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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Moderate Chronic Obstructive Pulmonary Disease, Asthma

Intervention / Treatment
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* Drug: Technosphere® Insulin
* Drug: Usual Care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Technosphere® Insulin (Asthma)<br>Technosphere® Insulin Inhalation Powder administered prandially in diabetic participants with Asthma | Drug: Technosphere® Insulin<br>* 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<br>* Other names: Afrezza;|
| Active Comparator: Usual Care (Asthma)<br>Usual anti diabetic care in Diabetic participants with Asthma | Drug: Usual Care<br>* 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<br>|
| Experimental: Technosphere® Insulin (COPD)<br>Technosphere® Insulin Inhalation Powder administered prandially in diabetic participants with Chronic Obstructive Pulmonary disease (COPD) | Drug: Technosphere® Insulin<br>* 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<br>* Other names: Afrezza;|
| Active Comparator: Usual Care (COPD)<br>Usual anti diabetic care in Diabetic participants with Chronic Obstructive Pulmonary disease (COPD) | Drug: Usual Care<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Post-bronchodilator FEV1 From Baseline to Week 52 | Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) is measured at the pulmonary function laboratory. | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Asthma Exacerbation by Treatment Arm | Number of participants who experienced worsening of asthma symptoms | Baseline to Week 52 | 
| Number of Participants With COPD Exacerbation by Treatment Arm | Number of participants who experienced worsening of COPD symptoms | Baseline to Week 52 | 
| Change in HbA1C From Baseline to Week 52 |  | Baseline, week 52 |