Evaluate Safety of Technosphere® Insulin (TI) in Diabetic Subjects With Moderate Obstructive Pulmonary Disease
Condition: Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus; Moderate Chronic Obstructive Pulmonary Disease; Asthma
MeSH terms: Asthma; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2
Intervention: Technosphere® Insulin; Usual Care
Intervention description: Technosphere® Insulin delivered with Gen 2 inhaler with doses individualized for each participant in combination with an antidiabetic regimen of insulin and/or oral antidiabetic agents; Type 1 diabetics: long-acting (basal) insulin plus rapid-acting insulin, or pre-mix insulin Type 2 diabetics: oral anti-diabetic medications with or without long-acting (basal) insulin
Intervention MeSH terms: Insulin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        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