Official Title: “A Phase 1, Open-Label Study to Investigate the Effect of Albuterol (Salbutamol) and Fluticasone on the Pharmacokinetics of Inhaled Technosphere® Insulin Inhalation Powder in Healthy Subjects”

This study will investigate the effects of inhaled albuterol & fluticasone on one dose of TI Inhalation Powder. A total of 12 eligible subjects will be enrolled.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study

Study Primary Completion Date: July 2008

Intervention(s) in this Clinical Trial

• Drug: Technosphere Insulin (TI) Inhalation Powder
  • 3.0 U of human insulin. 5 or 10 mg or Technosphere Inhalation Powder, containing 15 0r 30 U of insulin.
• Drug: Albuterol (Salbutamol)
  • 2 puff= 200ug total dose
• Drug: Fluticasone
  • 2 puffs= 500ug total dose

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1

Primary Measures

• PK parameters of serum insulin
  • Time Frame: 0-360 min
    Safety Issue?: No

Inclusion Criteria:

• Subjects must have a fasting blood glucose (BG) level of less than 6.1 mmol/L FEV1/ FVC =
• LLN TLC = 80% Predicted DLco (unc) = 80% Predicted (Miller) No significant improvement in pre- to post-bronchodilator spirometry (defined as an increase of = 12% and = 200 mL in FEV1 or FVC) at Screening FEV1 = 80% (NHANES III Predicted

Exclusion Criteria:

• History of diabetes mellitus Previous exposure to any inhaled insulin product Any known pulmonary disease or 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 Major organ system diseases including seizures, heart failure, uncontrolled hypertension, aneurysm, 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: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Mannkind Corporation

Overall Clinical Trial Officials and Contacts

Anders H. Boss Study Chair Mannkind Corporation  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00674050

Study ID Number: MKC-TI-114

ClinicalTrials.gov Identifier: NCT00674050

Health Authority: United States: Food and Drug Administration