SESSION TITLE: COPD LAMA/LABA
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 27, 2014 at 01:30 PM - 02:30 PM
PURPOSE: Studies with SUN-101 (Glycopyrrolate Inhalation Solution) delivered via a novel nebulizer have evaluated once-daily dosing in COPD subjects. This study evaluated the efficacy and safety of twice daily treatment.
METHODS: This was a double‑blind, randomized, placebo‑controlled, parallel group study. Subjects meeting inclusion criteria (35-70 years old with COPD, baseline FEV1 ≥ 30% and ≤70% of predicted and ≥10 pack‑year smoking history) were randomized to one of four doses of SUN-101 (12.5 mcg, n=55; 25 mcg, n=54; 50 mcg n=57; 100 mcg n=59) or placebo (n=57) BID for 28 days. Subjects receiving LABA or LAMA therapy had their treatment replaced with albuterol MDI as “rescue therapy”. Inhaled corticosteroids and roflumilast were continued throughout the study. The primary assessment was change from baseline in morning trough FEV1 after 28 days of treatment.
RESULTS: All doses were associated with rapid onset of bronchodilation which persisted throughout the 24 hour dosing interval. Improvements in trough FEV1 after 28 days of treatment (placebo adjusted LS [95% CI]) were 116.8 mL(36.9, 196.6), 128.4 mL (47.9, 208.9), 146.2 mL (66.7, 225.7) and 177.0 mL (99.2, 254.8) for the 12.5, 25, 50 and 100 mcg doses respectively (p<0.05 vs placebo). Improvements were seen in FEV1 AUC0-12 with changes from baseline (mean [95% CI]) of 135.7 (70.9, 200.5) mL, 163.2 (98.2, 228.3) mL, 105.4 (41.5, 169.4) mL and 183.1 (119.9, 246.2) mL for the 12.5 mcg, 25 mcg. 50 mcg and 100 mcg groups respectively (p<0.05 vs placebo). The most commonly reported adverse events were COPD exacerbations and headache, reported by 3.2% and 2.8% of the population respectively.
CONCLUSIONS: Twice daily treatment with SUN-101 produced dose-dependent increases in trough FEV1 and FEV1 AUC0-12. Although all doses were associated with a mean increase above the MCID of 100 mL, the lower bound of the 95% confidence intervals suggest that lower doses (e.g., 12.5 mcg bid) may be less consistently beneficial. FEV1 AUC0-12 may be a useful endpoint for the assessment of twice daily bronchodilators. Additional work is required to further define the appropriate dose regimen for SUN-101.
CLINICAL IMPLICATIONS: Nebulized glycopyrrolate delivered via the eFlow may represent an additional treatment option for patients with moderate to severe COPD.
DISCLOSURE: Edward Kerwin: Grant monies (from industry related sources): Grants received from Sunovion Pharmaceuticals Inc. Alistair Wheeler: Employee: Employee of Sunovion Pharmaceuticals Inc. Kendyl Schaefer: Employee: Employee of Sunovion Pharmaceuticals Inc. Raymond Claus: Employee: Employee of Sunovion Pharmaceuticals Inc. Ahmet Tutuncu: Other: Clinical Consultant to Sunovion Pharmaceuticals. Nicola Hanania: Grant monies (from industry related sources): Grants received from Sunovion Pharmaceuticals Inc.
Nebulized glycopyrrolate is not approved for the treatment of COPD in any country.