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This study will compare the rate and extent of absorption of TI Inhalation Powder in subjects with asthma and subjects with normal lung function. 24 eligible subjects will be enrolled into the treatment phase of the trial.
Visit 1 screening will determine eligibility and obtain informed consent. At visit 2, 3 and 4 subjects inhale 1 dose of 45U TI Inhalation Powder. At visit 3 subjects inhale 2 puffs (200mcg) Albuterol prior to dosing. Only asthmatic subjects undergo visit 4 where a methacholine challenge test (MCT) is performed followed by inhalation of Albuterol then administration of TI Inhalation Powder. Each visit's dosing will occur during a hyperinsulinemic euglycemic clamp. Visit 5 is the follow up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Technosphere Insulin Inhalation Powder | Drug | 3.0 of human insulin. single dose cartridges filled with 5 or 10 mg of Technosphere Inhalation Powder, containing 15 or 30 u of insulin |
| Measure | Description | Time Frame |
|---|---|---|
| AUCF 0-360 min of serum insulin | 0-360 min |
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Inclusion Criteria:
Non smoking male and female subjects = 18 and = 55 years of age with BMI = 34 kg/m2 Fasting blood glucose (FBG) < 110 mg/dL (6.1 mmol/L). Written informed consent Asthmatic Subjects: Clinical diagnosis of asthma along with defined reversibility from pre- to post-bronchodilator spirometry.
Pulmonary Function Testing for Asthmatic subjects: FEV1 > 70% (NHANES III), TLC >70% (ITS), Dlco >80% (Miller) Non-asthmatic healthy subjects: FEV1 > 80% (NHANES III), FEV1/FVC > LLN (NHANES), TLC >80% (ITS), Dlco >80% (Miller), no significant improvement from pre- to post-bronchodilator spirometry.
Exclusion Criteria:
Unable and/or unlikely to comprehend how to use the investigational device in this study or to follow study instructions Change in asthma therapeutic regimen from Screening through visit 5 Exacerbation of asthma within 8 weeks prior to Screening History of diabetes mellitus 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 Any clinically important pulmonary disease Major organ system diseases including seizures, heart failure, uncontrolled hypertension, cancer within the past 5 years, aneurysm, 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
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| Name | Affiliation | Role |
|---|---|---|
| Anders H. Boss | Mannkind Corporation | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medicines Evaluation Unit (MEU) | Manchester | England | M23 9QZ | United Kingdom | ||
| ICON Development Solutions |
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| Salbutamol (Albuterol) | Drug | 2 puff = 200 mcg total dose |
|
| Methacholine chloride | Drug | 5mls of methacholine; diluent sodium chloride 0.9%; formulation methacholine chloride in sodium chloride 0.9% |
|
| Manchester |
| M15 6SH |
| United Kingdom |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000420 | Albuterol |
| D016210 | Methacholine Chloride |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D008688 | Methacholine Compounds |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D009861 | Onium Compounds |
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