Science and Research

ACTIVATE: the effect of aclidinium/formoterol on hyperinflation, exercise capacity, and physical activity in patients with COPD

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.
Publication details
DOI: 10.2147/COPD.S143488
Journal: International journal of chronic obstructive pulmonary disease
Pages: 2545-2558 
Work Type: Original
Location: ARCN
Disease Area: COPD
Partner / Member: Ghd
Access-Number: 28883722
See publication on PubMed

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