Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder)When an Optimal Dose is Taken With Varied Carbohydrate Intake

Study Overview
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Brief Summary
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The purpose of this study is to determine if, once a favorable dose of TI Inhalation Powder is established for either a type 1 or 2 patient, based on a average diabetic meal, the patient's favorable dose can be used safely, regardless of change in meal carbohydrate content. Patients were randomly assigned to various carbohydrate loads (0%, 50%, 100%, 150% or 200%). The 100% carbohydrate load was determined based upon their standard insulin dose for their normal meal.

Official Title
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A Phase 2, Single-Center, Open-Label, Pharmacodynamic Clinical Trial to Evaluate the Effect of Technosphere® Insulin Inhalation Powder Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) on Postprandial Glucose Levels in Subjects With Type 1 and Type 2 Diabetes Mellitus Ingesting Meals With Varied Carbohydrate Content

Conditions
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Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: TI Inhalation Powder and Humalog (Amendment 1)
* Drug: TI Inhalation Powder (original protocol)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnoses of type 1 or type 2 diabetes mellitus Fasting Plasma Glucose (FPG) 80, 140 mg/dL and glycated hemoglobin (A1C) > 6.5% and < or = 10.0%. Body mass index (BMI) of < or = 40 kg/m2 Non-smokers (never smoked or former smokers [= 6 months since cessation]) and a urine cotinine level < or = 100 ng/dL Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) Predicted; pre-bronchodilator FEV1 as a percentage of forced vital capacity (FEV1/Forced vital capacity(FVC)) = 70% For subjects with type 2 diabetes mellitus: Currently receiving oral diabetic treatment or basal insulin +/- oral diabetic treatment Exclusion Criteria: History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease confirmed by pulmonary function test (PFT) and/or radiologic findings Elevated liver function test (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times the normal reference range or bilirubin > 1.5 times the reference range) Previous use of Exubera; use of Symlin (pramlintide acetate) and/or Byetta (exenatide) within the past 12 weeks Unstable diabetes control and evidence of severe complications of diabetes mellitus (ie, autonomic neuropathy) Exposure to any investigational product(s) in the past 12 weeks For subjects with type 2 diabetes mellitus: In subjects taking metformin, serum creatinine > 1.4 mg/dL in female subjects and > 1.5 mg/dL in male subjects

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TI Inhalation Powder (original protocol)<br>Under the original protocol, subjects with Type 1 and Type 2 diabetes will have TI Inhalation Powder administered prandially during dose optimization visits and meal challenge visits (with meals of varying carbohydrate contents). Subjects with Type 2 diabetes will also use TI Inhalation Powder daily at each meal between visits. | Drug: TI Inhalation Powder (original protocol)<br>* Inhaled insulin technology to be administered immediately before a meal (prandially) for glucose control in Type 1 or Type 2 diabetics<br>|
| Other: TI Inhalation Powder and Humalog (Amendment 1)<br>Under Amendment 1, TI Inhalation Powder will be administered prandially to a new subset of subjects with Type 2 diabetes during TI dose optimization visits and TI meal challenge visits (with meals of varying carbohydrate contents). Subjects will be crossed over to administration of Humalog 15 minutes before meals during Humalog dose optimization visits and Humalog meal challenge visits (with meals of varying carbohydrate contents). Subjects will also use TI Inhalation Powder daily at each meal between visits. | Drug: TI Inhalation Powder and Humalog (Amendment 1)<br>* Subcutaneous (sc) rapid acting analog to be administered at one half of the meal challenge visits 15 minutes before a meal. Only the last 5 - 10 patients (Type 2) will be undergoing this amendment to the protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects) | AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC | 0 to 240 minutes | 
| Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects) | AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC | 0 to 240 minutes | 
| Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects) | AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC | 0 to 240 minutes | 
| Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects) | AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC | 0 to 240 minutes | 
| Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects) | Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch | 0 to 240 minutes | 
| Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects) | Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast | 0 to 240 minutes | 
| Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects) | Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch | 0 to 240 minutes | 
| Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects) | Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch | 0 to 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects) | Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch | 0 to 240 minutes | 
| Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects) | Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast | 0 to 240 minutes | 
| Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects) | Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch | 0 to 240 minutes | 
| Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects) | Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch | 0 to 240 minutes |