline (0.3417 L vs 0.4438 L, P=0.113), percent change from baseline (22.235 vs 20.783 for FEV1, P=0.662; 16.719 vs 20.337 for FVC, P=0.257), and AUC0-24 h (2.949 vs 2.833 L for FEV1, P=0.891; 2.897 vs 4.729 L for FVC, P=0.178). There were no adverse events, serious adverse events, or deaths. CONCLUSION:Our findings show that the Discair was non-inferior to the HandiHaler. More specifically, these devices had similar clinical efficacy in terms of time-dependent response over 24 h for patients with moderate-to-severe COPD.

SUBMITTER: Yildiz P

PROVIDER: S-EPMC5125983 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Bronchodilator efficacy of 18 μg once-daily tiotropium inhalation via Discair<sup>®</sup> versus HandiHaler<sup>®</sup> in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial.

Yildiz Pinar P Bayraktaroglu Mesut M Gorgun Didem D Secik Funda F

International journal of chronic obstructive pulmonary disease 20161122

<h4>Purpose</h4>To compare the bronchodilator efficacy of 18 μg once-daily tiotropium inhalation administered via Discair<sup>®</sup> versus HandiHaler<sup>®</sup> in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD).<h4>Patients and methods</h4>Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation ...[more]

PMID: 27920513

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Project description:IntroductionTiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler(®) (18 μg once daily) or Respimat(®) Soft Mist™ inhaler (5 μg once daily). The recent TIOtropium Safety and Performance In Respimat(®) (TIOSPIR™) study demonstrated that both exhibit similar safety profiles. This analysis provides an updated comprehensive safety evaluation of tiotropium(®) using data from placebo-controlled HandiHaler(®) and Respimat(®) trials.MethodsPooled analysis of adverse event (AE) data from tiotropium HandiHaler(®) 18 μg and Respimat(®) 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks). Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler(®) and Respimat(®) trials, both together and separately.ResultsIn the 28 HandiHaler(®) and 7 Respimat(®) trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler(®); 2,440 with Respimat(®)) patient-years of tiotropium exposure. Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted). The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler(®) and Respimat(®) pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]). The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group. Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium. Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.ConclusionThis analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler(®) or Respimat(®) (overall and separately) in patients with COPD.

Project description:Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting ?2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat(®) and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler(®) for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.

Project description:Bronchodilation with muscarinic antagonists, β2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using "duration and lung selectivity-by-design." This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.

Project description:BackgroundThis study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β2-agonist (LABA).Methods285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209).Primary objectiveto describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV1) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.ResultsAt Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.ConclusionsThe long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.Trial registrationClinicalTrials.gov NCT01340209.

Dataset Information

Bronchodilator efficacy of 18 ?g once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial.

Publications

Bronchodilator efficacy of 18 μg once-daily tiotropium inhalation via Discair<sup>®</sup> versus HandiHaler<sup>®</sup> in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial.

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