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

This study has been terminated.
(Terminated upon recommendation of the Data Safety Monitoring Board (DSMB))
Sponsor:
Collaborator:
Mannkind Corporation
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00642616
First received: March 21, 2008
Last updated: February 12, 2016
Last verified: February 2016
  Purpose
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

Condition Intervention Phase
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Moderate Chronic Obstructive Pulmonary Disease
Asthma
Drug: Technosphere® Insulin
Drug: Usual Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change in Post-bronchodilator FEV1 From Baseline to Week 52 [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
    Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) is measured at the pulmonary function laboratory.


Secondary Outcome Measures:
  • Number of Participants With Asthma Exacerbation by Treatment Arm [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]
    Number of participants who experienced worsening of asthma symptoms

  • Number of Participants With COPD Exacerbation by Treatment Arm [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]
    Number of participants who experienced worsening of COPD symptoms

  • Change in HbA1C From Baseline to Week 52 [ Time Frame: Baseline, week 52 ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: March 2009
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00642616

Locations
United States, California
Mission Hills, California, United States, 91345
San Diego, California, United States, 92117
United States, Florida
Palm Harbor, Florida, United States, 34684
United States, Michigan
Flint, Michigan, United States, 48504
United States, North Carolina
Morehead City, North Carolina, United States, 28557
United States, Oregon
Medford, Oregon, United States, 97504
United States, South Carolina
Greenville, South Carolina, United States, 29615
Spartanburg, South Carolina, United States, 29302
United States, Texas
Dallas, Texas, United States, 75225
Dallas, Texas, United States, 75231
United States, Washington
Federal Way, Washington, United States, 98003
Tacoma, Washington, United States, 98405
Russian Federation
Yaroslavl, RUS, Russian Federation, 150002
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
Ukraine
Kiev, UA, Ukraine, 04114
Kyiv, UA, Ukraine, 01021
Sponsors and Collaborators
Sanofi
Mannkind Corporation
Investigators
Study Chair: Chief Medical Officer Mannkind Corporation
  More Information

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00642616     History of Changes
Other Study ID Numbers: MKC-TI-134 
Study First Received: March 21, 2008
Results First Received: November 23, 2015
Last Updated: February 12, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Respiratory Tract Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 24, 2016