A Clinical Trial Comparing the Efficacy and Safety of Exubera® and Lantus®

Study Overview
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Brief Summary
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To compare efficacy and safety of Exubera® vs Lantus® in patients with type 2 diabetes mellitus.

Official Title
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A Six Month, Open-Label Outpatient, Randomized Parallel Group Trial Assessing The Impact Of Dry Powder Inhaled Insulin (Exubera®) On Glycemic Control Compared To Insulin Glargine (Lantus®) In Patients With Type 2 Diabetes Mellitus Who Are Poorly Controlled On A Combination Of Two Or More Oral Agents

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Glargine (Lantus®)
* Drug: Inhaled Human Insulin (Exubera®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes Mellitus, Type 2 on oral agents Age > 30 years Exclusion Criteria: Severe Asthma, severe Chronic Obstructive Pulmonary Disease Smoking

Ages Eligible for Study
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Minimum Age: 30 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 |
| --- | --- |
| Active Comparator: Insulin Glargine (Lantus®)<br> | Drug: Insulin Glargine (Lantus®)<br>* Patient will be randomized to Lantus® while remaining on pre-study oral hypoglycemic agents.<br>|
| Active Comparator: Inhaled Human Insulin (Exubera®)<br> | Drug: Inhaled Human Insulin (Exubera®)<br>* Patient will be randomized inhaled insulin while remaining on pre-study oral hypoglycemic agents.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | Change (measured as percent): HbA1c at observation minus HbA1c at baseline. Primary objective to demonstrate non-inferiority of inhaled insulin compared to insulin glargine for glycemic control after 26 weeks of treatment not attainable due to early termination of study; analyses were descriptive and graphical. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c Prior to Week 26 | Change (measured as percent) from baseline calculated as HbA1c at observation minus HbA1c at baseline. | Baseline, Week 2, Week 4, Week 8, Week 12, and Week 18 | 
| Number of Subjects With HbA1c < 6.5 % | Number of subjects with glycemic control HbA1c measurement of < 6.5 % at observation. | Week 26 | 
| Number of Subjects With HbA1c < 7.0 % | Number of subjects with glycemic control HbA1c measurement of < 7.0 % at observation. | Week 26 | 
| Number of Subjects With HbA1c < 8.0 % | Number of subjects with glycemic control HbA1c measurement of < 8.0 % at observation. | Week 26 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) Level | FPG measured as milligrams/deciliter (mg/dl). Change from baseline calculated as FPG at observation minus FPG at baseline. | Baseline, Week 26 | 
| Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point) | Blood glucose (BG) self-monitored by subject at home; measured at least once between Visits 2, 3 and between Visits 8, 9 (8-point: fasting, pre-meal, post-meal, bedtime, 2:00 am); between each visit: Visit 3 to 8 (7-point: fasting, post-meal, pre-lunch, pre-dinner, bedtime). Post-meal: 2-hour period after breakfast, lunch, dinner. Change: average overall absolute, pre-meal, and post-meal blood glucose = HBGM at observation minus HBGM at baseline; pre-meal to post-meal blood glucose = HBGM at post-meal minus HBGM at pre-meal. | Baseline, Week 26 | 
| Number of Subjects With Hypoglycemic Events by Severity | Number of subjects with hypoglycemic events by severity. Severe hypoglycemia: subject unable to treat self; exhibits a neurological symptom; and blood glucose <=2.72 mmol/L or blood glucose not measured but symptoms reversed with food intake, SC glucagon, or intravenous glucose. If all 3 criteria not met, hypoglycemia defined as mild or moderate. | Week 26 | 
| Number of Events of Nocturnal Hypoglycemia | Number of events of nocturnal hypoglycemia, incidence: midnight to 6:00 am. Hypoglycemia: characteristic symptoms of hypoglycemia with no blood glucose check; resolved with food intake, SC glucagon, or intravenous (IV) glucose; or symptoms with glucose <3.27 mmol/L (59 mg/dL); or any glucose measurement <=2.72 mmol/L (49 mg/dl). Severity of nocturnal glycemia not summarized. | Week 26 | 
| Change From Baseline in Body Weight | Change from baseline calculated as body weight at observation minus body weight at baseline. | Baseline, Week 26 | 
| Change From Baseline in Body Mass Index (BMI) | BMI measured as kilograms per meter squared (kg/m2). Change calculated as BMI at observation minus BMI at baseline. | Baseline, Week 26 | 
| Number of Subjects Discontinued Due to Insufficient Clinical Response | Number of subjects discontinued due to signs and symptoms of persistent hyperglycemia or HbA1c > 12.0 % or frequent and unexplained severe hypoglycemic events (> 3 events per month for 2 or more months); subject's HbA1c not < = 7 % at Week 12. | Week 26 | 
| Change From Baseline in Treatment Satisfaction, Quality of Life, and Mental Health | Subject reported outcomes for Diabetes Treatment Satisfaction Questionnaire-Status (DTSQs), DTSQ-change, Patient Satisfaction with Insulin Therapy-16 item, Mental Health Inventory-17 item, and Euro Quality of life 5-Dimensions (EuroQol 5-D) Questionnaire not summarized due to cancellation of Exubera® program. | Week 26 | 
| Continuous Glucose Monitoring System (CGMS) 24-hour Glucose Profile in a Subset of Patients | The mean of the 24-hour mean and the mean of the 24-hour standard deviation (SD) (variability around the average glucose concentration) calculated on glucose values (mg/dl) collected during inpatient evaluation of glycemic stability. Interstitial glucose assessed at 5 minute intervals starting pre-supper on Day 1 of evaluation; ending on Day 3 pre-breakfast. Analysis is on data generated between 6:00 am on Day 2 and 6:00 am on Day 3. | Baseline, Week 26 | 
| Change From Baseline in Cardiovascular (CV) Biomarkers - High Sensitive C-reactive Protein (Hs-CRP) | Change from baseline in CV biomarker hs-CRP (milligrams per deciliter [mg/dl]) calculated as hs-CRP at observation minus hs-CRP at baseline. | Baseline, Week 26 | 
| Change From Baseline in CV Biomarkers - Interleukin 6 (IL-6) | Change from baseline in IL-6 (picograms per milliliter [pg/ml]) calculated as IL-6 at observation minus IL-6 at baseline. | Baseline, Week 26 | 
| Change From Baseline in CV Biomarkers - Thrombin-antithrombin Complexes (Tat-complexes) | Change from baseline in tat-complexes (nanograms per milliliter [ng/ml]) calculated as tat-complexes at observation minus tat-complexes at baseline. | Baseline, Week 26 | 
| Change From Baseline in CV Biomarkers - Soluble Tissue Factor (STF) | Change from baseline in soluble tissue factor (pg/ml) calculated as STF at observation minus STF at baseline. | Baseline, Week 26 | 
| Change From Baseline in Urinary Free 8-iso Prostaglandin F2-alpha (α) in a Subset of Subjects | Urinary free 8-iso prostaglandin F2-alpha (α): compare glucose fluctuations and activation of oxidative stress as assessed by urinary isoprostanes in a subset of subjects randomized to either Exubera® or subcutaneous insulin glargine. The substudy was offered to all subjects. Data not summarized due to cancellation of Exubera® program. | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, insulin, glycemic control