Analysis of Patient Characteristics and Peak Inspiratory Flow Rates in Three Phase 3 Trials of Nebulized Glycopyrrolate in Moderate to Very Severe COPD

Abstract

SESSION TITLE: COPD 3 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Successful use of dry powder inhalers requires adequate inspiratory flow; however, many COPD patients have reduced peak inspiratory flow rates (PIFR). Identifying patients with low PIFR may help with device selection; nebulizers rely on tidal breathing so are less affected by inspiratory flow. This post-hoc analysis investigated the relationship between baseline PIFR and patient characteristics in three Phase 3 trials of nebulized glycopyrrolate (GLY) administered via the eFlow® Closed System nebulizer (PARI Pharma, Germany) in moderate-to-very-severe COPD. METHODS: Data from two replicate 12-week, placebo-controlled trials of nebulized GLY were pooled. PIFR was measured using the ‘free-flow’ resistance setting on the In-Check DIAL. Data from a 48-week safety study of nebulized GLY vs tiotropium (TIO; Handihaler) were also analyzed. PIFR was measured using the ‘Handihaler’ resistance setting on the In-Check DIAL. Subjects were stratified by PIFR (<60 and ≥60 L/min) and analyzed by age, gender, height and weight, all previously shown to correlate with PIFR (Mahler et al. JAMPDD 2013;26:174-9). RESULTS: Data from 1291 subjects in the 12-week placebo-controlled studies were analyzed. At baseline, the forced expiratory volume in one second (FEV1) % predicted was 51.7%, and 31.1% of subjects were receiving long-acting β2-agonists (LABA). 331 (25.6%) subjects had PIFR <60 L/min and 960 (74.4%) PIFR ≥60 L/min. In both groups, median age was 63 years and 9.7% of subjects were ≥75 years old. The percentage of females was slightly higher in the <60 L/min group than the ≥60 L/min group (45.6% vs 43.4%). Median height (171 cm), and weight (81 kg), did not differ between PIFR groups. GLY improved lung function in subjects irrespective of PIFR and adverse event rates did not differ between groups. Data from 1072 subjects in the 48-week safety study were analyzed. At baseline, FEV1 % predicted was 51.3% and 42.3% of subjects were receiving LABA. 363 (33.9%) subjects had PIFR <60 L/min and 709 (66.1%) PIFR ≥60 L/min. Median age was 64 years and 63 years in the <60 L/min and ≥60 L/min groups, respectively. The percentage of subjects ≥75 years was higher in the <60 L/min group (11.3%) than in the ≥60 L/min group (8.7%). There was a greater percentage of females in the <60 L/min group (48.8%) than in the ≥60 L/min group (41.3%). Median height was 169 cm in the <60 L/min group and 170.1 cm in the ≥60 L/min group, and the corresponding weights were 80.7 kg and 82 kg. GLY and TIO improved lung function in subjects irrespective of PIFR and adverse event rates did not differ between groups. CONCLUSIONS: In the analysis using the resistance-free In-Check DIAL, PIFR was largely unaffected by age, gender, height and weight. In the analysis using the ‘Handihaler’ resistance setting, PIFR <60 L/min was associated with female gender, age ≥75 years, and, to a lesser extent, smaller body size. CLINICAL IMPLICATIONS: Certain patient characteristics may be related to PIFR, which could be useful to consider when selecting an appropriate inhalation device. Increasing the resistance on the In-Check DIAL may reveal correlations between patient characteristics and PIFR that are not observed on a resistance-free setting. DISCLOSURE: Donald Mahler: Consultant fee, speaker bureau, advisory committee, etc.: Sunovion Pharmaceuticals Inc., Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Barry Price: Employee: Sunovion Pharmaceuticals Inc. Robert Tosiello: Employee: Sunovion Pharmaceuticals Inc. Sanjay Sharma: Employee: Sunovion Pharmaceuticals Inc. Abstract describes analysis from Phase 3 trials of nebulized glycopyrrolate in COPD (not currently approved)