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

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus; Asthma; Type 1 Diabetes Mellitus; Moderate Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Technosphere® Insulin; Drug: Usual Care

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • RU
    • Kemerovo, RU, Russian Federation, 650066
    • Moscow, RU, Russian Federation, 105120
    • St Petersburg, RU, Russian Federation, 198013
    • St. Petersburg, RU, Russian Federation, 191015
    • St. Petersburg, RU, Russian Federation, 191119
    • St. Petersburg, RU, Russian Federation, 194354
  • RUS
    • Yaroslavl, RUS, Russian Federation, 150002
• Ukraine
  • UA
    • Kiev, UA, Ukraine, 04114
    • Kyiv, UA, Ukraine, 01021
• United States
  • California
    • Mission Hills, California, United States, 91345
    • San Diego, California, United States, 92117
  • Florida
    • Palm Harbor, Florida, United States, 34684
  • Michigan
    • Flint, Michigan, United States, 48504
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
  • Oregon
    • Medford, Oregon, United States, 97504
  • South Carolina
    • Greenville, South Carolina, United States, 29615
    • Spartanburg, South Carolina, United States, 29302
  • Texas
    • Dallas, Texas, United States, 75231
    • Dallas, Texas, United States, 75225
  • Washington
    • Federal Way, Washington, United States, 98003
    • Tacoma, Washington, United States, 98405

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mannkind Corporation
• Investigators: Study Chair: Chief Medical Officer, Mannkind Corporation

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 21, 2008
• First Submitted That Met QC Criteria: March 24, 2008
• First Posted (Estimate): March 25, 2008

Study Record Updates

• Last Update Posted (Actual): April 14, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Hypersensitivity, Immediate; Endocrine System Diseases; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Asthma; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: MKC-TI-134