Adherence Study in COPD Patients

Chronic obstructive pulmonary disease (COPD) is a common disease with substantial associated
morbidity and mortality. COPD is the third leading cause of death in the US and claimed
133,965 US lives in 2009. In 2011 12.7 million US adults were estimated to have COPD.
However, approximately 24 million US adults have evidence of impaired lung function,
indicating an under diagnosis of COPD. COPD also has a potentially harmful economic impact.
In 2010, COPD resulted in over 10 million office visits, nearly 1.5 million emergency
department visits, 700,000 hospitalizations, and 133,575 deaths in the US. In 2010, US total
medical treatment costs attributed solely to COPD (i.e., excluding comorbidities) were
estimated to be $32.1 billion with an additional $3.9 billion in COPD costs resulting from
worker absenteeism. Even in industrialized countries such as the US, where anti-smoking
initiatives have been relatively successful, the legacy of past smoking behavior in aging
populations ensures that the COPD burden will unavoidably continue to climb over the next 20
to 30 years. Adherence rates for inhaled combination therapy is poor (average 3.9 refills per
year). COPD patients with lower adherence tend to have higher overall healthcare costs, as
demonstrated in a 24 month study of 33,816 patients in the US, which found: Patients
continuing therapy had lower costs of care by $3764 compared with patients who had ceased to
take their maintenance therapy. COPD patients with higher adherence to prescribed regimens
experienced fewer hospitalizations and lower Medicare costs (-$2185) than those who exhibited
lower adherence behaviors. Given the poor adherence with inhaled combination therapy seen in
patients with COPD, and associated morbidity/mortality and economic costs, the present study
is being conducted to see if medication reminders can be used to improve adherence in this
population.

Inclusion Criteria:

For inclusion in the study subjects should fulfil the following criteria:

- Signed informed consent at Visit 1 prior to any study specific procedures

- Outpatient adults 40 years and older

- A diagnosis of COPD confirmed by a post-bronchodilator Forced Expiratory Volume in 1
second/Forced Vital Capacity (FEV1/FVC) <0.70 at some point in the past 3 years.

- Moderate to Very Severe COPD as defined by a post-bronchodilator FEV1 <80% of
predicted on most recent spirometry.

- Had been on an ICS/LABA combination therapy of a brand and dose approved forCOPD, for
at least 3 months prior to screening.

- Current or previous smoker with a smoking history equivalent to 10 or more pack years
(1 pack year = 20 cigarettes smoked per day for 1 year).

- Willing to discontinue all medications containing both a LABA and an ICS and to begin
Symbicort 160/4.5 μg, 2 inhalations bid.

- Must be willing to make a return visit, and complete all study assessments for the
duration of study.

- Life expectancy >12 months.

- Must be willing to comply with all study procedures including being able to remove and
attach device to the inhaler.

- Must be able and willing to read and write/respond using the electronic device
provided.

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are
fulfilled:

- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).

- Previous randomization in the present study.

- Patients who have been randomized in a clinical study and received an investigational
product within 30 days of Visit 1 (participation is defined as the completion of a
treatment related visit).

- Current diagnosis of asthma.

- Known history of drug or alcohol abuse which, in the opinion of the Investigator, may
interfere with subject's ability to participate or comply with the study.

- An acute exacerbation of COPD that required hospitalization or emergency room visit or
treatment with systemic steroids and/or antibiotics during the 28 days before Visit 1.
Patients who had a COPD exacerbation within 28 days of Visit 1 can be re-screened
once. Re-screening can occur no earlier than 28 days from the last dose of systemic
steroids and/or antibiotics and/or hospitalization, whichever is later.

- Enrolled patients that have a COPD exacerbation during the run-in period, defined as
worsening symptoms which in the judgment of the Investigator requires treatment with
systemic steroids and/or antibiotics and/or hospitalization. Patients who had a COPD
exacerbation during the run-in period can be re-screened once. Re-screening can occur
no earlier than 28 days from the last dose of systemic steroid and/or antibiotics
and/or hospitalization, whichever is later.

- Any hospital admissions due to ischemic heart disease or heart failure within 3 months
of study enrollment.

- Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurologic,
musculoskeletal, endocrine, metabolic, infectious, psychiatric, major physical
impairment) which, in the opinion of the Investigator, may either put the patient at
risk because of participation in the study, or may influence the results of the study,
or the patient's ability to participate in the study.

- History of lung or upper airway cancer and any other malignancy not in remission for 5
years or more, except for patients who have had basal cell carcinoma, or in situ
carcinoma of the cervix provided that the patient is in remission and curative therapy
was completed at least 12 months prior to the date informed consent was obtained.

- Use or planned use of systemic corticosteroids as a maintenance treatment (defined as
daily or every other day treatment for 21 or more days) for inflammatory or
immunologic conditions unrelated to their COPD.

- Planned hospitalization or surgical procedure requiring inpatient stay during the
study.

- Pregnancy, breast-feeding or planned pregnancy during the study; fertile women not
using acceptable contraceptive measures, as judged by the Investigator. Female
subjects who are not post-menopausal or surgically sterile must have a negative urine
pregnancy test (urine dipstick test only) prior to randomization and must comply with
contraceptive methods.

- Any clinically relevant abnormal findings in physical examination or vital signs,
which in the opinion of the Investigator, may put the patient at risk because of
his/her participation in the study.

- Known or suspected hypersensitivity to the study therapy (Symbicort).

- Patients who are unable or unwilling to use mobile communication devices, or patients
who plan to be away from home for a significant part of the study without access to
cellular connectivity are excluded because of the challenges of collecting data and
providing information to these patients who are unable to use the service.

- Patients with thoracic surgery within 6 months of Visit 1.

- Patients who have received a lung transplant or are currently active on the lung
transplant waiting list.