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

NCT00642616 | Terminated Phase 3 Results DMC

• 1 other identifier: MKC-TI-134
• Study Type: interventional
• Target: 34
• Locations: 3 countries
• Sites: 21

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

Conditions

Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus; Moderate Chronic Obstructive Pulmonary Disease; Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants With Asthma Exacerbation by Treatment Arm

  Baseline to Week 52

• Number of Participants With COPD Exacerbation by Treatment Arm

  Baseline to Week 52

• Change in HbA1C From Baseline to Week 52

  Baseline, week 52

Study Arms (4)

Technosphere® Insulin (Asthma)

EXPERIMENTAL

Technosphere® Insulin Inhalation Powder administered prandially in diabetic participants with Asthma

Drug: Technosphere® Insulin

Usual Care (Asthma)

ACTIVE COMPARATOR

Usual anti diabetic care in Diabetic participants with Asthma

Drug: Usual Care

Technosphere® Insulin (COPD)

EXPERIMENTAL

Technosphere® Insulin Inhalation Powder administered prandially in diabetic participants with Chronic Obstructive Pulmonary disease (COPD)

Drug: Technosphere® Insulin

Usual Care (COPD)

ACTIVE COMPARATOR

Usual anti diabetic care in Diabetic participants with Chronic Obstructive Pulmonary disease (COPD)

Drug: Usual Care

Interventions

Technosphere® Insulin DRUG

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

Also known as: Afrezza

Technosphere® Insulin (Asthma); Technosphere® Insulin (COPD)

Usual Care DRUG

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

Usual Care (Asthma); Usual Care (COPD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (21)

Unknown Facility

Mission Hills, California, 91345, United States

Location

Unknown Facility

San Diego, California, 92117, United States

Location

Unknown Facility

Palm Harbor, Florida, 34684, United States

Location

Unknown Facility

Flint, Michigan, 48504, United States

Location

Unknown Facility

Morehead City, North Carolina, 28557, United States

Location

Unknown Facility

Medford, Oregon, 97504, United States

Location

Unknown Facility

Greenville, South Carolina, 29615, United States

Location

Unknown Facility

Spartanburg, South Carolina, 29302, United States

Location

Unknown Facility

Dallas, Texas, 75225, United States

Location

Unknown Facility

Dallas, Texas, 75231, United States

Location

Unknown Facility

Federal Way, Washington, 98003, United States

Location

Unknown Facility

Tacoma, Washington, 98405, United States

Location

Unknown Facility

Yaroslavl, RUS, 150002, Russia

Location

Unknown Facility

Kemerovo, RU, 650066, Russia

Location

Unknown Facility

Moscow, RU, 105120, Russia

Location

Unknown Facility

Saint Petersburg, RU, 191015, Russia

Location

Unknown Facility

Saint Petersburg, RU, 191119, Russia

Location

Unknown Facility

Saint Petersburg, RU, 194354, Russia

Location

Unknown Facility

Saint Petersburg, RU, 198013, Russia

Location

Unknown Facility

Kiev, UA, 04114, Ukraine

Location

Unknown Facility

Kyiv, UA, 01021, Ukraine

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Asthma

Interventions

Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

\- Early termination of trial leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

ContactUS@sanofi.com

Study Officials

• Chief Medical Officer

  Mannkind Corporation

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2008
• First Posted: March 25, 2008
• Study Start: March 1, 2009
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 14, 2017
• Results First Posted: February 15, 2016

Record last verified: 2017-04

Locations

US (12); RU (7); UA (2)