Clinical trial NCT00662857: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus: Type 1
Keywords: Diabetic adult male, diabetic adult female
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2008-04-21
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 0 to 360 minutes post-dose
measure: 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.
timeFrame: 0 to 360 minutes post-dose
measure: 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
timeFrame: 0 to 360 minutes post-dose
measure: Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro
timeFrame: 0 to 360 minutes post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research Inc.
state: California
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Assoc PA
state: Texas
Study officials:
References: