TOPIC Trial for COPD

Inclusion Criteria:

- Male or Female age 40-65

- A clinical diagnosis of COPD as defined by GOLD

- At Least a 10 pack year smoking history

- Exhibit symptoms of chronic bronchitis defined by MRC

- FEV1% predicted ≥ 35% and ≤70% Post Bronchodilator

- Clinically stable in the last 4 weeks with no evidence of COPD exacerbation

- Weight of 40 kg-120 kg

- Willingness to use at least one form of acceptable birth control including
abstinence, condom with spermicide, or hormonal contraceptives

- Willing to monitor blood glucose if known history of diabetes mellitus requiring
insulin or medical therapy

Exclusion Criteria:

- Current Diagnosis of Asthma

- Daytime use of Oxygen Therapy

- Documented history of drug abuse within the last year

- Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary
disease within 28 days before receiving the first dose of study drug.

- Cirrhosis or elevated liver transaminases > 3X ULN

- GFR < 50 estimated by Cockcroft-Gault

- Any illness of abnormal lab finding that, in the opinion of the investigator or the
subject's general practitioner, might confound the results of the study or pose an
additional risk in administering study drug to the subject.

- Pregnant or Breastfeeding

- Subjects taking any inhibitors or inducers of CYP3A4, including certain herbal
medications and grapefruit/grapefruit juice.

- Uncontrolled Diabetes

- Excluded medications and foods include the drugs and foods provided in the appendix
document.

- Clinically significant arrhythmias or conduction abnormalities that in the opinion of
the investigator affect patient safety have been added as exclusion criteria and
criteria for withdrawal.

Patients who have not been stable or have been hospitalized in the past 3 months with any
clinically significant cardiac conditions.

Subjects with history of cancer (current or past, unless remote (>5years))except for
localized non-melanomatous skin cancers History of Stroke/CVA History of myocardial
infarction/acute coronary syndrome Cardiac Failure NYHC grade III-IV Diabetes Type I
Uncontrolled Hypertension Primary or secondary pulmonary hypertension