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

Phase 3

Terminated

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

Interventions: Drug: Technosphere® Insulin
Drug: Usual Care

Registration Number: NCT00642616

Lead Sponsor: Mannkind Corporation

Brief 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 34

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Technosphere® Insulin (Asthma)	Technosphere® Insulin	Technosphere® Insulin Inhalation Powder administered prandially in diabetic participants with Asthma
Usual Care (Asthma)	Usual Care	Usual anti diabetic care in Diabetic participants with Asthma
Technosphere® Insulin (COPD)	Technosphere® Insulin	Technosphere® Insulin Inhalation Powder administered prandially in diabetic participants with Chronic Obstructive Pulmonary disease (COPD)
Usual Care (COPD)	Usual Care	Usual anti diabetic care in Diabetic participants with Chronic Obstructive Pulmonary disease (COPD)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With COPD Exacerbation by Treatment Arm	Baseline to Week 52	Number of participants who experienced worsening of COPD symptoms
Number of Participants With Asthma Exacerbation by Treatment Arm	Baseline to Week 52	Number of participants who experienced worsening of asthma symptoms
Change in HbA1C From Baseline to Week 52	Baseline, week 52