Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)
Condition: Chronic Obstructive Pulmonary Disease - COPD
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Formoterol fumarate (6 μg); Formoterol furmarate (20 μg); Placebo for formoterol fumarate; Formoterol fumarate (12 μg); Formoterol fumarate (40 μg)
Intervention description: Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI); Oral Inhalation (via a standard jet nebulizer connected to an air compressor.; Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI); Oral Inhalation (by Pressair® Dry Powder Inhaler, DPI); Oral Inhalation (via a standard jet nebulizer connected to an air compressor.
Intervention MeSH terms: Pharmaceutical Solutions; Formoterol Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 132.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Perforomist; Pressair; COPD; Cigarette smoking; Formoterol fumarate; long-acting β2-adrenergic agonists (LABA); long-acting muscarinic antagonists (LAMA)

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).
    

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.