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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00097500
• Other study ID #: 2993-114
• Status: Completed
• Phase: Phase 3
• First received: November 24, 2004
• Last updated: March 19, 2015
• Start date: September 2004
• Est. completion date: December 2009

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFinland: Finnish Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide
subcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets
• Insulin glargine
subcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets
• Metformin
Patients usual dosage

Locations

Country	Name	City	State
Finland	Research Site	Helsinki
Netherlands	Research Site	Amsterdam
Sweden	Research Site	Goteborg

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

Finland,  Netherlands,  Sweden, 

References & Publications (1)

Bunck MC, Diamant M, Cornér A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Järvinen H, Heine RJ. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated typ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beta-cell Function After 52 Weeks of Therapy	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]).	Baseline (week -2) and 52 weeks	No
Secondary	Beta-cell Function 4 Weeks After Cessation of Therapy	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]).	Baseline (week -2) and 56 weeks	No
Secondary	Change in First Phase C-peptide Release	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.	baseline (week -2), 52 weeks, and 56 weeks	No
Secondary	Change in Second Phase C-peptide Release	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.	baseline (-2 weeks), 52 weeks, and 56 weeks	No
Secondary	Change in Glycosylated Hemoglobin (HbA1c)	Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).	Week 0 and week 52	No
Secondary	Change in Fasting Plasma Glucose	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).	0 weeks and 52 weeks	No
Secondary	Seven Point Self Monitored Blood Glucose (SMBG) Measurements	SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).	0 weeks and 52 weeks	No
Secondary	Change in Body Weight	Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).	0 weeks and 52 weeks	No
Secondary	M-value at Baseline, Week 52 and Week 56	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.	baseline (week -2), 52 weeks, and 56 weeks	No