Comparison of Technosphere Insulin Inhalation Powder & Subcutaneous Rapid-Acting Analog in Subjects With Type 1 Diabetes

Study Overview
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Brief Summary
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This is an Open-label, randomized study in Type 1 diabetics looking at exposure and response (PK/PD) of TI using GEN2C Inhaler versus rapid acting analog.

Detailed Description
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Subjects with Type 1 diabetes will be randomized to either one dose of TI inhaled using the Gen2C device, or one dose of subcutaneously injected Rapid Acting Analog (RAA) and crossed over. Crossover Sequences: Sequence #1: Period 1 - one 20 U cartridge of TI; Period 2 - 8 U of RAA Sequence #2: Period 1 - 8 U RAA; Period 2 - one 20 U cartridge of TI An euglycemic clamp procedure will be performed at each dosing visit. The purpose of this study is to characterize the pharmacokinetics (PK) of the one dose of TI Inhalation Powder using the Gen2C inhaler as compared to one dose of subcutaneous RAA.

Official Title
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A Phase 1, Single-center, Open-label, Randomized, Crossover Design Clinical Study in Subjects With Type 1 Diabetes Comparing Insulin Exposure & Response Following Inhalation of Technosphere Insulin Inhalation Powder Using the Gen2C Inhaler Vs Subcutaneous Rapid-Acting Analog

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Technosphere Insulin Inhalation Powder
* Drug: Rapid Acting Analog


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 to 60 years One of more daily sc insulin injections of any insulin type or insulin pump use Body mass index (BMI) = 30 kg/m2 Pulmonary function tests (PFTs) conducted at Visit 1: 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 Diagnosis of type 1 diabetes for at least 12 months Good venous access for blood draws Written informed consent provided No smoking in the previous 6 months (including cigarette, cigars, pipes) and negative urine cotinine testing (<100 ng/mL) C-peptide < 0.3 ng/mL Hemoglobin A1c (HbA1c) = 10.0% Exclusion Criteria: Total daily insulin requirement of = 1.4 U/kg body weight Serum creatinine = 2.0 mg/dL in men and > 1.8 mg/dL in women Blood donation of 500 mL within the previous 56 days Current treatment with pramlintide acetate or exenatide Unstable diabetes control and evidence of severe complications of diabetes (ie, autonomic neuropathy) History of chronic obstructive pulmonary disease (COPD) or asthma, or any other clinically important pulmonary disease confirmed by pulmonary function testing or radiologic findings Upper respiratory tract infection within 8 weeks before screening 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 drug or alcohol abuse Positive urine drug screen Clinically significant screening ECG, physical examination, laboratory test, or vital sign abnormality 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 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 Inability, in the opinion of the PI or a designee, to adequately inhale TI Inhalation Powder Any subject who, in the opinion of the PI or a designee, appears to not be qualified for this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: TI Inhalation Powder<br>Technosphere Insulin Inhalation Powder using the Gen2C inhaler | Drug: Technosphere Insulin Inhalation Powder<br>* Inhalation Powder using the Gen2C inhaler<br>* Other names: TI;|
| Active Comparator: RAA<br>Rapid Acting Analog | Drug: Rapid Acting Analog<br>* Subcutaneous Injection<br>* Other names: RAA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK measures for TI Inhalation Powder (20U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing |  | Crossover 1 time within 3 - 10 days | 
| PK measures for RAA (8U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing |  | Crossover 1 time within 3 - 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinations |  | Crossover 1 time within 3 - 10 days | 
| Area under serum glucose infusion rate (GIR AUC 0-360) for TI Inhalation Powder (20U) as measured by: GIR AUC 0-360 timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing |  | Crossover 1 time within 3 - 10 days | 
| Area under serum glucose infusion rate (GIR AUC 0-360) for RAA (8U) as measured by: GIR AUC 0-360 timepoints: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing |  | Crossover 1 time within 3 - 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Pharmacodynamics, Hyperglycemia, Insulin