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”

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, will be either two 15U cartridges or one 30U cartridge. Visit 4 dosing will be a sc injection of 10IU of RAA.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Dose Comparison, Crossover Assignment, Bio-equivalence Study

Study Primary Completion Date: July 2008

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

Intervention(s) in this Clinical Trial

• Drug: Technosphere Insulin A
  • Inhalation Powder, two 15U cartridges
• Drug: Technosphere Insulin B
  • Inhalation Powder, one 30U cartridge
• Drug: Humalog
  • A single subcutaneous 10IU of Rapid Acting Analogue

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Technosphere Insulin Inhalation Powder

Primary Measures

• Insulin AUC0-360min for TIB and TIA (assessment of bioequivalence) Insulin AUC0-360min for TIB to RAA (assessment of relative bioavailability)
  • Time Frame: 6 hours
    Safety Issue?: No

Secondary Measures

• Additional PK parameters of serum insulin and FDKP
  • Time Frame: 6 hours
    Safety Issue?: No

Inclusion Criteria:

• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Mannkind Corporation

Overall Clinical Trial Officials and Contacts

Anders H Boss, MD, MFPM Study Director Mannkind Corpotation  

Overall Contact: MannKind Investigational Site 1-888-493-8622 

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00662857

Study ID Number: MKC-TI-116

ClinicalTrials.gov Identifier: NCT00662857

Health Authority: United States: Food and Drug Administration