title: Efficacy and safety of combining olodaterol Respimat(®) and tiotropium HandiHaler(®) in patients with COPD: results of two randomized, double-blind, active-controlled studies.
abstract: BACKGROUND
  Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD). We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.
  
  
  METHODS
  Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat(®)) combined with tiotropium 18 μg once daily (via HandiHaler(®)) versus tiotropium 18 μg once daily (via HandiHaler(®)) combined with placebo (via Respimat(®)) in patients with moderate to severe COPD. Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials). A key secondary end point was health status by St George's Respiratory Questionnaire (SGRQ) total score (combined data set).
  
  
  RESULTS
  Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points. These effects translated to improvements in SGRQ total scores (treatment difference -1.85; P<0.0001). The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.
  
  
  CONCLUSIONS
  These studies demonstrated that olodaterol (Respimat(®)) and tiotropium (HandiHaler(®)) provided bronchodilatory effects above tiotropium alone in patients with COPD. In general, both treatments were well tolerated.
authors.affiliation: Saint Francis Hospital and Medical Center, Hartford, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: ZuWallack
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Allen
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Gemzel
authors.initials: G
authors.lastname: Hernandez
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Naitee
authors.initials: N
authors.lastname: Ting
authors.affiliation: Morgantown Pulmonary Associates, Morgantown, WV, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Abrahams
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004867:Equipment Design; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014481:United States
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D012602:Scopolamine Derivatives; C549647:olodaterol; D000069447:Tiotropium Bromide
keywords: bronchodilator; long-acting beta2-agonist; long-acting muscarinic antagonist; olodaterol Respimat®; tiotropium HandiHaler®