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

Study Overview
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Brief Summary
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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
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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)

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Technosphere Insulin Inhalation Powder using the Gen2C inhaler
* Drug: Regular Human Insulin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Regular Human Insulin<br>Subcutaneous injection | Drug: Regular Human Insulin<br>* Subcutaneous injection<br>|
| Experimental: TI and Regular Human Insulin<br>All subjects have 4 clamp procedures with 10, 30, 60,80 units of TI and 1 clamp with 15 IU Regular Human Insulin | Drug: Technosphere Insulin Inhalation Powder using the Gen2C inhaler<br>* Inhalation Powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | crossover 5 times over the course of up to 6 weeks | 
| Area-under-the-serum glucose infusion rate (GIR AUC0-240min) for TI compared to AUC0-600min for RHI | 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 | crossover 5 times over the course of up to 6 weeks | 
| Safety variables included adverse events (AEs), clinical laboratory tests, vital signs and physical examinations |  | crossover 5 times for up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, PD