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

Phase 2

Completed

• Conditions: Diabetes Mellitus: Type 1
• Interventions: Drug: RAA Population; Drug: Technosphere® Insulin Inhalation Powder; Drug: Technosphere Insulin® Inhalation Powder

• Registration Number: NCT00662857
• Lead Sponsor: Mannkind Corporation

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-04-16
• Study First Submitted QC: 2008-04-16
• Study First Posted: 2008-04-21
• Primary Completion: 2008-11
• Study Completion: 2008-12
• Disposition First Submitted: 2009-06-09
• Results First Submitted: 2014-07-22
• Status Verified: 2014-10
• Results First Submitted QC: 2014-10-09
• Disposition First Submitted QC: 2014-10-09
• Last Update Submitted: 2014-10-09
• Results First Posted: 2014-10-16
• Disposition First Posted: 2014-10-16
• Last Update Posted: 2014-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
3: RAA Population	RAA Population	Rapid Acting Analogue subjects received 10 IU sc Insulin Lispro
1: TI Inhalation Powder A	Technosphere® Insulin Inhalation Powder	Technosphere® Insulin Inhalation Powder, two 15 U cartridges
2: TI Inhalation Powder B	Technosphere Insulin® Inhalation Powder	Technosphere® Insulin Inhalation Powder, one 30 U cartridge

Primary Outcome Measures

Name	Time	Method
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	0 to 360 minutes post-dose	Dose-normalized baseline-corrected area under the serum insulin vs. time curve
Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro	0 to 360 minutes post-dose	Dose-normalized baseline-corrected area under the serum insulin vs. time curve (time 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
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.	0 to 360 minutes post-dose	Maximum observed baseline-corrected serum insulin concentration

Trial Locations

Locations (2)

Profil Institute for Clinical Research Inc.; 🇺🇸 Chula Vista, California, United States

Diabetes & Glandular Disease Research Assoc PA; 🇺🇸 San Antonio, Texas, United States