Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period

Inclusion Criteria

• Men and women = 18 years of age
• Clinical diagnosis of type 1 diabetes mellitus for at least 12 months
• Body mass index (BMI) = 38 kg/m2
• Stable dose of basal/bolus insulin therapy for at least 3 months with an FPG consistently < 220 mg/dL:
• HbA1c = 7.5% and = 10.0%
• Fasting C-peptide = 0.30 pmol/mL
• Subject willingness to not use CGM during the entire course of the trial
• Nonsmoking (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding 6 months
• Negative urine cotinine test, defined as = 100 ng/mL
• Lung function tests: • Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted
• Written informed consent

Exclusion Criteria

• Total daily insulin dose = 2 IU/kg/day. History of insulin pump use within 3 months of Screening or use of continuous glucose monitoring within 6 weeks of Screening
• History of inhaled insulin use in the previous 6 months
• Two or more unexplained severe hypoglycemic episodes within 3 months of Screening or an episode of severe hypoglycemia between Visit 1 and Visit 2. Unexplained refers to episodes of severe hypoglycemia that are not related to a dosing error, lack of or a change in meal size, or related to additional/unanticipated exercise
• Any hospitalization or emergency room visit due to poor diabetic control within 6 months of Screening, or hospitalization or emergency room visit due to poor diabetic control between Visit 1 and Visit 2
• Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the study, or a history of hypersensitivity to TI Inhalation Powder or to drugs with a similar chemical structure
• History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that affect HbA1c measurements.
• History of COPD, asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis), or use of any medications for these conditions
• Any clinically significant radiological findings on screening chest x-ray
• Active respiratory infection within 30 days before Screening (subject may return after 30 days from resolution for rescreening)
• Major organ system diseases, including: ? Seizure disorder; systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine; cancer (other than excised cutaneous basal cell carcinoma) or any history of lung neoplasms
• Current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity; use of medications for weight loss (eg, sibutramine, orlistat) within 12 weeks of Screening; treatment with amiodarone within 12 weeks of Screening
• Clinically significant abnormalities on screening laboratory evaluation or chest x-ray
• Severe complications of diabetes, in the opinion of the PI, including symptomatic autonomic neuropathy; disabling peripheral neuropathy; active proliferative retinopathy; nephropathy with renal failure, renal transplant, or dialysis; nontraumatic amputations due to gangrene; or vascular claudication
• Women who are pregnant, lactating, or planning to become pregnant during the clinical study period; women of childbearing potential (defined as premenopausal and not surgically sterilized or postmenopausal for fewer than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous, or transdermal contraceptives; condoms and diaphragms (double barrier) with a spermicide; or intrauterine devices. Postmenopausal for this study includes amenorrhea f
• Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the PI, would make the subject an unsuitable candidate for participation in the study
• Exposure to any investigational medications or devices within the previous 30 days before study entry
• Unable to read or write, or unlikely to comprehend and