Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes - Full Text View

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:

MedlinePlus related topics: Blood Sugar Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Insulin human Exenatide Insulin glargine

U.S. FDA Resources

Further study details as provided by Amylin Pharmaceuticals, LLC.:

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

Amylin Pharmaceuticals, LLC.

Eli Lilly and Company

Investigators

Study Director:

Vice President, Research and Development, MD

Amylin Pharmaceuticals, LLC.

More Information

No publications provided by Amylin Pharmaceuticals, LLC.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bunck MC, Cornér A, Eliasson B, Heine RJ, Shaginian RM, Taskinen MR, Smith U, Yki-Järvinen H, Diamant M. Effects of exenatide on measures of ?-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011 Sep;34(9):2041-7.

Bunck MC, Cornér A, Eliasson B, Heine RJ, Shaginian RM, Wu Y, Yan P, Smith U, Yki-Järvinen H, Diamant M, Taskinen MR. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis. 2010 Sep;212(1):223-9. Epub 2010 Apr 29.

Responsible Party:	Amylin Pharmaceuticals, LLC.
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:	April 29, 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 Amylin Pharmaceuticals, LLC.:

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 May 16, 2013