Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.

Objective: To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19).

Methods: In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured.

Long-term safety and efficacy of olopatadine-mometasone combination nasal spray in patients with perennial allergic rhinitis.

Safety and efficacy of GSP301 nasal spray, an investigational fixed-dose combination of olopatadine hydrochloride and mometasone furoate, was established in three large, 2-week seasonal allergic rhinitis studies. To evaluate long-term (52 weeks) safety and efficacy of GSP301 in patients with perennial allergic rhinitis (PAR). In this randomized, double-blind, parallel-group study, 601 patients (ages ≥ 12 years) with PAR were randomized 4:1:1 to twice-daily GSP301 (olopatadine 665 μg and mometasone 25 μg [pH 3.

Olopatadine-mometasone combination nasal spray: Evaluation of efficacy and safety in patients with seasonal allergic rhinitis.

GSP301 is an investigational fixed-dose combination nasal spray that contains the antihistamine, olopatadine hydrochloride (HCl), and the corticosteroid, mometasone furoate. To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). In this double-blind, randomized, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to intranasal GSP301 (olopatadine 665 μg and mometasone 25 μg), olopatadine HCl (665 μg), mometasone furoate (25 μg), or placebo for 14 days of twice-daily treatment.

Efficacy and safety of olopatadine-mometasone combination nasal spray for the treatment of seasonal allergic rhinitis.

Background: GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid).

Objective: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR).

Methods: In this double-blind study, eligible patients (≥12 years of age) with SAR were randomized 1:1:1:1 to twice-daily GSP301 (665 μg of olopatadine and 25 μg of mometasone), olopatadine (665 μg), mometasone (25 μg), or placebo for 14 days.

The pharmacokinetics, safety, and tolerability of single, high-strength doses of fluticasone propionate and fluticasone propionate/salmeterol delivered via a novel multidose dry powder inhaler in adolescents and adults with persistent asthma.

Objective: Characterize fluticasone propionate (Fp) and combination fluticasone propionate and salmeterol (FS) pharmacokinetic and safety profiles, delivered via a novel, inhalation-driven, multidose dry powder inhaler (MDPI).

Methods: This multicenter, open-label, four-period crossover, single-dose study randomized patients aged ≥12 years with persistent asthma to Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, Fp dry powder inhaler (DPI) 500 mcg (250 mcg × 2 inhalations), or FS DPI 500/50 mcg.

Randomized, double-blind trial evaluating the efficacy and safety of fluticasone propionate and fluticasone propionate/salmeterol delivered via multidose dry powder inhalers in patients with persistent asthma aged 12 years and older.

Objective: To assess the efficacy and safety of fluticasone propionate (Fp) and Fp/salmeterol (FS) administered via a novel multidose dry powder inhaler (MDPI) that is easy to use correctly in asthma patients.

Methods: This phase-3, multicenter, double-blind, parallel-group study evaluated asthmatic patients (≥12 years of age) previously treated with either low- or mid-dose inhaled corticosteroids (ICSs) or ICS/long-acting beta agonists. After a 14- to 21-day run-in, patients were randomized to Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI 50/12.

Fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers compared with placebo for persistent asthma.

Background: A novel, inhalation-driven, multidose dry powder inhaler (MDPI) has been developed, which allows for lower doses of fluticasone propionate (Fp) and Fp/salmeterol (FS) for the treatment of patients with asthma.

Objective: This phase III, multicenter, double-blind, parallel-group study (NCT02141854) evaluated the efficacy and safety of Fp MDPI and FS MDPI versus placebo MDPI.

Methods: Patients aged ≥12 years with persistent asthma who previously took an inhaled corticosteroid with or without a long-acting beta-agonist entered a 14- to 21-day run-in period, during which they received single-blind, low-dose Fp MDPI 50 μg (1 inhalation twice daily [b.

A 6-month safety and efficacy study of fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers in persistent asthma.

Background: A novel multidose dry powder inhaler (MDPI) that is breath actuated, easy, and intuitive to use has been developed for administering fluticasone propionate (Fp) and Fp/salmeterol (FS).

Objective: To assess the safety and efficacy of Fp MDPI versus Fp hydrofluoroalkane (HFA) and FS MDPI versus FS dry-powder inhaler (DPI).

Methods: This phase III, 26-week, open-label, active drug-controlled study enrolled subjects ≥12 years old with persistent asthma.

Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study.

Background: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.

Methods: In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.

Aclidinium improves exercise endurance, dyspnea, lung hyperinflation, and physical activity in patients with COPD: a randomized, placebo-controlled, crossover trial.

Background: This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung hyperinflation, and physical activity.

Methods: In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe airflow limitation received aclidinium 400 μg twice daily or placebo via Genuair®/Pressair(®a) for 3 weeks (2-week washout between treatment periods). The primary endpoint was change from baseline to Week 3 in endurance time, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate.

Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study.

Background: Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.

Methods: In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.

Characterisation and impact of reported and unreported exacerbations: results from ATTAIN.

The frequency and impact of exacerbations identified using healthcare resource utilisation (HCRU) or the EXAcerbations of Chronic pulmonary disease Tool (EXACT) were compared prospectively in a 24-week, phase III trial (ATTAIN). Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 μg, aclidinium 400 μg or placebo. All HCRU events were reported to physicians.

ACCORD COPD II: a randomized clinical trial to evaluate the 12-week efficacy and safety of twice-daily aclidinium bromide in chronic obstructive pulmonary disease patients.

