Efficacy and Safety in Subjects With Type 2 Diabetes Receiving Subcutaneous Basal Insulin and Prandial Inhalation of Technosphere/Insulin Versus Subcutaneous Premixed Insulin Therapy Over a 52-Week Treatment Period and a 4-Week Follow-up
- Conditions
- Diabetes Type 2
- Interventions
- Drug: 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin)Drug: Technosphere® Insulin Inhalation Powder
- Registration Number
- NCT00309244
- Lead Sponsor
- Mannkind Corporation
- Brief Summary
The purpose of this 13 month study (12 month treatment period and 1 month follow-up period) is to determine whether inhaled insulin is safe and effective in the treatment of type 2 diabetes.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 677
- Men or women ≥ 18 and ≤ 80 years old
- Clinical diagnosis of type 2 diabetes mellitus
- HbA1c > 7.0% and ≤ 11.0%
- BMI ≤ 40 kg/m2
- Negative smoking status and urine cotinine test
- Written informed consent
- Receiving sc insulin 2-3 times daily administered as any of the following 3 regimens: self-mix regimen, pre-mix regimen, or long-acting analogue and regular or rapid-acting insulin analogue not to exceed 3 daily injections. Subjects may also have received oral antidiabetic agents including metformin or thiazolidinediones.
- No dose adjustments for insulin and oral antidiabetic agents within the preceding 6 weeks.
- FEV1 ≥ 70% of NHANES III predicted; TLC) ≥ 80% of predicted (Intermountain Thoracic Society); DLCO uncorrected ≥ 70% of predicted
- Total daily dose of insulin ≥1.4 IU/kg body weight
- Treatment with any sulfonylureas and/or meglitinides and/or alpha-glucosidase inhibitors within the preceding 8 weeks
- Treatment with pramlintide acetate (Symlin®), and/or any incretins (e.g., exenatide [Byetta®]) within the preceding 8 weeks
- Unstable diabetes mellitus control, defined as 2 or more episodes of severe hypoglycemia (requiring third party intervention) and/or any hospitalization or emergency room visit due to poor diabetic control or hyperglycemia requiring hospitalization within the preceding 6 months
- Exposure to an inhaled insulin at any time, treatment with an investigational drug within the preceding 3 months, and/or current participation in another clinical trial
- Allergy to insulin or to any drugs to be used as part of the clinical trial, or history of hypersensitivity to the investigational drug or to drugs of similar chemical structures
- History of active viral and/or cirrhotic hepatic disease and/or abnormal liver enzymes as evidenced by serum aspartate aminotransferase (AST)and/or alanine aminotransferase (ALT) ≥ 3 x Upper Limit of Normal (ULN)(Includes active hepatitis A, positive hepatitis B and/or hepatitis C serology)
- Serum creatinine > 1.8 mg/dL in women and > 2.0 mg/dL in men History of chronic obstructive pulmonary disease (COPD), asthma (any history of bronchospasm or asthma after the age of 14), and/or any other clinically important pulmonary disease confirmed by documented history, pulmonary function testing, or radiologic findings
- Congestive heart disease graded as class III or class IV according to New York Heart Association criteria and subjects currently being treated pharmacologically for ventricular dysrhythmias using amiodarone
- History of myocardial infarction, cardiac surgery, coronary angioplasty, and/or stroke within the preceding 3 months
- Symptomatic coronary artery disease, including crescendo angina, unstable angina, and/or unstable or symptomatic cardiac arrhythmias
- Poorly controlled arterial hypertension despite pharmacologic treatment, defined as systolic blood pressure (BP) > 180 mm Hg and/or diastolic BP > 110 mm Hg at screening
- History of malignancy within the preceding 5 years (other than excised basal cell carcinoma of the skin), any history of lung neoplasm, and/or subjects with current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity
- History of acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or positive human immunodeficiency virus (HIV) serology
- Prior diagnosis of systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine
- Visit 1/Screening (Week -3), but prior to Visit 1 PFTs and before Visit 3/Baseline (Week 0), subject will be scheduled for PFTs after 30 days from resolution of respiratory infection. An additional hemoglobin and urine β-HCG (for women of childbearing potential age only) will be required
- Women who are pregnant, lactating or planning to become pregnant
- Women of childbearing potential (defined as pre-menopausal and not surgically sterilized or postmenopausal for less than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous and/or transdermal contraceptives; condoms and diaphragms with a spermicide, or intrauterine devices
- Current drug and/or alcohol abuse
- Subjects who in the opinion of the Investigator will be unable to comply with the requirements of the protocol
- Severe complications of diabetes mellitus, in the opinion of the 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
- Any other concurrent medical or major psychiatric condition which, in the opinion of the Investigator, makes the subject unsuitable for the clinical trial, or could limit the validity of the ICF and/or impair the subject's ability to participate in the trial
- Inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) acceptability and repeatability criteria.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BPR 70/30 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin) 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin) TI + Insulin glargine Technosphere® Insulin Inhalation Powder Technosphere® Insulin Inhalation Powder + insulin glargine
- Primary Outcome Measures
Name Time Method Change From Baseline in HbA1c to Week 52 Baseline to Week 52
- Secondary Outcome Measures
Name Time Method Change From Baseline in Weight to Week 52 Baseline to Week 52 Incidence of Severe Hypoglycemia 52 Weeks Severe hypoglycemia occurs when all 3 of the following occur simultaneously:
* Subject requires the assistance of another person;
* Subject exhibits at least 1 cognitive neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, seizure, loss of consciousness);
* Measured BG is ≤ 49 mg/dL (2.7 mmol/L), or, in the absence of a BG measurement, clinical symptoms are reversed by oral carbohydrates, sc glucagon or intravenous glucose administration; OR,
* Measured BG is ≤ 36 mg/dL (2.0 mmol/L) with or without symptoms.Change From Baseline in Fasting Plasma Glucose to Week 52 Baseline to Week 52 Incidence of Total Hypoglycemia 52 Weeks Defined as hypoglycemic symptoms that are relieved with carbohydrate intake or blood glucose measurement \<= 63 mg/dL, regardless of symptoms.
Total Hypoglycemia Event Rate 52 Weeks Number of Hypoglycemic Events/Total Subject Exposure Time (in months)
Severe Hypoglycemia Event Rate 52 Weeks Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)
Number of Subjects Achieving Week 52 HbA1c Levels Less Than or Equal to 7.0% Week 52
Trial Locations
- Locations (149)
Coastal Clinical Research Inc
🇺🇸Mobile, Alabama, United States
Quality of Life Medical & Research Center
🇺🇸Tucson, Arizona, United States
Southern Arizona VA Healthcare System
🇺🇸Tucson, Arizona, United States
Tucson Clinical Research
🇺🇸Tucson, Arizona, United States
International Clinical Research Network
🇺🇸Chula Vista, California, United States
Saad Hijazi MD Inc
🇺🇸Fresno, California, United States
Valley Research
🇺🇸Fresno, California, United States
Diabetes/Lipid Management and Research Center
🇺🇸Huntington Beach, California, United States
South Bay Clinical Research
🇺🇸Inglewood, California, United States
Southern California Endocrine Center
🇺🇸Pasadena, California, United States
Scroll for more (139 remaining)Coastal Clinical Research Inc🇺🇸Mobile, Alabama, United States