A Study to Evaluate Insulin in the Blood After Inhalation of a Dry Powder Insulin Formulation (Called Technosphere®/Insulin) in Non-diabetic Patients With & Without Chronic Obstructive Pulmonary Disease (COPD)
A Study to Evaluate Insulin in the Blood After Inhalation of a Dry Powder Insulin Formulation (Called Technosphere®/Insulin) in Non-diabetic Patients With & Without Chronic Obstructive Pulmonary Disease (COPD)
Trial will include 40 subjects and consists of 3 visits: Screening, Treatment and Follow up.
 A euglycemic clamp procedure and Technosphere®/Insulin (T/I) administration will occur at
 Visit 2 for both COPD and non COPD subjects.
Trial objectives are to evaluate the impact of a defined lung disease (COPD) on
 pharmacokinetic parameters of insulin and fumaryl diketopiperazine (FDKP) after inhalation of
 Technosphere®/Insulin (T/I), the investigational medicinal product. 40 non diabetic subjects,
 20 COPD and 20 age/gender/BMI-matched non COPD subjects will participate in 3 visits: Visit 1
 (screening), Visit 2 (subjects will undergo a euglycemic clamp procedure and be dosed with
 T/I) and Visit 3 (follow up visit).
Inclusion Criteria:

 -  Male and female subjects minimum 18 and maximum 70 years of age

 -  Body Mass Index (BMI) = 36 kg/m2

 -  Subjects with COPD: Diagnosis of COPD (emphysema and/or chronic bronchitis),

 -  smoking history =10 years, chronic cough present intermittently or daily with or
 without sputum and/or dyspnea upon exertion.

 -  Subjects with COPD: Pulmonary Function Tests - FEV1 =50% (NHANES) III

 -  Predicted; FEV1/FVC < 70 % (NHANES) III; TLC =80% of Predicted (ITS) and DLco(unc)
 =50% of Predicted (Miller)

 -  Subjects without COPD: PFTs: FEV1 = 70% NHANES III Predicted; TLC =80% of

 -  Predicted (ITS) and DLco(unc) =80% of Predicted (Miller)

 Exclusion Criteria:

 -  History of pre-diabetes or diabetes

 -  Previous or current treatment with any anti-diabetic drugs

 -  Serum creatinine > 2.0 mg/dL in males and > 1.8 mg/dL in females

 -  Active smokers defined as having smoked their last cigarette, pipe, and/or cigar
 without the previous 6 months

 -  Previous exposure to any inhaled insulin product or investigational medicines/devices
 within the previous 30 days prior to entry or participation

 -  Clinically significant major organ disease

 -  Female subjects of childbearing potential not practicing adequate birth control

 -  Subjects with COPD: Significant improvement in pre-to post-bronchodilator spirometry
 (defined as an increase of 12% AND 200 mL in either FVC or FEV1);

 -  Any clinically important pulmonary disease except mild or moderate COPD

 -  Subjects without COPD: Any important pulmonary disease confirmed by pulmonary function
 testing and/or radiologic findings