Exubera vs Lispro in a Lantus-based Regimen for Improved Glycemic Control in Type 2 Diabetes

Study Overview
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Brief Summary
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The current trial will examine the efficacy and safety of Exubera administered as a mealtime insulin compared to lispro, when added to an existing regimen of basal insulin glargine + or = Oral Agents (OAs). Dose titrations will be provided which should allow a large proportion of subjects to reach target glycosylated hemoglobin (A1C) levels.

Official Title
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A Phase 3b, Randomized, Open-Label, Parallel Group, Multicenter Trial Assessing The Efficacy Of Exubera Vs. Lispro Introduced Into A Lantus Based Regimen In Suboptimally Controlled Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Lispro
* Drug: Exubera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with type 2 diabetes using Lantus® (insulin glargine) as their basal insulin, not at glycemic goal. Exclusion Criteria: lung disease current smoking or discontinued smoking within past 6 months

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 |
| --- | --- |
| Active Comparator: Insulin Lispro<br>Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents. | Drug: Insulin Lispro<br>* Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents.<br>|
| Experimental: Exubera<br>Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents. | Drug: Exubera<br>* Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and 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 End of Treatment | Change from Baseline in glycosylated hemoglobin A1c (HbA1c %) at Week 24. Change = mean value at Week 24 minus mean value at Baseline. | Baseline, Week 24 (End of Treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Each Visit | Change in mean glycosylated hemoglobin A1c (HbA1c %) from Baseline to each visit through Week 24. Change = mean value at observation minus mean value at Baseline. | Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | 
| Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) < 7.0%, < 6.5% and < 6.0% at Week 24 | Number of subjects acheiving glycemic control: HbA1c target levels of <7.0%, <6.5%, and <6.0% at Week 24. | Week 24 | 
| Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) Target Levels of <7%, < 6.5%, and < 6.0% Without an Episode of Severe Hypoglycemia at Week 24 | Number of subjects that attained HbA1c target levels of <7%, < 6.5%,and <6.0% at Week 24 without an episode of severe hypoglycemia. | Week 24 | 
| Change From Baseline in Fasting and 2-hour Postprandial Glucose as Determined by 8-point Self-monitored Blood Glucose Profiles | Mean change from Baseline in fasting and 2-hour postprandial glucose at each visit in 8-point self-monitored blood glucose (SMBG) profiles: includes values prior to each meal (breakfast, lunch and dinner), 2 hours after each meal, at bedtime, and at 2:00 ante meridiem (a.m.) Change=observation value minus Baseline value. | Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | 
| Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 12 | Change from Baseine in fasting and postprandial plasma glucose as determined by standardized meal tolerance tests (MTT). Change = mean value at Week 12 minus mean value at Baseline. Time 0 results are for MTT (time 0) and non MTT (implied time 0) subjects. | Baseline, Week 12 | 
| Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 24 | Change from Baseline in fasting and postprandial plasma glucose as determined by standardized meal tolerance tests (MTT). Change = mean value at Week 24 minus mean value at Baseline. Time 0 results are for MTT (time 0) and non MTT (implied time 0) subjects. | Baseline, Week 24 | 
| Change From Baseline in Fasting and Postprandial Lipids as Determined by Standard Meal Tolerance Tests | Change from Baseline in fasting and postprandial lipids at Week 12 and Week 24 as determined by standard meal tolerance tests. Change = value at observation minus value at Baseline. Postprandial = 120 mins after meal. | Baseline, Week 12, Week 24 | 
| Number of Subjects With Change From Baseline in Fasting and Postprandial Markers of Cardiovascular (CV) Risk as Determined by Standardized Meal Tolerance Tests | Cardiovascular risk markers included serum high-sensitivity C-reactive protein (hs-CRP)[mg/L], leptin (ng/mL), adiponectin (ug/mL), and spot urine microalbumin. Change = observation of mean fasting and postprandial markers of cardiovascular risk at Week 12 and Week 24 minus mean Baseline observation. | Week 12, Week 24 | 
| Change From Baseline Weight at Each Visit | Change = mean body weight at observation minus mean body weight at Baseline. | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | 
| Change From Baseline in Fasting Plasma Lipids | Change from baseline in fasting plasma lipids at Week 12 and Week 24. Change = observation mean minus Baseline mean. | Baseline, Week 12, Week 24 | 
| Change From Baseline in Insulin Glargine Dose at Each Visit (Office and/or Phone) | Change from Baseline in insulin glargine at each visit. Change = mean at observation minus mean Baseline observation. Basal dose = injection of basal insulin (IU) (insulin glargine). | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | 
| Baseline Prandial Insulin Dose (at Each Meal) at Each Visit | Dose of inhaled insulin prior to each meal at each visit. | Week 0, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 | 
| Number of Subjects With Hypoglycemic Events | Severe event = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable/irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or not measured but clinical manifestations reversed by oral carbohydrates or glucose. Non-severe events = events that were mild-moderate. | Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 | 
| Number of Total Hypoglycemic Events | Total number and severity of hypoglycemic events. Severe events = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable or irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or not measured but clinical manifestations reversed by oral carbohydrates or glucose. Non-severe events = events that were mild or moderate. | Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 | 
| Treatment Exposure for Hypoglycemic Subjects at Each Interval of the Study: Number of Subject Months of Treatment | Subject months of treatment = number of days from start of treatment to last day of active treatment + 1 day lag (total number of subjects treated * days treated), including off-drug time)/30.44. Severity: severe = subject unable to treat self, had at least 1 neurological symptom (memory loss, confusion, uncontrollable/irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams/deciliter; or not measured but clinical manifestations were reversed by oral carbohydrates or glucose. Non-severe events = events that were mild or moderate. | Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 | 
| Crude Hypoglycemic Event Rate | Crude event rate = (number of events)/(subject months); severe hypoglycemic events: crude event rate = (number of events)/(100 subject months). Severe = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable or irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or unmeasured but clinical manifestestation reversed by oral carbohydrates or glucose. Non-severe events = mild-moderate. | Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 | 
| Change From Baseline in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire) | Patient Satisfaction with insulin treatment Questionnaire (PSIT): 15-item self administered questionnaire that measures global satisfaction and two domains (subscales): convenience/ease of use and social comfort in people with type 1 and type 2 diabetes. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). The scoring of responses to each item is analyzed so that a higher item score indicates more satisfaction. Change = mean Patient Satisfaction of Insulin Treatment (PSIT) score at observation minus mean score at Baseline. | Week 4, Week 24 | 
| Change in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire) From Week 4 to Week 24 | Patient Satisfaction with insulin treatment Questionnaire (PSIT): 15-item self administered questionnaire that measures global satisfaction and two domains (subscales): convenience/ease of use and social comfort in people with type 1 and type 2 diabetes. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). The scoring of responses to each item is analyzed so that a higher item score indicates more satisfaction. Change = difference in mean Patient Satisfaction with Insulin Treatment (PSIT) score from Week 4 to Week 24. | Week 4, Week 24 | 
| Change From Baseline in 24-hour Mean Glucose Values Measured by Continuous Glucose Monitoring System (CGMS) | Mean of 24-hour Continuous Glucose Monitoring (CGMS) glucose values. Change from Baseline = mean at observation minus mean Baseline value. | Baseline, Week 12, Week 24 | 
| Change From Baseline in Standard Deviation of 24-hour Glucose Values Measured by Continuous Glucose Monitoring System (CGMS) | Mean change in standard deviation of all blood glucose values within 24-hour period. Change = mean at observation minus mean at Baseline. | Baseline, Week 12, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type two diabetes, insulin, HbA1c