Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00097500
First received: November 24, 2004
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

This Phase 3, open-label, multicenter study is designed to compare the effects of exenatide and insulin glargine (Lantus® injection) on beta-cell function in patients with type 2 diabetes mellitus using metformin.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: exenatide
Drug: Insulin glargine
Drug: Metformin
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 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects With Type 2 Diabetes Treated With Metformin Who Have Not Achieved Target HbA1c

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Beta-cell Function After 52 Weeks of Therapy [ Time Frame: Baseline (week -2) and 52 weeks ] [ Designated as safety issue: No ]
    Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]).


Secondary Outcome Measures:
  • Beta-cell Function 4 Weeks After Cessation of Therapy [ Time Frame: Baseline (week -2) and 56 weeks ] [ Designated as safety issue: No ]
    Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]).

  • Change in First Phase C-peptide Release [ Time Frame: baseline (week -2), 52 weeks, and 56 weeks ] [ Designated as safety issue: No ]
    Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure.

  • Change in Second Phase C-peptide Release [ Time Frame: baseline (-2 weeks), 52 weeks, and 56 weeks ] [ Designated as safety issue: No ]
    Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure.

  • Change in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Week 0 and week 52 ] [ Designated as safety issue: No ]
    Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).

  • Change in Fasting Plasma Glucose [ Time Frame: 0 weeks and 52 weeks ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0).

  • Seven Point Self Monitored Blood Glucose (SMBG) Measurements [ Time Frame: 0 weeks and 52 weeks ] [ Designated as safety issue: No ]
    SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).

  • Change in Body Weight [ Time Frame: 0 weeks and 52 weeks ] [ Designated as safety issue: No ]
    Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).

  • M-value at Baseline, Week 52 and Week 56 [ Time Frame: baseline (week -2), 52 weeks, and 56 weeks ] [ Designated as safety issue: No ]
    M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp.


Enrollment: 69
Study Start Date: September 2004
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Arm
Exenatide and Metformin
Drug: exenatide
subcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets
Other Name: Byetta
Drug: Metformin
Patients usual dosage
Active Comparator: Insulin Glargine Arm
Insulin Glargine and Metformin
Drug: Insulin glargine
subcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets
Other Name: Lantus
Drug: Metformin
Patients usual dosage

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of type 2 diabetes, but otherwise healthy
  • HbA1c between 6.6% and 9.5%, inclusive.
  • Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive.
  • Treated with a stable dose of metformin for at least 2 months prior to screening.

Exclusion Criteria:

  • Patients previously in a study using exenatide.
  • Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening).
  • Treated with insulin within 3 months of screening.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00097500

Locations
Finland
Research Site
Helsinki, Finland
Netherlands
Research Site
Amsterdam, Netherlands
Sweden
Research Site
Goteborg, Sweden
Sponsors and Collaborators
Bristol-Myers Squibb
Eli Lilly and Company
Investigators
Study Director: Vice President, Research and Development, MD Amylin Pharmaceuticals, LLC.
  More Information

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00097500     History of Changes
Other Study ID Numbers: 2993-114
Study First Received: November 24, 2004
Results First Received: December 24, 2010
Last Updated: October 31, 2013
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Sweden: Medical Products Agency

Keywords provided by Bristol-Myers Squibb:
diabetes
exenatide
exendin-4
Amylin
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Glargine
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014