healthy normal volunteers looking at exposure and effects of multiple doses of technosphere® insulin (ti) using the gen2c inhaler

Conditions: Healthy

Summary: 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)

Eligibility criteria:
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

Keywords: pk pd