Clamp Study Comparing Inhalation of Technosphere®/Insulin in Smokers and Non-Smokers With Type 2 Diabetes

Exclusion Criteria

• •Diabetes mellitus type 1.
• •Total daily insulin requirement of = 1.4 U/kg.
• •Intake of any drug or herbal preparation which, in the evaluation of the Investigator, may interfere with the clinical trial results by causing clinically relevant interference with glucose utilization, insulin action, or recovery from hypoglycemia (eg, systemic corticosteroids, oral or inhaled glucocorticosteroids).
• •History of hypersensitivity to the trial drug or to drugs with similar chemical structures.
• •Treatment with any investigational drug within 90 days prior to enrollment of trial.
• •Progressive fatal disease.
• •History of malignancy within five years of trial entry (other than basal cell carcinoma).
• •Evidence of severe secondary complications of diabetes (neuropathy, nephropathy as evidenced by creatinine \> 1.6 mg/dL for females or \> 1.8 mg/dL for males, Stage III or IV retinopathy (according to the MKC diabetic retinopathy scale, see Appendix 1.1 of protocol), or severe peripheral vascular disease).
• •Previous history of anaphylaxis or angioedema.
• •Evidence of clinically significant autonomic neuropathy (gastroparesis, orthostatic hypotension or hypoglycemia unawareness).
• •Myocardial infarction or stroke within the preceding six (6) months.
• •Positive hepatitis B (HBsAg) or positive Human Immunodeficiency Virus (HIV) serology or active Hepatitis C (HepCAb) at screening.
• •History or presence of clinically significant cardiovascular, hepatic, gastrointestinal, neurological or infectious disorders capable of altering the absorption, metabolism or elimination of drugs, or constituting a significant risk factor when taking trial medication.
• •ALT or AST \> 3 times the upper limit of the normal reference range.
• •Anemia (hemoglobin levels \< 11 g/dL for females and \< 12 g/dL for males).
• •On-going respiratory infection.
• •Prior diagnosis of systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine
• •Pregnancy, lactation, or the intent of becoming pregnant during the trial period.
• •Women of childbearing potential practicing inadequate birth control (adequate birth control is defined as using oral contraceptives, condoms or diaphragms with spermicide, intrauterine devices, or surgical sterilization).
• •Current drug or alcohol abuse (regular alcohol intake \> 14 units/week), or history which in the opinion of the investigator would not make the subject a suitable candidate for participation in this trial. A unit of alcohol is defined as 8 g of ethanol, ¼ liter of beer or 1 glass of wine or 1 measure of spirits.
• •Investigator or site personnel directly affiliated with this trial, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.