formoterol dose ranging study (achieve duaklir usa phase iib)

Conditions: Chronic Obstructive Pulmonary Disease - COPD

Summary: to assess the bronchodilation of three doses of formoterol fumarate (6 μg, 12 μg and 24 μg) twice daily (bid) administered via pressair® compared to placebo and to open-label nebulized formoterol fumarate (20 μg and 40 μg).

this is a prospective, randomized, double-blind, 5-period incomplete unbalanced crossover, placebo and active comparator (open-label) controlled, multicenter clinical trial to assess the efficacy and safety of three doses of formoterol fumarate (6 μg, 12 μg and 24 μg) bid administered via pressair® compared to placebo and to open-label formoterol fumarate (20 μg bid and 40 μg single dose) administered as an inhalation solution via a standard jet nebulizer (with a mouthpiece) connected to an air compressor (perforomist® inhalation solution). the drug product is an inhalation powder comprising of micronized aclidinium bromide and micronized formoterol fumarate with α-lactose monohydrate as the carrier, presented in a breathactuated device-metered dry-powder inhaler (dpi). it has been approved under the trademarks of genuair® and/or pressair® in some territories.

Eligibility criteria:
inclusion criteria: * adult male or non-pregnant, non-lactating female patients aged ≥40. * patients with a diagnosis of copd (gold guidelines, 2016) for a period of at least 6 months prior to visit 1. * patients with moderate to severe stable copd: post-bronchodilator fev1 ≥ 30% and \<80% of the predicted normal and post-bronchodilator fev1/fvc \< 70% at visit 1. * patients with reversible airway obstruction defined as an increase in fev1 of at least 12% and 200 ml over the baseline value after four inhalations of albuterol sulfate 108 µg via a pmdi at visit 1. * current or former-smokers, with a smoking history of ≥ 10 pack-years. * patients able to perform acceptable and repeatable pulmonary function testing for fev1 according to the american thoracic society (ats)/european respiratory society (ers) 2005 criteria at visit 1. * patients eligible and able to participate in the study and who had signed an informed consent form prior to initiation of any study-related procedures. exclusion criteria: * patients with asthma. * any respiratory tract infection (including the upper respiratory tract) or copd exacerbation (including the mild copd exacerbation) within 6 weeks prior to visit 1 or during the run-in period. * patients hospitalized for a copd exacerbation (an emergency room visit for longer than 24 hours is considered a hospitalization) within 3 months prior to visit 1. * clinically significant respiratory conditions other than copd. * patients who in the investigator's opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to visit 1. * use of long-term oxygen therapy (≥ 15 hours/day). * patients who do not maintain regular day/night, waking/sleeping cycles including night shift workers. * clinically significant cardiovascular conditions. * patients with uncontrolled type i or type ii diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled hypertension. * patients with history of long qt syndrome or whose qtc (calculated according to fridericia's formula qtc=qt/rr1/3) \> 470 ms as indicated in the centralized reading report assessed at visit 1. * patients with clinically significant abnormalities in the laboratory tests, ecg parameters (other than qtc) or in the physical examination at visit 1 that might compromise patient safety. * patients with a history of hypersensitivity reaction to an inhaled medication or any component thereof, including paradoxical bronchospasm. * patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention or symptomatic unstable prostate hypertrophy. * history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer. * patients with any other serious or uncontrolled physical or mental dysfunction. * patients with a history (within 2 years prior to screening) of drug and/or alcohol abuse that may prevent study compliance based on the investigator judgment. * patients unlikely to be cooperative or who cannot comply with the study procedures. * patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to visit 1. * patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication. * patients unable to give consent, or patients of consenting age but under guardianship, or vulnerable patients. * any other conditions that, in the investigator's opinion, might render the patient to be unsuitable for the study. * involvement in the planning and/or conduct of the study (applies to astrazeneca staff and/or site staff), or patients employed by or relatives of the employees of the site or sponsor. * previous randomization in the present study d6571c00002.

Keywords: perforomist pressair copd cigarette smoking formoterol fumarate long-acting β2-adrenergic agonists (laba) long-acting muscarinic antagonists (lama)