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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00348374
First received: June 30, 2006
Last updated: March 2, 2010
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Drug: Insulin Lispro
Drug: Exubera
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at End of Treatment [ Time Frame: Baseline, Week 24 (End of Treatment) ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Each Visit [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Number of subjects acheiving glycemic control: HbA1c target levels of <7.0%, <6.5%, and <6.0% at 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 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 ] [ Designated as safety issue: No ]
    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 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 ] [ Designated as safety issue: No ]
    Change = mean body weight at observation minus mean body weight at Baseline.

  • Change From Baseline in Fasting Plasma Lipids [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 ] [ Designated as safety issue: No ]
    Dose of inhaled insulin prior to each meal at each visit.

  • Number of Subjects With Hypoglycemic Events [ Time Frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 4, Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4, Week 24 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
    Mean change in standard deviation of all blood glucose values within 24-hour period. Change = mean at observation minus mean at Baseline.


Enrollment: 191
Study Start Date: June 2006
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00348374

  Show 63 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00348374     History of Changes
Other Study ID Numbers: A2171093
Study First Received: June 30, 2006
Results First Received: August 3, 2009
Last Updated: March 2, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
type two diabetes, insulin, HbA1c

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Insulin
Insulin Lispro
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014