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

A Phase 3, Open-label, Randomized Clinical Trial to Evaluate the Safety of Technosphere® Insulin Inhalation Powder in Type 1 or Type 2 Diabetic Subjects With Obstructive Pulmonary Disease (Asthma or Chronic Obstructive Pulmonary Disease) Over a 12 Months Treatment Period With a 2 Month Follow-up

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