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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT00309244
First received: March 27, 2006
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Type 2
Drug: Technosphere® Insulin Inhalation Powder
Drug: 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Prospective, Multi-Center, Open-Label, Randomized, Controlled Clinical Trial Comparing the 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

Resource links provided by NLM:


Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • Change From Baseline in HbA1c to Week 52 [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in Weight to Week 52 [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Plasma Glucose to Week 52 [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Number of Subjects Achieving Week 52 HbA1c Levels Less Than or Equal to 7.0% [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  • Incidence of Total Hypoglycemia [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
    Defined as hypoglycemic symptoms that are relieved with carbohydrate intake or blood glucose measurement <= 63 mg/dL, regardless of symptoms.

  • Incidence of Severe Hypoglycemia [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]

    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.

  • Total Hypoglycemia Event Rate [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
    Number of Hypoglycemic Events/Total Subject Exposure Time (in months)

  • Severe Hypoglycemia Event Rate [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]
    Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)


Enrollment: 677
Study Start Date: February 2006
Study Completion Date: September 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TI + Insulin glargine
Technosphere® Insulin Inhalation Powder + insulin glargine
Drug: Technosphere® Insulin Inhalation Powder
Inhalation, 15U/30U
Active Comparator: BPR 70/30
70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin)
Drug: 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin)
BPR 70/30, which is a premix of intermediate acting and rapid acting insulin given sc

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00309244

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Sponsors and Collaborators
Mannkind Corporation
  More Information

No publications provided by Mannkind Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT00309244     History of Changes
Other Study ID Numbers: MKC-TI-102
Study First Received: March 27, 2006
Results First Received: July 22, 2014
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin Aspart
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014