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 Phase 1b, Single-Dose, Open-Label, Parallel, Controlled Pharmacology Trial of Inhaled Technosphere®/Insulin in Non-Diabetic Subjects With COPD Versus Matched Non-Diabetic Subjects Without 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