Safety and Efficacy of Exenatide as Monotherapy

Safety and Efficacy of Exenatide as Monotherapy in Drug Naive Patients With Type 2 Diabetes

This Phase 3 trial is designed to compare the effects of twice-daily exenatide and twice-daily placebo with respect to glycemic control in drug-naive patients with type 2 diabetes treated with diet and exercise.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: exenatide; Drug: exenatide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Aligarh, India
    • Research Site
  • Bangalore, India
    • Research Site
  • Chennai, India
    • Research Site
  • Indore, India
    • Research Site
  • Karnal, India
    • Research Site
  • New Delhi, India
    • Research Site
  • Vellore, India
    • Research Site
• Puerto Rico
  • Manati, Puerto Rico
    • Research Site
  • San Juan, Puerto Rico
    • Research Site
• Romania
  • Alba Iulia, Romania
    • Research Site
  • Baia Mare, Romania
    • Research Site
  • Bucuresti, Romania
    • Research Site
  • Galati, Romania
    • Research Site
  • Oradea, Romania
    • Research Site
  • Targu Mures, Romania
    • Research Site
• Russian Federation
  • Moscow, Russian Federation
    • Research Site
  • St. Petersburg, Russian Federation
    • Research Site
• United States
  • Idaho
    • Idaho Falls, Idaho, United States
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with type 2 diabetes
• Treating diabetes with diet and exercise
• HbA1c between 6.5% and 10.0%, inclusive
• Body Mass Index (BMI) between 25 kg/m^2 and 45 kg/m^2, inclusive

Exclusion Criteria:

• Have previously completed or withdrawn from this study
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
• Have been treated with any antidiabetic agent
• Have used drugs for weight loss (for example, Xenical, Meridia, Acutrim, or similar over-the counter medications) within 3 months of screening
• Are currently treated with any of the following excluded medications: * drugs that directly affect gastrointestinal motility; * systemic corticosteroids (excluding topical and inhaled preparations) by oral, intravenous, or intramuscular route used regularly (longer than 2 weeks) or used within 2 weeks immediately prior to screening for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide 5 mcg/exenatide 5 mcg; Exenatide 5 mcg; then exenatide 5 mcg	Drug: exenatide; Placebo subcutaneously injected twice daily as a lead-in followed by exenatide subcutaneously injected, 5 mcg, twice a day; Other Names: Byetta; Drug: exenatide; Placebo subcutaneously injected twice daily as a lead-in followed by exenatide subcutaneously injected, 5 mcg, twice a day, then exenatide subcutaneous injection, 10 mcg twice a day; Other Names: Byetta
Experimental: Exenatide 5 mcg/exenatide 10 mcg; Exenatide 5 mcg, then exenatide 10 mcg	Drug: exenatide; Placebo subcutaneously injected twice daily as a lead-in followed by exenatide subcutaneously injected, 5 mcg, twice a day; Other Names: Byetta; Drug: exenatide; Placebo subcutaneously injected twice daily as a lead-in followed by exenatide subcutaneously injected, 5 mcg, twice a day, then exenatide subcutaneous injection, 10 mcg twice a day; Other Names: Byetta
Placebo Comparator: Placebo; Placebo in volumes equivalent to exenatide	Drug: placebo; subcutaneous injection, volume equivalent to appropriate dose of exenatide, twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c (glycosylated hemoglobin) from Baseline to Week 24	Change in HbA1c from Baseline to Week 24	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects achieving HbA1c of 7% or less and of 6.5% or less	Percentage of subjects achieving HbA1c of 7% or less and of 6.5% or less	Baseline, Weeks 4, 8, 12, 16, 24
Change in fasting serum glucose (FSG) from Baseline to Week 24	Change in fasting serum glucose (FSG) from Baseline to Week 24 and, if measured, at all visits in between	Baseline, Weeks 4, 8, 12, 16, and 24
Change in body weight from Baseline to Week 24	Change in body weight (kg) from Baseline to Week 24 and, if measured, at all visits in between	Baseline, Weeks 4, 8, 12, 16, and 24
Change in glucose measurements from Baseline to Week 24	Change in fasting SMBG profiles (glucose measurements before and 2 hours after meals) from Baseline to Week 24 and, if measured, at all visits in between	Baseline, Weeks 4, 8, 12, 16, 24
Changes in beta-cell function and insulin sensitivity from Baseline to Week 24	Changes in beta-cell function and insulin sensitivity as assessed by homeostasis model assessment (HOMA) analyses from Baseline to Week 24 and, if measured, at all visits in between	Baseline, Weeks 4, 8, 12, 16, and 24
Changes in fasting and 30, 60, 120 and 180-minute glucose measurements	Changes in fasting and 30, 60, 120, 180-minute post glucose load blood concentrations of glucose and insulin	Immediately before glucose load, then 30, 60, 120, and 180 minutes post

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: James Malone, MD, Eli Lilly and Company

Publications and helpful links

General Publications

• Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.
• Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
• Moretto TJ, Milton DR, Ridge TD, Macconell LA, Okerson T, Wolka AM, Brodows RG. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2008 Aug;30(8):1448-60. doi: 10.1016/j.clinthera.2008.08.006. Erratum In: Clin Ther. 2008 Oct;30(10):1937.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: September 25, 2006
• First Submitted That Met QC Criteria: September 25, 2006
• First Posted (Estimate): September 27, 2006

Study Record Updates

• Last Update Posted (Estimate): February 23, 2015
• Last Update Submitted That Met QC Criteria: February 20, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: diabetes; monotherapy; exenatide; Lilly; Amylin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: H8O-MC-GWBJ