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):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00097500
First received: November 24, 2004
Last updated: June 4, 2014
Last verified: June 2014
  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 AstraZeneca:

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
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: NCT00097500

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

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
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: June 4, 2014
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Sweden: Medical Products Agency

Keywords provided by AstraZeneca:
diabetes
exenatide
exendin-4
Amylin
Lilly

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

ClinicalTrials.gov processed this record on September 29, 2014