AMPLIFY - D6571C00001 Duaklir USA Phase III Study

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.

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.