AMPLIFY - D6571C00001 Duaklir USA Phase III Study

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).

This study was conducted to assess the bronchodilator efficacy and safety as well as effect on health related quality of life of AB/FF 400/12 μg compared to the individual components (AB 400 μg and FF 12 μg) in COPD patients. The trial duration of 24 weeks allows the assessment of the effect on symptoms improvement of the combined treatments versus individual components as well as the long term bronchodilation comparison between AB 400 μg and TIO 18 μg in minimizing the risk of COPD exacerbations in current or former smokers, aged ≥40 in symptomatic COPD patients.

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.