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

Phase 3

Completed

Conditions: Diabetes Mellitus

Interventions: Drug: Insulin Lispro
Drug: Exubera

Registration Number: NCT00348374

Lead Sponsor: Pfizer

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 191

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin Lispro	Insulin Lispro	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.
Exubera	Exubera	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at End of Treatment	Baseline, Week 24 (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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Each Visit	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	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.
Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) < 7.0%, < 6.5% and < 6.0% at Week 24	Week 24	Number of subjects acheiving glycemic control: HbA1c target levels of \<7.0%, \<6.5%, and \<6.0% at Week 24.
Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 12	Baseline, 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.
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	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.
Change From Baseline in Fasting and 2-hour Postprandial Glucose as Determined by 8-point Self-monitored Blood Glucose Profiles	Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	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.
Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 24	Baseline, 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.
Change From Baseline in Fasting and Postprandial Lipids as Determined by Standard Meal Tolerance Tests	Baseline, Week 12, Week 24	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.
Number of Subjects With Change From Baseline in Fasting and Postprandial Markers of Cardiovascular (CV) Risk as Determined by Standardized Meal Tolerance Tests	Week 12, Week 24	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.
Change From Baseline Weight at Each Visit	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	Change = mean body weight at observation minus mean body weight at Baseline.
Change From Baseline in Fasting Plasma Lipids	Baseline, Week 12, Week 24	Change from baseline in fasting plasma lipids at Week 12 and Week 24. Change = observation mean minus Baseline mean.
Change From Baseline in Insulin Glargine Dose at Each Visit (Office and/or Phone)	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	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 Prandial Insulin Dose (at Each Meal) at Each Visit	Week 0, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	Dose of inhaled insulin prior to each meal at each visit.
Number of Subjects With Hypoglycemic Events	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6	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.
Number of Total Hypoglycemic Events	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6	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.
Treatment Exposure for Hypoglycemic Subjects at Each Interval of the Study: Number of Subject Months of Treatment	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6	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.
Crude Hypoglycemic Event Rate	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6	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.
Change From Baseline in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire)	Week 4, 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 = mean Patient Satisfaction of Insulin Treatment (PSIT) score at observation minus mean score at Baseline.
Change in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire) From Week 4 to Week 24	Week 4, 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.
Change From Baseline in 24-hour Mean Glucose Values Measured by Continuous Glucose Monitoring System (CGMS)	Baseline, Week 12, Week 24	Mean of 24-hour Continuous Glucose Monitoring (CGMS) glucose values. Change from Baseline = mean at observation minus mean Baseline value.
Change From Baseline in Standard Deviation of 24-hour Glucose Values Measured by Continuous Glucose Monitoring System (CGMS)	Baseline, Week 12, Week 24	Mean change in standard deviation of all blood glucose values within 24-hour period. Change = mean at observation minus mean at Baseline.