Comparison of Technosphere® Insulin Versus Technosphere Powder (Placebo) in Insulin-Naive Subjects With Type 2 Diabetes Mellitus

A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized, Clinical Trial Evaluating the Efficacy and Safety of Prandial Technosphere® Insulin Inhalation Powder Versus Technosphere Inhalation Powder in Insulin Naïve Subjects With Type 2 Diabetes Mellitus Poorly Controlled With Oral Antidiabetic Agents Over a 24 Week Treatment Period

Insulin-naive subjects with Type 2 Diabetes Mellitus who are sub-optimally controlled on either maximum tolerated dose of metformin or maximum tolerated dose of metformin plus one or two other oral anti-diabetic medications will have either Prandial Technosphere® Insulin or Technosphere Powder (placebo) added to their oral antidiabetic drugs.

Inclusion Criteria:

• HbA1c > or = to 7.5% and < or = to 10.0%

• Body mass index (BMI) < or = to 45 kg/m2

• Non smoker for at least 6 months before Screening

• Clinical diagnosis of type 2 diabetes mellitus for more than 12 months

• Currently receiving as diabetes treatment only metformin or 2 or more OADs and on stable doses for at least 3 months before enrollment

  • Subjects receiving metformin must be on at least 1.5gm daily, or up to the maximum tolerated dose
  • Subjects treated with a sulfonylurea must be on at least 50% of the total maximum approved dose for a given agent
  • Subjects receiving a DPP-4 inhibitor must receive the maximum approved dose specific for that agent
  • Metiglinide and alpha-glucoside inhibitors must be taken at the highest tolerated dose within the approved dose range

• No previous or current treatment with insulin, except during an acute illness, gestational diabetes, or at time of initial diagnosis of diabetes

• Forced expiratory volume in one second (FEV1) > or = to 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted

• Forced vital capacity (FVC) > or = to 70% NHANES III predicted

• Forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC) > or = to NHANES III lower limit of normal (LLN)

Exclusion Criteria:

• History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis)
• Any clinically significant radiological findings on screening chest x-ray
• Use of medications for asthma, COPD, or any other chronic respiratory conditions
• Evidence of serious complications of diabetes (proliferative retinopathy, autonomic neuropathy with symptoms of gastroparesis or cardiac arrhythmia; sensory neuropathy that makes manipulation of the Gen2C inhaler difficult)
• Renal disease or renal dysfunction
• Significant cardiovascular dysfunction or history thereof within 12 months of screening; serious arrhythmia, treatment with medications to control/treat arrhythmias; myocardial infarction; cardiac surgery; history of valvular heart disease
• Previous or current use of amiodarone
• Treatment with glucagon-like peptide-1 (GLP-1) analogs, thiazolidinediones (TZD), or weight loss drugs (eg, sibutramine, orlistat) within 3 months of screening
• History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening
• History of recent blood transfusion (within previous 3 months) or diagnosis of hemoglobinopathies that may affect HbA1c measurements