Pooled Safety Analysis of Once-Daily Tiotropium and Olodaterol Fixed-Dose Combination via the Respimat in Patients With Chronic Obstructive Pulmonary Disease: Two 1-Year Studies.

SESSION TITLE: COPD Treatment PostersSESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: Tiotropium, a long-acting muscarinic antagonist, has recently been assessed in fixed-dose combination (FDC) with olodaterol, a once-daily, long-acting β2-agonist, for treatment of chronic obstructive pulmonary disease (COPD). We present pooled safety data from two pivotal, replicate, Phase III studies assessing efficacy and safety of FDCs of tiotropium and olodaterol(T+O) delivered via Respimat® inhaler in patients with GOLD stage 2-4 COPD.METHODS: In these 52-week, double-blind, parallel-group studies, patients were randomized to five arms: once-daily olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, T+O 2.5/5 µg, T+O 5/5 µg. Key inclusion criteria included: age ≥40 years, diagnosis of COPD, smoking history >10 pack-years. Patients with a history of asthma or significant disease other than COPD were excluded; however, patients with stable cardiovascular co-morbidities were included. Adverse events (AEs) were reported throughout.RESULTS: In total, 5162 patients were randomized and treated. AEs, serious AEs, and fatal AEs were generally balanced across treatment groups. AE incidence was 76.6% (olodaterol 5 µg), 73.4% (tiotropium 2.5 µg), 73.3% (tiotropium 5 µg), 74.7% (T+O 2.5/5 µg), and 74.0% (T+O 5/5 µg). The most frequently reported AEs were respiratory events (according to MedDRA System Organ Class), including COPD exacerbations (34.1-35.6% with monotherapies versus 29.2-32.3% with FDCs) and dyspnea (3.7-4.9% with monotherapies versus 3.9-4.2% with FDCs). Frequencies of cardiac disorders were generally balanced across groups (4.5-5.8%), while respiratory events were more frequent among patients treated with monotherapies (42.7-45.3%) than FDCs (38.2-39.4%). Most events were mild to moderate in severity and not considered related to study treatment. Groups receiving T+O FDCs reported fewer rescue medication usages compared to groups receiving single components.CONCLUSIONS: T+O FDCs were well tolerated with no increase in incidence of AEs compared to individual components.CLINICAL IMPLICATIONS: The equivalent tolerability of T+O FDCs compared to the monotherapies suggests there are no safety signals with the combined therapy in patients with COPD. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.DISCLOSURE: Roland Buhl: Consultant fee, speaker bureau, advisory committee, etc.: Astra Zeneca, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Chiesi, Consultant fee, speaker bureau, advisory committee, etc.: Grifols, Consultant fee, speaker bureau, advisory committee, etc.: GSK, Consultant fee, speaker bureau, advisory committee, etc.: Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Roche, Consultant fee, speaker bureau, advisory committee, etc.: Takeda Roger Abrahams: Grant monies (from industry related sources): Clinical Research Grant from Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim steering committe Leif Bjermer: Fiduciary position (of any organization, association, society, etc, other than ACCP: Principle Investigator, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Advisory Board Eric Derom: Consultant fee, speaker bureau, advisory committee, etc.: Consultant - Boehringer Ingelheim & Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Speaker - - Boehringer Ingelheim and GSK, Consultant fee, speaker bureau, advisory committee, etc.: Advisory Board - Chiesi & Astra Zeneca Matjaz Flezar: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim Advisory Board, Grant monies (from industry related sources): Principle Investigator in Boehringer Ingelheim Clinical Trials Jacques Hébert: Other: Board Memeber: Novartis, King (Pfizer), Palladin, Merck, CSL Behring, Other: Centre de Recherche involved with clinical trials sponsored by Boehringer Ingelheim, Merck, Novartis, Circassia CSL Behring Lars Groenke: Employee: Boehringer Ingelheim Kay Tetzlaff: Employee: Boehringer Ingelheim Lawrence Korducki: Employee: Boehringer Ingelheim Holger Huisman: Employee: Boehringer Ingelheim Stella Waitere-Wijker: Employee: Boehringer Ingelheim Lorcan McGarvey: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fees for adjudication activity on COPD clinical trials The following authors have nothing to disclose: Anthony VealeThis presentation will describe the Phase III study investigating the safety and efficacy of a tiotropium plus olodaterol fixed dose combination therapy for the treatment of COPD.