Efficacy and safety of indacaterol/glycopyrronium in Japanese patients with COPD: a subgroup analysis from the SHINE study

Abstract

BackgroundCOPD-related deaths are increasing in Japan, with ~5.3 million people at risk.MethodsThe SHINE was a 26-week, multicenter, randomized, double-blind, parallel-group study that evaluated safety and efficacy of indacaterol (IND)/glycopyrronium (GLY) 110/50 μg once daily (od) compared with GLY 50 μg od, IND 150 μg od, open-label tiotropium (TIO) 18 μg od, and placebo. The primary end point was trough forced expiratory volume in 1 second (FEV1) at Week 26. Other key end points included peak FEV1, area under the curve for FEV1 from 5 minutes to 4 hours (FEV1 AUC5 min–4 h), Transition Dyspnea Index focal score, St George’s Respiratory Questionnaire total score, and safety. Here, we present efficacy and safety of IND/GLY in the Japanese subgroup.ResultsOf 2,144 patients from the SHINE study, 182 (8.5%) were Japanese and randomized to IND/GLY (n=42), IND (n=41), GLY (n=40), TIO (n=40), or placebo (n=19). Improvement in trough FEV1 from baseline was 190 mL with IND/GLY and treatment differences versus IND (90 mL), GLY (100 mL), TIO (90 mL), and placebo (280 mL) along with a rapid onset of action at Week 26. IND/GLY showed an improvement in FEV1 AUC5 min–4 h versus all comparators (all P<0.05). All the treatments were well tolerated and showed comparable effect on Transition Dyspnea Index focal score and St George’s Respiratory Questionnaire total score. The effect of IND/GLY in the Japanese subgroup was consistent to overall SHINE study population.ConclusionIND/GLY demonstrated superior efficacy and comparable safety compared with its monocomponents, open-label TIO, and placebo and may be used as a treatment option for the management of moderate-to-severe COPD in Japanese patients.

<p>Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD: A Subgroup Analysis of the KRONOS Study</p>

“…Indeed, the small sample size and the relatively low number of exacerbation events in Japanese patients resulted in an estimate with high variability, and thus these findings should be interpreted with caution. The slightly lower overall rate of exacerbations in Japanese patients compared to the global population is consistent with other Japanese and Asian subgroup analyses in COPD, 9,10,22 as well as the fact that 80% of the Japanese population had no history of exacerbation in the previous year. The reduction in exacerbations observed with ICS-containing therapies compared to GFF MDI suggests that many symptomatic patients in Japan could benefit from the addition of an ICS to their treatment regimen (regardless of exacerbation history), as only 31.5% were receiving ICS therapy at study entry (compared to 71.8% of the global population).…”

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

“…No new or unexpected safety signals were observed in the study. Furthermore, a literature search to assess the potential risk of safety concerns in Japanese subjects resulting from an increased exposure for IND, GLY or MF did not reveal any safety concerns specific to the Japanese population following single or multiple dose administration of IND [ 18 , 30 ], GLY [ 31 ] or the IND/GLY combination [ 32 , 33 ] in COPD patients. The observed adverse events were expected in the patient population studied and were similar to those seen in studies conducted in the Caucasian population.…”

<p>Is the St. George’s Respiratory Questionnaire an Appropriate Measure of Symptom Severity and Activity Limitations for Clinical Trials in COPD? Analysis of Pooled Data from Five Randomized Clinical Trials</p>

“…Data from five clinical trials investigating a fixed-dose combination of a long-acting β2-agonist (indacaterol) and a long-acting muscarinic antagonist (glycopyrrolate) in COPD patients were used: FLIGHT-1, FLIGHT-2, 7 LANTERN, 8 SHINE 9 and SPARK. 10 The selection of the clinical trial data to be used was pre-specified before any analysis was performed and no change in selection was done during the analysis.…”