ABSTRACT
BACKGROUND: Symptoms of chronic obstructive pulmonary disease may vary throughout the day and it is important that therapeutic approaches provide 24-h symptom control. We report the results of two phase IIIb crossover studies, PT003011 and PT003012, investigating the 24-h lung function profile of GFF MDI (glycopyrrolate/formoterol fumarate 18/9.6 µg delivered using innovative co-suspension delivery technology) administered twice daily. METHODS: Patients with moderate-to-very severe chronic obstructive pulmonary disease received 4 weeks' treatment with each of GFF MDI, placebo MDI, and open-label tiotropium (PT003011 only). Lung function was assessed over 24 h on day 29 of each treatment period. The primary outcome was forced expiratory volume in 1 second area under the curve from 0 to 24 h (FEV1AUC0-24). Other outcomes included change from baseline in average daily rescue medication use over the treatment period. In addition, we conducted a post-hoc analysis of data pooled from both studies to further characterize the effect of GFF MDI on inspiratory capacity. RESULTS: GFF MDI treatment significantly increased FEV1AUC0-24 versus placebo in studies PT003011 (n = 75) and PT003012 (n = 35) on day 29 (both studies p < 0.0001), with similar improvements in FEV1AUC versus placebo for hours 0-12 and 12-24. In PT003011, improvements with GFF MDI versus tiotropium in FEV1AUC were greater during hours 12-24 compared to 0-12 h. GFF MDI treatment also resulted in a significant reduction in rescue medication use versus placebo (-0.84 [p<0.0001] and -1.11 [p=0.0054] puffs/day in PT003011 and PT003012, respectively), and versus tiotropium in PT003011 (-0.44 [p=0.017] puffs/day). A post-hoc pooled analysis showed patients treated with GFF MDI were more likely to achieve a >15% increase from baseline in inspiratory capacity than patients treated with placebo or tiotropium (72.1%, 19.0% and 47.0% of patients, respectively after the evening dose on day 29). There were no significant safety/tolerability findings. CONCLUSIONS: GFF MDI significantly improved 24-h lung function versus placebo in patients with moderate-to-very severe chronic obstructive pulmonary disease, with similar benefits in the second 12-h period compared to the first, supporting twice-daily dosing of GFF MDI. TRIAL REGISTRATION: Pearl Therapeutics, Inc.; www.clinicaltrials.gov ; NCT02347072 and NCT02347085 . Registered 21 January 2015.
Subject(s)
Bronchodilator Agents/administration & dosage , Drug Delivery Systems/methods , Formoterol Fumarate/administration & dosage , Glycopyrrolate/administration & dosage , Inspiratory Capacity/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Aged , Cross-Over Studies , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Inspiratory Capacity/physiology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Time FactorsABSTRACT
PURPOSE: To provide information on the efficacy and safety of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler 230/42mcg (FSC MDI) and its comparable dose of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg (FSC DISKUS) in patients with COPD. METHODS: This multicenter, randomized, double-blind, 12 week study was designed to evaluate FSC MDI treatment responses as compared with FSC DISKUS. The primary comparison of interest was non-inferiority between the FSC MDI treatment group and the FSC DISKUS treatment group assessed in terms of 2-hour post-dose FEV(1) change from baseline at endpoint. The non-inferiority criterion bound was 75mL (lower confidence limit of -75mL). INCLUSION CRITERIA: Male or female aged ≥ 40, post-bronchodilator FEV(1) ≤ 70% predicted normal, FEV(1)/FVC ≤ 70% and ≥ 10 pack years smoking history. Adverse events were recorded by patients throughout the study on daily diary cards. Adverse events were collected in eCRFs at all clinic visits and during a final follow-up phone call. RESULTS: Patients (N=247) were randomized to FSC MDI (FEV(1)% 49.3 ± 12.3, FEV(1)/FVC 50.5 ± 10.0) and FSC DISKUS (FEV(1)% 48.4 ± 11.0, FEV(1)/FVC 50.3 ± 10.3). From an ANCOVA model the least squares (LS) mean difference (FSC MDI- FSC DISKUS) for the 2-hour post dose FEV(1) at endpoint was -2.0mL (95% CI -64mL, 59mL). Pre-dose FEV(1), FVC, PEF, and albuterol use were also similar between the two formulations. The most common adverse events (AE) during treatment were headache (8% and 6% of patients), nasopharyngitis (4% and 6%), cough (3% and 4%), and sinusitis (2% and 5%) for FSC MDI and FSC DISKUS, respectively. Pneumonia was recorded as an AE for 2 (2%) patients in the FSC DISKUS arm. CONCLUSION: This is the first study to demonstrate that FSC MDI has a similar efficacy and safety profile to FSC DISKUS in COPD patients.
