Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00082407
First received: May 6, 2004
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

This is a Phase 3, multicenter, open-label, comparator-controlled trial comparing the effect of exenatide twice daily to twice daily biphasic insulin aspart on glycemic control, as measured by hemoglobin A1c (HbA1c).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: exenatide
Drug: biphasic insulin aspart
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: Efficacy of Exenatide (AC2993, Synthetic Exendin-4, LY2148568) Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in Glcosylated Hemoglobin (HbA1c) [ Time Frame: baseline, week 52 ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to week 52


Secondary Outcome Measures:
  • Percentage of Patients Achieving HbA1c <=7% [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 52 (percentage = [number of subjects with HbA1c <=7% at week 52 divided by number of subjects with HbA1c >7% at baseline] * 100%).

  • Change in Body Weight [ Time Frame: baseline, week 52 ] [ Designated as safety issue: No ]
    Change in body weight from baseline to week 52.

  • Change in Fasting Serum Glucose [ Time Frame: baseline, week 52 ] [ Designated as safety issue: No ]
    Change in fasting serum glucose from baseline to week 52

  • Change in 7-point Self-monitored Blood Glucose (SMBG) Profile [ Time Frame: baseline, week 52 ] [ Designated as safety issue: No ]
    Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52

  • Percentage of Patients With Hypoglycemic Events [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study

  • Change in Rate of Hypoglycemic Events [ Time Frame: baseline, week 52 ] [ Designated as safety issue: No ]
    Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52


Enrollment: 505
Study Start Date: November 2003
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Arm
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
Drug: exenatide
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
Other Name: Byetta
Active Comparator: Biphasic Insulin Aspart Arm
subcutaneous injection, twice daily; titration to target blood glucose level
Drug: biphasic insulin aspart
subcutaneous injection, twice daily; titration to target blood glucose level
Other Name: NovoLog

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 1. >=1500 mg/day immediate-release metformin or extended-release metformin and at least an optimally effective dose for brand of sulfonylurea, or 2. a fixed-dose sulfonylurea/metformin combination therapy with the same sulfonylurea and metformin requirements as for the individual components
  • HbA1c between 7.0% and 11.0%, inclusive.
  • Patients have a body mass index >25kg/m2 and <40 kg/m2.
  • Female patients are not breastfeeding, and female patients of childbearing potential test negative for pregnancy, do not intend to become pregnant during the study, and agree to continue using a reliable method of birth control

Exclusion Criteria:

  • Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study.
  • Patients are employed by Lilly or Amylin.
  • Patients have previously, in this or any other study, received exenatide or glucagon-like peptide-1 analogs.
  • Patients have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
  • Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
  • Patients have less than 5 years of remission history from any malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer).
  • Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
  • Patients have a known allergy or hypersensitivity to biphasic insulin aspart, exenatide, or excipients contained in these agents.
  • Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label.
  • Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.2 mg/dL for females.
  • Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase greater than three times the upper limit of the reference range.
  • Patients have known hemoglobinopathy or chronic anemia.
  • Patients have active proliferative retinopathy or macular edema.
  • Patients are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
  • Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
  • Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
  • Patients have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides.
  • Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
  • Patients fail to satisfy the investigator of suitability to participate for any other reason.
  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: NCT00082407

  Show 69 Study Locations
Sponsors and Collaborators
AstraZeneca
Eli Lilly and Company
Investigators
Study Director: Chief Medical Officer, MD Eli Lilly and Company
  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: NCT00082407     History of Changes
Other Study ID Numbers: H8O-MC-GWAD
Study First Received: May 6, 2004
Results First Received: July 16, 2009
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration
Croatia: Agency for Medicinal Product and Medical Devices
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: The Italian Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Slovenia: Agency for Medicinal Products - Ministry of Health
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
diabetes
exendin
Amylin
Lilly
insulin aspart

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

ClinicalTrials.gov processed this record on October 22, 2014