Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Inhalation Insulin (TI) Inhalation Powder Using the Gen2 Inhaler

A Phase 3b, Multicenter, Open-label, Randomized, Forced-titration Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder, Using the Gen2 Inhaler, in Combination With Insulin Glargine Versus Insulin Aspart in Combination With Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Over a 16-week Treatment Period

This is an open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of Technosphere Insulin (TI) Inhalation Powder in combination with insulin glargine versus insulin aspart in combination with insulin glargine in subjects with type 2 diabetes.

Phase 3 clinical trial is designed to examine the efficacy and safety of inhaled prandial TI Inhalation Powder in combination with basal insulin verses insulin aspart in combination with basal insulin in subjects with type 2 diabetes who are suboptimally controlled with their current insulin regimens.This trial will employ a variety of methods to intensively manage these subjects.

Inclusion Criteria:

• Men and women ≥ 18 and ≤ 80 years of age

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

• Body mass index (BMI) ≤ 45 kg/m2

• Glycated Hemoglobin (HbA1c) > 6.5% and ≤ 10.0%

• Treatment with 1 to 3 Oral Antidiabetic Drugs (OADs) and basal insulin for a minimum of 3 months before screening. Doses of OADs must have been stable for 3 months before study entry

• Nonsmokers (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding ≥ 6 months

• Office spirometry at the investigator site

  • Forced expiratory volume in 1 second (FEV1) ≥ 65% Third National Health and Nutrition Examination Survey (NHANES III) predicted
  • Forced vital capacity (FVC) ≥ 65% NHANES III predicted
  • Forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1/FVC) ≥ lower limit of normal (LLN)

Exclusion criteria:

• Current or prior treatment with prandial or PreMix (70/30) insulin
• History of insulin pump use within 6 weeks of Visit 1
• Treatment with Glucagon-like Peptide (GLP-1) analog drugs within the preceding 12 weeks of Visit 1
• History of chronic obstructive pulmonary disease (COPD), 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 (eg, symptomatic autonomic neuropathy)
• Significant cardiovascular dysfunction or history within 3 months of Visit 1 (eg, congestive heart failure [New York Heart Association {NYHA} Class III or IV])
• Serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or any cerebrovascular accident
• History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening (Visit 1)