Effect of Exenatide Plus Metformin vs. Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effect of Exenatide Plus Metformin vs. Premixed Human Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Inadequate Control of Type 2 Diabetes on Oral Antidiabetic Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00434954
• Other study ID #: H8O-SB-GWBN
• Status: Completed
• Phase: Phase 3
• First received: February 12, 2007
• Last updated: March 19, 2015
• Start date: February 2007
• Est. completion date: June 2009

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This study in Germany is designed to compare the effects of twice-daily exenatide plus metformin and twice-daily premixed human insulin aspart plus metformin with respect to glycemic control, as measured by HbA1c, combined with the percentage of patients with at least one treatment-emergent hypoglycemic episode. Patients will be treated with study therapy for approximately 26 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 494
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Have been treated with diet and exercise and a stable, maximally tolerated dose of immediate-release or extended-release metformin, or the combination of metformin (any dosage) with sulfonylurea/meglitinides for at least 3 months prior to study start

• Have not received thiazolidinediones, or alpha-glucosidase inhibitors for longer than 2 weeks within 3 months prior to study start, and have not received any insulin formulation for more than 14 days (other than in emergency situations) and within 14 days prior to study start

• Have an HbA1c between 6.5% and 10.0%, inclusive

• Have a body mass index (BMI) between 25 kg/m^2 and 40 kg/m^2, inclusive

Exclusion Criteria:

• Have type 1 diabetes or known latent autoimmune diabetes in adults

• Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks prior to study start

• Are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility (e.g., metoclopramide, cisapride, and chronic macrolide antibiotics)

• Have used any prescription drug to promote weight loss within 3 months prior to study start

• Have received treatment within 30 days prior to study start with a drug that has not received regulatory approval for any indication at the time of study entry

• Have previously completed or withdrawn from this study or any other study investigating exenatide or GLP-1 analogs

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
• Hypoglycemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide twice daily (BID)
subcutaneous injection (5 mcg or 10 mcg), twice a day
• premixed insulin aspart twice daily (BID)
subcutaneous injection (titrated appropriately), twice a day

Locations

Country	Name	City	State
Germany	Research Site	Bad Mergentheim
Germany	Research Site	Berlin
Germany	Research Site	Bosenheim
Germany	Research Site	Burghausen
Germany	Research Site	Datteln
Germany	Research Site	Dresden
Germany	Research Site	Essen
Germany	Research Site	Friedrichsthal
Germany	Research Site	Hildesheim
Germany	Research Site	Hirschhorn
Germany	Research Site	Hohenmolsen
Germany	Research Site	Jena
Germany	Research Site	Lehrte
Germany	Research Site	Leipzig
Germany	Research Site	Ludwigsburg
Germany	Research Site	Mannheim
Germany	Research Site	Marburg
Germany	Research Site	Marktheidenfeld
Germany	Research Site	Meissen
Germany	Research Site	Munchen
Germany	Research Site	Offenbach
Germany	Research Site	Oschatz
Germany	Research Site	Pohlheim
Germany	Research Site	Regensburg
Germany	Research Site	Riesa
Germany	Research Site	Rodgau
Germany	Research Site	Roding
Germany	Research Site	Rosenheim
Germany	Research Site	Schluchtern
Germany	Research Site	Schwedt/Oder
Germany	Research Site	Sinsheim
Germany	Research Site	Speyer
Germany	Research Site	Unterhaching
Germany	Research Site	Volklingen
Germany	Research Site	Wallerfing
Germany	Research Site	Wangen
Germany	Research Site	Warburg
Germany	Research Site	Wiesbaden
Germany	Research Site	Wolfsburg

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Hemoglobin (HbA1c)	Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)	Baseline and 26 weeks	No
Primary	Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)	Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26	26 weeks	No
Secondary	Percentage of Subjects Achieving HbA1c Target of < 6.5%	Percentage of subjects achieving HbA1c target of < 6.5% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 6.5% divided by total number of subjects times 100%].	26 weeks	No
Secondary	Percentage of Subjects Achieving HbA1c Target of < 7.0%	Percentage of subjects achieving HbA1c target of < 7.0% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 7.0% divided by total number of subjects times 100%].	26 weeks	No
Secondary	Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period)	Risk for the first hypoglycemic episode to occur up to Week 26 (percentage of subjects who experienced at least one treatment-emergent hypoglycemic episode during the 26-week treatment period)[ i.e., number of subjects experiencing at least one hypoglycemic episode divided by total number of subjects times 100%]	26 weeks	No
Secondary	Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)	Risk for first nocturnal (night-time) hypoglycemic episode to occur up to week 26 (percentage of subjects who experienced at least one episode of nocturnal hypoglycemia during the 26 week treatment period) [i.e., number of subjects who experienced nocturnal hypoglycemia divided by total number of subjects times 100%].	26 weeks	No
Secondary	7 Point Self-monitored Blood Glucose (SMBG) Profiles	7-point self-monitored blood glucose profiles at baseline and the end of the study, measured at 7 times during the day (pre-breakfast, 2 hours post-breakfast, pre-lunch, 2 hours post-lunch, pre-dinner, 2 hours post-dinner, and 3:00am).	Baseline and 26 weeks	No
Secondary	Blood Lipid Levels	Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), and triglyceride levels at baseline (week 0) and the end of the study (week 26)	Baseline and 26 weeks	No
Secondary	Change in Body Weight	Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0)	Baseline and 26 weeks	No
Secondary	Change in Body Mass Index (BMI)	Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0)	Baseline and 26 weeks	No
Secondary	Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)	Total DTSQ treatment satisfaction score at baseline (week 0) and after 26 weeks of treatment (LOCF). Total DTSQ treatment satisfaction score is derived as sum score of the individual components 1 and 4-8 of the DTSQ questionnaire. Each component is scored on a scale of 0 (worst case) to 6 (best case). Higher values represent higher treatment satisfaction.	Baseline and 26 weeks	No
Secondary	Patient Reported Outcomes: Quality of Life (SF-12)	SF-12 Physical and Mental Component Summary Scores at baseline (week 0) and after 26 weeks of treatment (LOCF). SF-12 Physical and Mental Component Summary Scores are normalized scores ranging from 0 (worst case) to 100 (best case), and are derived from responses to 12 questions. Scores > 50 indicate an above-average health status.	Baseline and 26 weeks	No