Evaluate Safety of Technosphere® Insulin (TI) in Diabetic Subjects With Moderate Obstructive Pulmonary Disease

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