This Study Is To Determine If Inhaled Insulin Is Effective In Treating Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This study is to determine if inhaled insulin is effective in treating type 2 diabetes mellitus.

Official Title
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A Six Month, Open Label, 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
* Drug: Inhaled Insulin (Exubera)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 30 years and ≤ 75 years with a diagnosis of type 2 diabetes mellitus made > 6 months prior to study entry Screening HbA1c > 7.0% Currently treated on a stable dose of at least 2 oral antidiabetic agents for at least 3 months prior to study entry; including a sulfonylurea and/or metformin, and/or a thiazolidinedione Exclusion Criteria: Smoking within last 6 months PFTs outside of range Type 1 diabetes mellitus Type 2 diabetes mellitus currently (last three months) treated with an insulin regimen (alone or with Oral Antidiabetic Agents) Active liver disease; significantly-impaired hepatic function, as shown by, but not limited to, alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate transaminase (AST) serum glutamic-oxaloacetic transaminase (SGOT) above 2x the upper limit of normal as measured at visit 1. However, patients with elevated ALT >1.5 upper limit of normal as a result of hepatic steatosis are permitted to enter the study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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<br>Insulin glargine, label instruction initiation dose (10 units), and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents. | Drug: Insulin glargine<br>* Insulin glargine, label instruction initiation dose (10 units), and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.<br>|
| Experimental: Exubera<br>Initiation dose of one mg per meal, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents. | Drug: Inhaled Insulin (Exubera)<br>* Initiation dose of one mg per meal, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral 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 A1c (HbA1c) at Week 26 for the Per Protocol (PP) Population | HbA1c lab value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26 | Percentage of subjects with glycosylated hemoglobin A1c lab value less than 6.5%. | Week 26 | 
| Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26 | Percentage of subjects with glycosylated hemoglobin A1c lab value less than 7.0%. | Week 26 | 
| Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26 | Number of subjects with glycosylated hemoglobin A1c lab value less than 8.0%. | Week 26 | 
| Change From Baseline in Fasting Plasma Glucose at Week 26 | Fasting plasma glucose lab value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Postprandial blood glucose lab value (Time 0 min [fasting], Time 30 min, Time 60 min, Time 90 min, Time 120 min, Time 180 min): Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-prandial=after a meal. 8-point scale: (1 = before breakfast, 2 = 2 hours post breakfast, 3 = before lunch, 4 = 2 hours post lunch, 5 = before dinner, 6 = 2 hours post dinner, 7 = at bedtime, 8 = overnight [between 2 and 4 am]). Postprandial blood glucose lab value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Lipids at Week 26 | Lipid (total cholesterol, high density lipoprotein cholesterol [HDL-c], low density lipoprotein cholesterol [LDL-c], triglycerides) lab value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | CV biomarker (hs-CRP, Leptin, and Spot Urine Microalbumin) lab value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 | CV biomarker (adiponectin and ApoB) lab value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26 | 24-Hour CGMS glucose lab value was obtained using the Medtronic MiniMed CGMS. Not all subjects were offered the opportunity to participate in this assessment. Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Mean Standard Deviation (SD) of 24-Hour Glucose Values Measured by CGMS at Week 26 | SD of 24-Hour CGMS glucose lab value obtained using the Medtronic MiniMed CGMS. Not all subjects were offered the opportunity to participate in this assessment. Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Number of Subjects With Hypoglycemic Events | A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. An event was severe if the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of < = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. | Months 1 to 7 | 
| Number of Total Hypoglycemic Events | A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of < = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. Total=events during the study. | Months 1 to 7 | 
| Number of Total Subject Months of Treatment | Number of total subject months of treatment. Subject months = number of days from start of treatment to the last day of active treatment + 1 day lag, including off-drug time)/30.44. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of < = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. | Months 1 to 7 | 
| Crude Hypoglycemic Event Rate | crude event rate=(events)/(subject-months). Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of < = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. | Months 1 to 7 | 
| Number of Nocturnal Hypoglycemic Events | A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of < = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Nocturnal hypoglycemia=event occuring from midnight to 5:59 am. | Months 1 to 7 | 
| Change From Baseline in Body Weight at Week 26 | Body weight value: Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Body Mass Index (BMI) at Week 26 | BMI value (kg/m2): Change = value at Week 26 minus value at Baseline. | Baseline, Week 26 | 
| Change From Baseline in Diabetes Treatment Satisfaction Questionnaire-Status, Diabetes Treatment Satisfaction Questionnaire-Change, Diabetes-39, Mental Health Inventory-17, and SF-36 Vitality Domain Questionnaire | Due to cancellation of the EXUBERA program, the collected Patient Reported Outcome (PRO) data, including the Diabetes Treatment Satisfaction Questionnaire-Status, Diabetes Treatment Satisfaction Questionnaire-Change, Diabetes-39, Mental Health Inventory-17, and SF-36 vitality domain questionnaire were not summarized, and no statistical analyses were performed. | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin Glargine Diabetes HbA1c