Healthy
Conditions
Keywords
PK, PD
Brief 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.
Detailed description
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)
Interventions
DRUGTechnosphere Insulin Inhalation Powder using the Gen2C inhaler
Inhalation Powder
Subcutaneous injection
Sponsors
Mannkind Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| area-under-the-serum insulin concentration versus time curve (AUC0-240min) for inhaled Technosphere Insulin (TI) post-dosing of a TI dose (10 U, 30 U, 60 U or 80U). Time points: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 and 240 minutes post-TI dosing | crossover 4 times over the course of up to 5 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area-under-the-serum insulin concentration versus time curve (AUC0-240min) for inhaled Technosphere Insulin (TI) compared to that of subcutaneous regular human insulin (RHI) | crossover 5 times over the course of up to 6 weeks | Timepoints: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 and 240 minutes after administration of TI dosing; 0, 15, 30, 60, 90, 120, 180, 240, 300, 360, 480 and 600 minutes after RHI dosing |
| Area-under-the-serum glucose infusion rate (GIR AUC0-240min) for TI compared to AUC0-600min for RHI | crossover 5 times over the course of up to 6 weeks | Timepoints for TI: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 and 240 minutes after TI dosing Timepoints: 0, 15, 30, 60, 90, 120, 180, 240, 300, 360, 480 and 600 minutes after RHI dosing |
| Safety variables included adverse events (AEs), clinical laboratory tests, vital signs and physical examinations | crossover 5 times for up to 6 weeks | — |
Countries
United States
Outcome results
None listed