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

Sponsor:	Amylin Pharmaceuticals, Inc.
Collaborator:	Eli Lilly and Company
Information provided by:	Amylin Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00434954

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: exenatide twice daily (BID) Drug: premixed insulin aspart twice daily (BID)	Phase III

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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Hypoglycemia

Drug Information available for: Insulin Insulin beef Insulin aspart Exenatide Metformin Metformin hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Change in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)
Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26

Secondary Outcome Measures:

Percentage of Subjects Achieving HbA1c Target of < 6.5% [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
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%].
Percentage of Subjects Achieving HbA1c Target of < 7.0% [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
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%].
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) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
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%]
Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
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%].
7 Point Self-monitored Blood Glucose (SMBG) Profiles [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
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).
Blood Lipid Levels [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
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)
Change in Body Weight [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0)
Change in Body Mass Index (BMI) [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0)
Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ) [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
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.
Patient Reported Outcomes: Quality of Life (SF-12) [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
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.

Enrollment:	494
Study Start Date:	February 2007
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Exenatide Twice Daily (BID)	Drug: exenatide twice daily (BID) subcutaneous injection (5 mcg or 10 mcg), twice a day Other Name: Byetta
Active Comparator: Premixed Insulin Aspart Twice Daily (BID)	Drug: premixed insulin aspart twice daily (BID) subcutaneous injection (titrated appropriately), twice a day

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00434954

Locations

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

Sponsors and Collaborators

Amylin Pharmaceuticals, Inc.

Eli Lilly and Company

Investigators

Study Director:

Chief Medical Officer, MD

Eli Lilly and Company

More Information

No publications provided by Amylin Pharmaceuticals, Inc.

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

Gallwitz B, Böhmer M, Segiet T, Mölle A, Milek K, Becker B, Helsberg K, Petto H, Peters N, Bachmann O. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011 Mar;34(3):604-6. Epub 2011 Feb 1.

Responsible Party:	Chief Medical Officer, MD, Study Director, Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00434954 History of Changes
Other Study ID Numbers:	H8O-SB-GWBN
Study First Received:	February 12, 2007
Results First Received:	June 25, 2010
Last Updated:	July 30, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Amylin Pharmaceuticals, Inc.:

diabetes
exenatide
Byetta
Amylin
Lilly

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin aspart

Exenatide
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012