Evaluate Safety of Technosphere® Insulin (TI) in Diabetic Subjects With Moderate Obstructive Pulmonary Disease
Evaluate Safety of Technosphere® Insulin (TI) in Diabetic Subjects With Moderate Obstructive Pulmonary Disease
Examine the effects of TI in combination with an anti-diabetic regimen including inhaled
 insulin versus anti-diabetic treatment without inhaled insulin on lung function & pulmonary
 safety
Inclusion Criteria:

 Asthma

 -  Physician diagnosis of asthma with history of any or all of the following: recurrent
 wheezing, recurrent chest tightness, recurrent difficulty breathing, or cough,
 particularly worse at nighttime

 -  Never smoked or former smokers (= 6 months since cessation)

 -  ≥18 years of age

 -  Prebronchodilator Forced Expiratory Volume in 1sec (FEV1) ≥ 60% Third National Health
 and Nutrition Examination Survey (NHANES III) predicted, prebronchodilator total lung
 capacity (TLC) ≥ 80% predicted Intermountain Thoracic Society (ITS), and
 prebronchodilator single breath carbon monoxide diffusing capacity of the lung (DLco)
 (unc) ≥70% predicted (Miller)

 -  < 30% day-to-day variability in daily morning Peak expiratory Volume (PEF) during the
 2-week run-in period

 -  Significant improvement in pre- to postbronchodilator spirometry (defined as an
 increase from baseline of ≥ 12% and ≥ 200 mL in FEV1 or Forced Vital Capacity [FVC])
 at Screening/Visit 1 or documented significant improvement in pre- to
 postbronchodilator spirometry (as defined above) within past 12 months in subject's
 medical records or a documented positive methacholine challenge test within the past
 12 months

 COPD

 -  Physician diagnosis of COPD (including emphysema and/or chronic bronchitis), history
 of dyspnea and/or intermittent or daily chronic cough with or without sputum
 production, not attributable to any other known cause

 -  Former smoker (≥ 6 months since cessation) with smoking history of ≥ 10 pack years

 -  ≥40 years of age

 -  Postbronchodilator FEV1/FVC ratio < 70%

 -  Postbronchodilator FEV1 ≥ 50% NHANES III predicted, total lung capacity (TLC) ≥ 80%
 predicted ITS, and DLco (unc) ≥ 50% predicted (Miller)

 Both

 -  Clinical diagnosis of Type1 or 2 diabetes mellitus for ≥ 12 months and no change in
 anti-diabetic regiment for at least 90-days prior to screening

 -  BMI of, < 39 kg/m2

 -  Urine cotinine level ≤ 100ng/dL

 -  Clinical diagnosis of obstructive lung disease

 -  HbA1C > 6.5% ≤ 11.5%

 Exclusion Criteria:

 -  History of pulmonary exacerbation within 8 weeks of screening/V1 or between V1 and V2

 -  Use of systemic corticosteroids or antibiotics for respiratory illness within 8 weeks
 of screening/V1 OR between V1 and V2

 -  Increase from baseline in the use of short-acting bronchodilator or short-acting
 anticholinergic agents, or the combination of the 2, by ≥6 puffs or ≥3 nebulizer
 treatments per day for ≥ 2 days

 -  Treatment with supplemental oxygen therapy, room air oxygen saturation, 94% or history
 of intubation or ICU admission for respiratory illness in the past 5 yrs.

 -  Greater than 2 hospitalizations or ER or urgent care visits or required >3 courses of
 systemic steroid in the past 12 months for respiratory illness

 -  Use of Symlin® (pramlintide acetate) within the preceding 90 days

 -  Two or more severe hypoglycemic episodes within 6 months of screening or episode of
 severe hypoglycemia between Screening and Baseline

 -  Previous exposure to any inhaled insulin product

 -  Currently using an insulin delivery pump

 -  Requires significant change (define as initiation of a new medication or change in the
 dose or frequency of the controller medications) in the asthma or COPD therapeutic
 regimen within 8 weeks of Screening/Visit 1 (Week -4) or between Visit 1 and
 Baseline/Visit 2

 -  Severe complications of diabetes mellitus, in the opinion of the PI or
 sub-investigator, including symptomatic autonomic neuropathy; disabling peripheral
 neuropathy; active proliferative retinopathy; nephropathy with renal failure, renal
 transplant and/or dialysis; history of foot ulcers; nontraumatic amputations due to
 gangrene; and/or vascular claudication