A Study Comparing Subcutaneous Rapid Acting Insulin and One Formulation of Inhaled Insulin in Subjects With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Technosphere Insulin
Intervention description: Inhalation 15U/30U
Intervention MeSH terms: Insulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Inhaled Insulin

Summary:

      The original protocol was a randomized, open-label, 3-way cross-over study with 9 scheduled
      visits. The visits comprised an initial screening visit, 3 treatment visits for the meal
      challenge followed by a 2-6-week blood-loss recovery period, an interim safety visit, 3
      sequential visits for the glucose clamp, and a final close-out visit.

      Protocol Amendment 1 was a randomized, open-label, 2-way cross-over study with 7 visits for
      each completed subject. The visits comprise an initial screening visit, 2 treatment visits
      for the meal challenge followed by a 2-6-week blood-loss recovery period, an interim safety
      visit, 2 sequential visits for the glucose clamp, and a final close-out visit.

      For both the original protocol and Protocol Amendment 1, subjects were hospitalized in the
      clinical unit for all procedures.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Receiving diabetes treatment with insulin for a minimum of 3 months

          -  Body Mass Index (BMI) of ≤ 34 kg/m2 and ≥ 25 kg/m2

          -  HbA1c ≤ 8.5% based upon results from a central laboratory

          -  Non-smoking Males and females ≥ 18 and ≤ 70 years of age

          -  A clinical diagnosis of type 2 diabetes mellitus for ≥ 12 months

        Exclusion Criteria:

          -  Total daily insulin requirement of ≥ 1.2 U/kg body weight

          -  Use of Symlin® (pramlintide acetate) and/or Byetta® (exenatide) within the preceding 8
             weeks

          -  Two or more severe hypoglycemic episodes within 6 months of screening

          -  Any hospitalization or emergency room visit due to poor diabetic control within 6
             months of Screening

          -  Severe complications of diabetes

          -  Previous exposure to any inhaled insulin product

          -  Currently using an insulin delivery pump

          -  Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the
             trial

          -  Any clinically important pulmonary disease, confirmed by documented history, pulmonary
             function testing, or radiologic findings

          -  Chronic use of systemic steroids

          -  Inability to perform PFT maneuvers to meet the recommended American Thoracic Society
             (ATS) standards of acceptability and repeatability

          -  Significant improvement in spirometry following bronchodilation

          -  Active respiratory infection

          -  Seizure disorder

          -  Significant cardiovascular dysfunction and/or history within 3 months of Screening

          -  Uncontrolled hypertension with a systolic blood pressure of >160 mm Hg and/or
             diastolic blood pressure > 95 mm Hg at screening, despite pharmacologic treatment

          -  Clinical nephrotic syndrome or renal dysfunction or disease

          -  Cancer (other than an excised cutaneous basal cell carcinoma) within the past 5 years
             or any history of lung neoplasms

          -  History of active viral and/or cirrhotic hepatic disease and/or abnormal liver enzymes

          -  Active infection eg, Human Immunodeficiency Virus (HIV), Hepatitis, or history of
             severe infection within 30 days of Screening

          -  Anemia

          -  A previous diagnosis of systemic autoimmune or collagen vascular disease requiring
             prior or current treatment with systemic corticosteroids, cytotoxic drugs or
             penicillamine

          -  Any concurrent illness, other than diabetes mellitus not controlled by a stable
             therapeutic regime

          -  Current or previous chemotherapy or radiation therapy that may result in pulmonary
             toxicity

          -  Clinically significant abnormalities on screening laboratory evaluation

          -  Female subjects who are pregnant, lactating or planning to become pregnant during the
             clinical trial period

          -  Female subjects of childbearing potential (defined as pre-menopausal and not
             surgically sterilized or post-menopausal for less than 2 years) not practicing
             adequate birth control.

          -  Current drug or alcohol abuse, or a history of drug or alcohol abuse, that, in the
             opinion of the PI, would not make the subject a suitable candidate for participation
             in the clinical trial

          -  Exposure to any investigational medications or devices within the previous 30 days
             prior to trial entry or participation in another clinical trial during this trial

          -  Unable and/or unlikely to comprehend and/or follow the trial protocol

          -  Concurrent medical or major psychiatric condition which, in the opinion of the PI,
             makes the subject unsuitable for the clinical trial, or could limit the validity of
             the informed consent and/or impair the subject's ability to participate in the trial