A Phase 1, Open-Label, Controlled Clinical Trial to Determine the Pulmonary Residence Time of Insulin and Fumaryl Diketopiperazine, Utilizing Bronchoalveolar Lavage, After Administration of Technosphere® Insulin Inhalation Powder in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- TI Inhalation Powder
- Conditions
- Healthy Subjects
- Sponsor
- Mannkind Corporation
- Enrollment
- 13
- Locations
- 1
- Primary Endpoint
- Estimation of the amount of insulin in the lungs and amount of FDKP by analyzing BAL fluid, obtained by a flexible fiber optic bronchoscope at various time points after admin of TI Inhalation Powder.
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
Lavage fluid (BAL) is inserted into a lung lobe using a flexible bronchoscope. The fluid is aspirated out to remove any remaining TI. It's performed twice at specific time points in 12 healthy volunteers. BAL fluid will be analyzed for insulin and FDKP.
Detailed Description
Informed consent and eligibility occur at Screening. Dosing is at Visit 2. Blood glucose levels are monitored and adjusted using IV infusion of glucose. Bronchoalveolar lavage (BAL) is performed at 30 minutes and 6 hours for Cohort 1 and at 4 and 8 hours for Cohort 2, post TI dose. A series of blood samples are taken at specified timepoints. Cohort 3 will proceed with dosing if deemed necessary once analysis of BAL from Cohorts 1 \& 2 is performed. Visit 3 is the follow-up safety visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Nonsmokers for greater than or equal to 12 months
- •Normal chest x-ray (CXR) at Screening/Visit 1
- •Prebronchodilator FEV1 greater than or equal to 80% Third National Health and Nutrition Examination Survey (NHANES) III Predicted
- •Prebronchodilator FEV1/FVC greater than or equal to LLN% NHANES III Predicted
- •Prebronchodilator total lung capacity (TLC) greater than or equal to 80% of Predicted Intermountain Thoracic Society (ITS)
- •Prebronchodilator Dlco (unc) greater than or equal to 80% Predicted (Miller)
- •Written Informed Consent
Exclusion Criteria
- •History of diabetes mellitus
- •Previous exposure to TI Inhalation Powder within 3 months of Visit 1, or exposure to any other inhaled insulin product
- •Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the trial or a history of hypersensitivity to TI Inhalation Powder or to drugs with a similar chemical structure.
- •History of chronic obstructive pulmonary disease (COPD), asthma, and or any other clinically important pulmonary disease (eg, cystic fibrosis, bronchiectasis, and/or sleep apnea) confirmed by PFTs and/or radiologic findings.
- •Known allergic or adverse reactions to specified medications
- •Seizure disorder, significant cardiovascular dysfunction and/or history within 3 months of Visit 1, uncontrolled hypertension, known history of aortic or cerebral aneurysm, renal dysfunction or disease, serum creatinine \> 2.0 mg/dL in males and \> 1.8 mg/dL in females and/or blood urea nitrogen (BUN) \> 50 mg/dL
- •Cancer (other than excised cutaneous basal cell carcinoma) within the past 5 years or any history of lung neoplasms.
- •History of active viral and/or cirrhotic hepatic disease and/or abnormal liver enzymes, as evidenced by serum aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT) ? 3x upper limit of normal (ULN).
- •Active infection (eg, human immunodeficiency virus (HIV), hepatitis) or history of severe infection within 30 days of Visit 1
- •Anemia (hemoglobin value ? 10.5 g/dL for females or ? 11.5 g/dL for males.
Arms & Interventions
TI Inhalation Powder
TI Inhalation Powder, single dose, 60 units
Intervention: TI Inhalation Powder
Outcomes
Primary Outcomes
Estimation of the amount of insulin in the lungs and amount of FDKP by analyzing BAL fluid, obtained by a flexible fiber optic bronchoscope at various time points after admin of TI Inhalation Powder.
Time Frame: 2 Months