A Study Designed to Compare 2 Dose Strengths of TI Inhalation Powder in Adults With Type 1 Diabetes Mellitus and to Compare One of Those Formulations (30Units) With an Injection of Insulin Lispro

Study Overview
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Brief Summary
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28 subjects to be enrolled for a screening period, 3 dosing visits & a follow-up visit. Visits 2 and 3 dosing of TI Inhalation Powder, cross over between two 15 U cartridges and one 30 U cartridge. Visit 4 dosing will be a sc injection of 10 IU of RAA (rapid-acting insulin analogue).

Detailed Description
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28 eligible subjects were planned to be enrolled to determine bioequivalence and safety parameters of two 15 U TI Inhalation Powder cartridges versus one 30 U TI Inhalation Powder cartridge, according to a randomized, 2-way crossover design. Additionally, bioavailability of one 30 U TI Inhalation Powder cartridge to a single subcutaneous injection of 10 IU of RAA will be compared.

Official Title
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A Phase 2, Open-Label, Randomized, 2-Way Crossover, Clinical Trial to Compare the Pharmacokinetics of 2 Formulations of Intended Commercial Product Technosphere® Insulin Inhalation Powder and to Determine the Bioavailability of a 30 Unit Cartridge of Intended Commercial Product Technosphere® Insulin Inhalation Powder Versus a 10 Unit Subcutaneous Injection of Insulin Lispro in Subjects With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus: Type 1

Intervention / Treatment
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* Drug: Technosphere® Insulin Inhalation Powder
* Drug: Technosphere Insulin® Inhalation Powder
* Drug: RAA Population


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females > 18 and < 60 years of age Clinical diagnosis of type 1 diabetes mellitus with stable anti-diabetic regimen for at least 90 days prior to Screening BMI of < 30 kg/m2 Non-smokers (never smoked or former smokers (> 6 months since cessation) Pulmonary Function Testing (FEV1 > 70%, FEV1/FVC > 70%, TLC > 80% DLco [unc] > 70% of Predicted Written Informed consent Exclusion Criteria: Two or more severe hypoglycemic episodes within 6 months of Screening/Visit 1 Severe complications of diabetes Previous exposure to any inhaled insulin product other than TI inhalation Powder or similar formulation Inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria Respiratory tract infection within 8 weeks prior to Screening/Visit 1 History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease (eg. Obstructive sleep apnea), confirmed by pulmonary function testing, and/or radiologic findings Major organ system diseases including seizures, heart failure, uncontrolled hypertension, cancer within the past 5 years, liver disease, anemia or autoimmune disorder Clinically significant abnormalities on screening laboratory evaluation Female subjects who are pregnant, lactating, or planning to become pregnant during the clinical trial period or not practicing adequate birth control Unable and/or unlikely to comprehend how to use the investigational device in this study or to follow study instructions

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: TI Inhalation Powder A<br>Technosphere® Insulin Inhalation Powder, two 15 U cartridges | Drug: Technosphere® Insulin Inhalation Powder<br>* TI Inhalation Powder, two 15 U cartridges<br>|
| Experimental: 2: TI Inhalation Powder B<br>Technosphere® Insulin Inhalation Powder, one 30 U cartridge | Drug: Technosphere Insulin® Inhalation Powder<br>* TI Inhalation Powder, one 30 U cartridge<br>|
| Experimental: 3: RAA Population<br>Rapid Acting Analogue subjects received 10 IU sc Insulin Lispro | Drug: RAA Population<br>* RAA Population: All subjects received a single 10 IU sc injection of insulin lispro.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence of Two 15 U Cartridges (TI Inhalation Powder A) and One 30 U Cartridge (TI Inhalation Powder B) Based on Baseline Corrected Insulin AUC0-360 | Dose-normalized baseline-corrected area under the serum insulin vs. time curve | 0 to 360 minutes post-dose | 
| Bioequivalence of Two 15 U Cartridges (TI Inhalation Powder A) and One 30 U Cartridge (TI Inhalation Powder B) Based on Baseline Corrected Insulin Cmax. | Maximum observed baseline-corrected serum insulin concentration | 0 to 360 minutes post-dose | 
| Bioequivalence of Two 15 U Cartridges (TI Inhalation Powder A) and One 30 U Cartridge (TI Inhalation Powder B) Based on Baseline Corrected Insulin Tmax |  | 0 to 360 minutes post-dose | 
| Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro | Dose-normalized baseline-corrected area under the serum insulin vs. time curve (time 0 to 360 minutes post-dose) | 0 to 360 minutes post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic adult male, diabetic adult female