Background And Objectives: Aclidinium bromide is a long-acting muscarinic antagonist approved for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). This 12-week phase III study evaluated efficacy and tolerability of aclidinium 200 or 400 μg in patients with moderate-to-severe COPD.

Methods: In this double-blind study, 544 patients with COPD were randomized to placebo or twice-daily aclidinium 200 or 400 μg administered by Genuair(®)/Pressair(®).

Long-term safety and efficacy of twice-daily aclidinium bromide in patients with COPD.

Background: Aclidinium is a novel, long-acting muscarinic antagonist indicated for maintenance treatment of COPD.

Methods: In this 52-week, parallel-group, double-blind study, patients with moderate-to-severe COPD were randomized (1:1) to receive aclidinium twice-daily (BID) 200 μg or 400 μg via a novel, dry powder inhaler (Genuair(®)/Pressair(®)) [Registered trademarks of Almirall, SA, Barcelona, Spain for use within the European Union, Iceland, Norway, and Switzerland as Genuair(®) and within the United States as Pressair(®)]. Safety, the primary objective, was assessed via adverse events (AEs), clinical laboratory tests, vital signs, and 12-lead electrocardiograms.

Efficacy and safety of aclidinium bromide compared with placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease: results from a 6-week, randomized, controlled Phase IIIb study.

Background: This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.

One-year extension study of ACCORD COPD I: safety and efficacy of two doses of twice-daily aclidinium bromide in patients with COPD.

This was a 52-week, double-blind, extension study in which COPD patients previously treated with twice-daily (BID) aclidinium bromide 200 μg or 400 μg during a 12-week lead-in study (ACCORD COPD I) continued the same treatment, while patients previously receiving placebo were rerandomized (1:1) to aclidinium 200 μg or 400 μg BID. The primary objective of this study was to evaluate the long-term safety and tolerability of aclidinium treatment. Efficacy outcomes included bronchodilation, health status, and rescue medication use.

A randomised, placebo- and active-controlled dose-finding study of aclidinium bromide administered twice a day in COPD patients.

This Phase IIb, double-blind, double-dummy, placebo- and active-comparator-controlled crossover study (ClinicalTrials.gov identifier: NCT01120093) assessed efficacy and safety of three doses of aclidinium bromide in patients with moderate to severe chronic obstructive pulmonary disease. Patients were randomised to one of five treatment sequences each consisting of twice-daily (BID) aclidinium 100 μg, 200 μg, 400 μg (via Genuair®*), formoterol 12 μg (via Aerolizer®) and matched placebo for 7 days, with a 5- to 9-day washout period.

Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study.

The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). In this 24-week, double-blind trial, patients were randomised to twice-daily aclidinium (200 μg or 400 μg) or placebo. The primary efficacy end-point was change in trough forced expiratory volume in 1 s (FEV(1)) at week 24.

Safety and pharmacokinetics of multiple doses of aclidinium bromide administered twice daily in healthy volunteers.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction and increased cholinergic tone. The global initiative for chronic obstructive lung disease (GOLD) guidelines recommend long-acting anticholinergics for COPD maintenance treatment. Aclidinium bromide is a novel, long-acting muscarinic antagonist developed for the treatment of COPD.

Efficacy and safety of a 12-week treatment with twice-daily aclidinium bromide in COPD patients (ACCORD COPD I).

Background: This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD.

Methods: In this 12-week, double-blind, multicenter trial, patients were randomized (1:1:1) to inhaled twice-daily aclidinium 200 μg, aclidinium 400 μg, or placebo. Primary and secondary endpoints were changes from baseline in trough FEV₁ and peak FEV₁ at Week 12, respectively.

Mass balance and metabolism of aclidinium bromide following intravenous administration of [¹⁴C]-aclidinium bromide in healthy subjects.

Aclidinium bromide is a novel, inhaled long-acting muscarinic antagonist with low systemic activity developed for the treatment of COPD. It is an ester compound rapidly hydrolysed in plasma into inactive alcohol and acid metabolites. In this Phase I, open-label study, the rates and routes of elimination of radioactivity following intravenous administration of [¹⁴C]-aclidinium bromide were determined.

Efficacy of aclidinium bromide 400 μg twice daily compared with placebo and tiotropium in patients with moderate to severe COPD.

Background: The efficacy and safety of aclidinium bromide bid, a novel, long-acting, muscarinic antagonist, was assessed in patients with moderate to severe COPD.

Methods: In this phase IIa randomized, double-blind, double-dummy, crossover trial, patients with moderate to severe COPD received aclidinium 400 μg bid, tiotropium 8 μg once daily, and placebo for 15 days, with a 9- to 15-day washout between treatment periods. Treatments were administered through the Genuair or HandiHaler dry powder inhalers.

Safety and tolerability of aclidinium administered intravenously and absolute bioavailability of inhaled aclidinium in healthy male participants.

Aclidinium bromide is a long-acting muscarinic antagonist in development for chronic obstructive pulmonary disease treatment. This 2-part, phase I study evaluated the safety and tolerability of single ascending intravenous (IV) doses of aclidinium to determine its maximum tolerated dose (MTD; part I) and its absolute bioavailability (part II). Healthy male participants (N = 24) were randomized (1:1) in each part: 3-period crossover, placebo-controlled, single-ascending, alternating IV doses of aclidinium (25-400 µg) in part I and 2-period crossover, single-alternating IV and inhaled doses of aclidinium (200 µg) in part II.