AMPLIFY - D6571C00001 Duaklir USA Phase III Study
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Aclidinium bromide 400 μg/Formoterol Fumarate 12 μg (AB/FF 400/12 μg); Aclidinium bromide 400 μg (AB 400 μg); Formoterol fumarate 12 μg (FF 12 μg); Placebo to AB/FF 400/12 μg, AB 400 μg and FF 12 μg; Tiotropium 18 μg (TIO 18 μg); Placebo to TIO 18 μg
Intervention description: Inhalation powder; Inhalation powder; Inhalation powder; Inhalation powder; Powder in capsules for oral inhalation; Powder in capsules for oral inhalation
Intervention MeSH terms: Bromides; Formoterol Fumarate; Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1595.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Safety; Efficacy; Aclidinium bromide; Formoterol fumarate; Tiotropium; Bronchodilation; COPD

Summary:

      This is a multiple dose, randomized, parallel, double-blind, double-dummy, multicenter and
      multinational Phase III study to determine the efficacy and safety of Aclidinium bromide
      400μg/Formoterol Fumarate (AB/FF) 12 μg compared to individual components and TIO
      (Tiotropium) 18 μg when administered to patients with stable chronic obstructive pulmonary
      disease (COPD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult male or non-pregnant, non-lactating female patients aged ≥40.

          -  Patients with diagnosis of moderate to very severe stable COPD: post-bronchodilator
             FEV1 < 80% of the predicted normal and post-bronchodilator FEV1/FVC < 70% at Screening
             Visit.

          -  Symptomatic patients with a CAT score ≥10 at Screening and Randomization visit (Visits
             1 and 2).

          -  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:

          -  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 D6571C00001.

          -  Patients with predominant asthma.

          -  Any respiratory tract infection (including the upper respiratory tract) or COPD
             exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening
             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 Screening Visit.

          -  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 Screening.

          -  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 centralised reading
             report assessed at Screening.

          -  Patients with clinically significant abnormalities in the laboratory tests, ECG
             parameters (other than QTc) or in the physical examination at Screening Visit that
             might comprise patient safety.

          -  Patient with known non-controlled history of infection with human immunodeficiency
             virus and/or active hepatitis.

          -  Patient with a history of hypersensitivity reaction to inhaled medication or any
             component thereof, including paradoxical bronchospasm.

          -  Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute
             urinary retention or symptomatic non-stable 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 that cannot comply with the study procedures.

          -  Patients treated with any investigational drug within 30 days (or 6 half-lives,
             whichever is longer) prior to Screening.

          -  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. Patients who demonstrate < 80% compliance with the electronic
             diary during the run-in period.