The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 mug twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD. Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair/Pressair((R)) dry powder inhaler for 8 weeks. From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals). The primary end point was trough functional residual capacity (FRC) at Week 4. Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI). Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise. After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690). However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P<0.0001). AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 (P<0.01 and P<0.0001, respectively) and Week 8 (P<0.05 and P<0.0001, respectively). AB/FF achieved higher step counts (P<0.01) with fewer inactive patients (P<0.0001) at Week 4 versus placebo. Following BI, AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo. AB/FF 400/12 mug demonstrated improvements in lung hyperinflation, exercise capacity, and physical activity versus placebo that were maintained following the addition of BI. A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF.
- Watz, H.
- Troosters, T.
- Beeh, K. M.
- Garcia-Aymerich, J.
- Paggiaro, P.
- Molins, E.
- Notari, M.
- Zapata, A.
- Jarreta, D.
- Garcia Gil, E.
Keywords
- Adrenergic beta-2 Receptor Agonists/adverse effects/*therapeutic use
- Aged
- Bronchodilator Agents/adverse effects/*therapeutic use
- Canada
- Double-Blind Method
- Drug Combinations
- Europe
- *Exercise
- Exercise Tolerance/*drug effects
- Female
- Formoterol Fumarate/adverse effects/*therapeutic use
- Functional Residual Capacity
- Humans
- Inspiratory Capacity
- Lung/*drug effects/physiopathology
- Male
- Middle Aged
- Muscarinic Antagonists/adverse effects/*therapeutic use
- Pulmonary Disease, Chronic Obstructive/diagnosis/*drug therapy/physiopathology
- Recovery of Function
- Time Factors
- Treatment Outcome
- Tropanes/adverse effects/*therapeutic use
- *Copd
- *aclidinium
- *exercise capacity
- *formoterol
- *hyperinflation
- *physical activity
- travel support to attend scientific congresses from Almirall, AstraZeneca,
- Berlin-Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and
- Takeda. His institution received investigator fees for participation in clinical
- trials from Almirall, AstraZeneca, Bayer Health Care, Berlin-Chemie, Boehringer
- Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi Aventis, Roche, and Takeda.
- Thierry Troosters has received grants from the Innovative Medicines Initiative
- Joint Undertaking and speaker fees from Boehringer Ingelheim, AstraZeneca, and
- GlaxoSmithKline. Kai M Beeh's institution has received compensation for
- organizing or participating in advisory boards (from Almirall Hermal, Cytos,
- Chiesi, Boehringer Ingelheim, AstraZeneca, Mundipharma, Novartis, and Teva), has
- participated in scientific meetings or courses (supported by Almirall Hermal,
- AstraZeneca, Boehringer Ingelheim, Mundipharma, Novartis, Pfizer, and Teva) in
- the past 3 years, has received consulting fees (from Ablynx, Apellis
- Pharmaceuticals, Sterna GmbH, Chiesi, and Cytos), and has received compensation
- for the design, performance, or participation in single or multicenter clinical
- trials in the past 3 years (from Almirall, AstraZeneca, Boehringer Ingelheim,
- GlaxoSmith-Kline, Infinity, Mundipharma, Novartis, Pfizer, Revotar
- Biopharmaceuticals, Sterna GmbH, Teva, and Zentiva). Judith Garcia-Aymerich's
- institution has received consulting and lecture fees from AstraZeneca, and
- lecture fees from Esteve. Pierluigi Paggiaro is on the AstraZeneca, Boehringer
- Ingelheim, Chiesi, GlaxoSmithKline, and Novartis boards and has received lecture
- fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Laboratori
- Guidotti, Menarini, Mundipharma, Novartis, Sanofi, and Teva. Eduard Molins, Diana
- Jarreta, and Esther Garcia Gil are employees of AstraZeneca PLC, Barcelona,
- Spain. Massimo Notari is an employee of A. Menarini Farmaceutica Internazionale
- S.R.L., Firenze, Italy. Antonio Zapata is an employee of Laboratorios Menarini,
- S.A., Badalona, Spain. The authors report no other conflicts of interest in this
- work.