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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin Lispro; Drug: Exubera

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-307
      • Pfizer Investigational Site
    • Mobile, Alabama, United States, 36608
      • Pfizer Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85006-2850
      • Pfizer Investigational Site
  • Arkansas
    • Malvern, Arkansas, United States, 72104
      • Pfizer Investigational Site
  • California
    • Foot Hill Ranch, California, United States, 92610
      • Pfizer Investigational Site
    • Fresno, California, United States, 93720
      • Pfizer Investigational Site
    • Greenbrae, California, United States, 94904
      • Pfizer Investigational Site
    • Los Gatos, California, United States, 95032-3739
      • Pfizer Investigational Site
    • San Diego, California, United States, 92120
      • Pfizer Investigational Site
    • San Mateo, California, United States, 94401-3805
      • Pfizer Investigational Site
    • Tustin, California, United States, 92780
      • Pfizer Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Pfizer Investigational Site
  • Connecticut
    • New Britain, Connecticut, United States, 06050
      • Pfizer Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2934
      • Pfizer Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Pfizer Investigational Site
    • Jacksonville, Florida, United States, 32205
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33156
      • Pfizer Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Pfizer Investigational Site
    • Winter Park, Florida, United States, 32789
      • Pfizer Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Pfizer Investigational Site
    • Decatur, Georgia, United States, 30034-1680
      • Pfizer Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pfizer Investigational Site
    • Honululu, Hawaii, United States, 96814
      • Pfizer Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Pfizer Investigational Site
    • Gurnee, Illinois, United States, 60031
      • Pfizer Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Pfizer Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40213
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21234-4607
      • Pfizer Investigational Site
    • Bethesda, Maryland, United States, 20817
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pfizer Investigational Site
  • Michigan
    • Flint, Michigan, United States, 48532
      • Pfizer Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454-1321
      • Pfizer Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Pfizer Investigational Site
  • New York
    • East Syracuse, New York, United States, 13057
      • Pfizer Investigational Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Pfizer Investigational Site
    • Morehead City, North Carolina, United States, 28557
      • Pfizer Investigational Site
    • Statesville, North Carolina, United States, 28625
      • Pfizer Investigational Site
  • Ohio
    • Kettering, Ohio, United States, 45429
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74104
      • Pfizer Investigational Site
  • Oregon
    • Bend, Oregon, United States, 97701
      • Pfizer Investigational Site
  • Pennsylvania
    • Bensalem, Pennsylvania, United States, 19020
      • Pfizer Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Pfizer Investigational Site
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • Pfizer Investigational Site
    • Memphis, Tennessee, United States, 38119
      • Pfizer Investigational Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Pfizer Investigational Site
    • Arlington, Texas, United States, 76014
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75230
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • El Paso, Texas, United States, 79935
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77004
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229
      • Pfizer Investigational Site
  • Vermont
    • Bennington, Vermont, United States, 05201-5018
      • Pfizer Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Pfizer Investigational Site
    • Virginia Beach, Virginia, United States, 23462
      • Pfizer Investigational Site
  • Washington
    • Renton, Washington, United States, 98055
      • Pfizer Investigational Site
    • Spokane, Washington, United States, 99208
      • Pfizer Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: 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.
Experimental: 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.	Drug: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: June 30, 2006
• First Submitted That Met QC Criteria: June 30, 2006
• First Posted (Estimate): July 4, 2006

Study Record Updates

• Last Update Posted (Estimate): March 16, 2010
• Last Update Submitted That Met QC Criteria: March 2, 2010
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: type two diabetes, insulin, HbA1c
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: A2171093