Healthy Normal Volunteers Looking at Exposure and Effects of Multiple Doses of Technosphere® Insulin (TI) Using the Gen2C Inhaler

A Phase 1, Open-label, Randomized, Crossover Design Clinical Trial in Healthy Normal Volunteers to Evaluate Insulin Exposure and Effect Following Inhalation of Technosphere® Insulin Inhalation Powder at Multiple Doses Using the Gen2C Inhaler

This is an open-Label, Randomized Study in Healthy Normal Volunteers looking at exposure and effects (PK/PD) of multiple doses of Technosphere® Insulin (TI) using the Gen2C inhaler.

Healthy Normal Volunteers will be randomized to a sequence of 4 different doses of Technosphere® Insulin (TI), inhaled using the Gen2C device, and one dose of subcutaneously injected Regular Human Insulin. A euglycemic clamp procedure will be performed at each dosing visit. The purpose of this study is to determine the insulin dose proportionality/linearity of Technosphere® Insulin (TI) Inhalation Powder based on the AUCo-180 after administration of the following doses using the Gen2C inhaler:

• 10 U (one 10 U cartridge)
• 30 U (one 10 U and one 20 U cartridge)
• 60 U (three 20 U cartridges)
• 80 U (four 20 U cartridges)

Inclusion Criteria:

• Men and women aged 18 to 55 years who are considered healthy based on screening physical examination, medical history, clinical chemistry, and urinalysis
• Good venous access for blood draws
• No smoking in the previous 6 months (including cigarettes, cigars, pipes) and negative urine cotinine testing (< 100 ng/mL)
• Body mass index (BMI) < 32 kg/m2
• FEV1 = 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted
• FVC = 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted
• Written informed consent provided

Exclusion Criteria:

• Blood donation of 500 mL within the previous 56 days
• Fasting blood sugar >130 mg/dL
• History of coronary artery disease, peripheral vascular disease, or congestive heart failure
• Allergy to study drug, food, or other study material (eg, peanuts, soy products)
• Clinically significant active or chronic illness
• History of asthma, COPD, or any other clinically relevant chronic lung disease
• Respiratory tract infection within 4 weeks before screening
• Donation of blood within 3 months before screening
• History of drug or alcohol abuse
• Positive urine drug screen
• Clinically significant screening ECG, physical examination, laboratory test, or vital sign abnormality
• Any subject who, in the opinion of the PI or a designee, appears to not be qualified for this study
• Exposure to any other investigational drug or device within 30 days before treatment or within 90 days before treatment for drugs known to modify glucose metabolism (except metformin
• History of malignancy within the 5 years before screening (other than basal cell carcinoma)
• History of human immunodeficiency virus (HIV) infection or hepatitis B or C
• Women who are pregnant, lactating, or planning to become pregnant during the clinical study period
• Any subject who at Visit 2 has a blood glucose value = 150 mg/dL 2 hours after the meal, should be discussed with the MKC medical monitor and may be removed as potentially having impaired glucose tolerance
• Inability, in the opinion of the PI or a designee, to adequately inhale TI Inhalation Powder
• 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 the purposes of this clinical study includes experiencing amenorrhea for 2 or more years or being surgically sterile