Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Inhalation Insulin (TI) Inhalation Powder Using the Gen2 Inhaler

Study Overview
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Brief Summary
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This is an open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of Technosphere Insulin (TI) Inhalation Powder in combination with insulin glargine versus insulin aspart in combination with insulin glargine in subjects with type 2 diabetes.

Detailed Description
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Phase 3 clinical trial is designed to examine the efficacy and safety of inhaled prandial TI Inhalation Powder in combination with basal insulin verses insulin aspart in combination with basal insulin in subjects with type 2 diabetes who are suboptimally controlled with their current insulin regimens.This trial will employ a variety of methods to intensively manage these subjects.

Official Title
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A Phase 3b, Multicenter, Open-label, Randomized, Forced-titration Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder, Using the Gen2 Inhaler, in Combination With Insulin Glargine Versus Insulin Aspart in Combination With Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Over a 16-week Treatment Period

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Technosphere® Insulin Inhalation Powder
* Drug: Insulin Aspart
* Drug: Insulin Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 and ≤ 80 years of age Clinical diagnosis of type 2 diabetes mellitus for more than 12 months Body mass index (BMI) ≤ 45 kg/m2 Glycated Hemoglobin (HbA1c) > 6.5% and ≤ 10.0% Treatment with 1 to 3 Oral Antidiabetic Drugs (OADs) and basal insulin for a minimum of 3 months before screening. Doses of OADs must have been stable for 3 months before study entry Nonsmokers (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding ≥ 6 months Office spirometry at the investigator site Forced expiratory volume in 1 second (FEV1) ≥ 65% Third National Health and Nutrition Examination Survey (NHANES III) predicted Forced vital capacity (FVC) ≥ 65% NHANES III predicted Forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1/FVC) ≥ lower limit of normal (LLN) Exclusion criteria: Current or prior treatment with prandial or PreMix (70/30) insulin History of insulin pump use within 6 weeks of Visit 1 Treatment with Glucagon-like Peptide (GLP-1) analog drugs within the preceding 12 weeks of Visit 1 History of chronic obstructive pulmonary disease (COPD), asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis) Any clinically significant radiological findings on screening chest x-ray Use of medications for asthma, COPD, or any other chronic respiratory conditions Evidence of serious complications of diabetes (eg, symptomatic autonomic neuropathy) Significant cardiovascular dysfunction or history within 3 months of Visit 1 (eg, congestive heart failure [New York Heart Association {NYHA} Class III or IV]) Serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or any cerebrovascular accident History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening (Visit 1)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Technosphere® Insulin Inhalation Powder (TI)<br>Insulin Glargine and Technosphere® Insulin Inhalation Powder | Drug: Technosphere® Insulin Inhalation Powder<br> <br> Drug: Insulin Glargine<br> <br> |
| Active Comparator: Comparator<br>Insulin Glargine and Insulin Aspart | Drug: Insulin Aspart<br>* Usual Care<br>Drug: Insulin Glargine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (%) From Baseline to Week 16 | Change from Baseline in glycated hemoglobin at Week 16 | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Effect of Each Treatment on HbA1c | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Comparison of Fasting Plasma Glucose (FPG) Levels at Randomization and Throughout the Study | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Comparison of Post-prandial Glucose (PPG) Levels at Randomization and Throughout the Study | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Glycomark and Fructosamine Levels Measured Throughout the Study | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Seven-point Glucose at Randomization and Throughout the Study | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Glycemic Excursions and Variability as Assessed Through Continuous Glucose Monitoring (CGM) | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Changes in Body Weight at 16 Weeks | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Treatment Satisfaction as Assessed by Subject Treatment and Health Outcomes Questionnaires | Not analyzed due to early termination of the trial. | Change from baseline to 16 weeks | 
| Total Number of Cough Episodes | Total number of times patients coughed once, intermittently or continuously (inclusive) | Baseline to Week 16 | 
| Severe Hypoglycemic Event Rate | Severe hypoglycemic event rate, ie, total number of events divided by subject-months of observation Severe hypoglycemia is defined as a subject who requires the assistance of another individual (not merely requested) and either: SMBG levels ≤ 36 mg/dL OR There is a prompt response to the administration of carbohydrate, glucagon, or other resuscitative measures | Baseline to Week 16 | 
| Mild or Moderate Hypoglycemic Event Rate | Mild or moderate hypoglycemic event rate, ie, total number of events divided by subject-months of observation Nonsevere hypoglycemia is defined as a subject: SMBG levels < 70 mg/dL AND/OR Symptoms that are relieved by the self-administration of carbohydrates | Baseline to Week 16 | 
| Number of Subjects Reporting Cough Episodes | Number of Subjects Reporting Cough Episodes | Baseline to Week 16 | 
| Number of Subjects Reporting Intermittent Coughing Episodes | Number of subjects reporting Intermittent Coughing Episodes | Baseline to Week 16 | 
| Number of Single Coughing Episodes | Total number of times patients coughed only once | Baseline to Week 16 | 
| Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation |  | Baseline to Week 16 | 
| Baseline Forced Expiratory Volume in 1 Second (FEV1) | Baseline FEV1 | Baseline | 
| Week 16 Forced Expiratory Volume in 1 Second | Week 16 FEV1 | Week 16 | 
| Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second | Week 16 Change from Baseline in FEV1 | Baseline to Week 16 | 
| Week 20 (Follow-up) Forced Expiratory Volume in 1 Second | Week 20 (Follow-up) FEV1, 4 weeks after discontinuation of study treatment | Week 20 (Follow-up) | 
| Week 20 (Follow-up) Change From Baseline in Forced Expiratory Volume in 1 Second | Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FEV1 | Baseline to Week 20 | 
| Baseline Forced Vital Capacity (FVC) | Baseline FVC | Baseline | 
| Week 16 Forced Vital Capacity | Week 16 FVC | Week 16 | 
| Week 16 Change From Baseline Forced Vital Capacity | Week 16 Change from Baseline FVC | Baseline to Week 16 | 
| Week 20 (Follow-up) Forced Vital Capacity | Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) FVC | Week 20 | 
| Week 20 (Follow-up) Change From Baseline in Forced Vital Capacity | Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FVC | Baseline to Week 20 |