Evaluation of the Effect on Glucose Control of AC2993 in Patients With Type 2 Diabetes Mellitus

A Phase 3, Randomized, Triple-Blind, Parallel-Group, Long-Term, Placebo-Controlled, Multicenter Study to Examine the Effect on Glucose Control (HbA1c) of AC2993 Given Twice Daily in Subjects With Type 2 Diabetes Mellitus Treated With Metformin and a Sulfonylurea

This is a multicenter, randomized, blinded, placebo-controlled study to assess the effects on glucose control of AC2993 as compared to placebo in patients with type 2 diabetes. Patients will be randomized into one of two AC2993 treatment arms or to placebo treatment and will continue with their required existing diabetes medications (metformin and a sulfonylurea) throughout the study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Non-Insulin-Dependent
• Intervention / Treatment: Drug: AC2993; Drug: Placebo; Drug: AC2993; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 734
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
    • Birmingham, Alabama, United States, 35206
      • Parkway Medical Center
    • Montgomery, Alabama, United States, 36106
      • Extended Arm Physicians/ Southern Drug
    • Tallassee, Alabama, United States, 36078
      • Southern Drug Research Network
  • Arkansas
    • Fayetteville, Arkansas, United States, 72701
      • First Care Family Doctors
    • Little Rock, Arkansas, United States, 72205
      • Physicians Group Research Clinic, LLC
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Concord, California, United States
      • East Bay Clinical Trial Center
    • Encino, California, United States, 91436
      • Medical Group of Encino
    • Fresno, California, United States, 93720
      • Valley Research
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Healthcare
    • La Jolla, California, United States, 92037
      • Whittier Institute for Diabetes
    • Los Gatos, California, United States, 95032
      • Richard Cherlin, M.D.
    • Moreno Valley, California, United States, 92553
      • Dr. Martinez Medical Clinic
    • Redwood City, California, United States, 94062
      • Comprehensive Diabetes-Endocrine Medical Associates
    • San Diego, California, United States, 92108
      • Radiant Research-San Diego
    • San Diego, California, United States, 92161
      • Veterans Medical Research Foundation
    • Walnut Creek, California, United States
      • Diablo Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80209
      • Creekside Endocrine Associates
    • Denver, Colorado, United States, 80262
      • University of Colorado-Barbara Davis Center for Childhood Diabetes
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
    • Washington, District of Columbia, United States, 20003-4393
      • MedStar Clinical Research
  • Florida
    • Aventura, Florida, United States
      • Medical Research Unlimited
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • Clearwater, Florida, United States, 33756
      • Morton Plant Mease Health Care
    • Ft. Myers, Florida, United States
      • Internal Medicine Associates
    • Gainesville, Florida, United States, 32605
      • Clin Sci International
    • Jacksonville, Florida, United States, 32204
      • Northeast Florida Endocrine & Diabetes Research
    • Jupiter, Florida, United States, 33458
      • Jupiter Research Institute
    • Miami, Florida, United States, 33176
      • Baptist Diabetes Associates
    • Sarasota, Florida, United States, 34232
      • Comprehensive NeuroScience Inc.
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Endocrine Associates
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Georgia
    • Columbus, Georgia, United States, 31901
      • Columbus Metabolic Foundation
  • Hawaii
    • Ewa Beach, Hawaii, United States, 96706
      • University of Hawaii-Diabetes Research Group
  • Illinois
    • Belvidere, Illinois, United States, 61008
      • University Primary Care Center at Belvidere
    • Chicago, Illinois, United States, 60612
      • Cook County Hospital
    • Chicago, Illinois, United States, 60602
      • Northwestern Memorial Physicians Group
    • Chicago, Illinois, United States, 60610
      • Illinois Center for Clinical Trials
  • Indiana
    • Indianapolis, Indiana, United States, 46222
      • American Health Network
    • Indianapolis, Indiana, United States
      • Indiana University Outpatient Clinical Research
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Lipid, Atherosclerosis & Metabolic Clinic
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates
    • Lexington, Kentucky, United States, 40503
      • Kentucky Diabetes Center
    • Lexington, Kentucky, United States, 40536-9841
      • University of Kentucky Metabolic Research Group
    • Louisville, Kentucky, United States, 40223
      • MedResearch, Inc.
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21012
      • University of Maryland-Joslin Diabetes Center
  • Massachusetts
    • Waltham, Massachusetts, United States, 02154
      • Clinica Research Inc.
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States
      • Grand Rapids Associated Interns
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • International Diabetes Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Diabetes and Endocrinology Specialists
    • Excelsior Springs, Missouri, United States, 64024
      • Medical Arts Research Collaborative
    • Kansas City, Missouri, United States, 64111
      • St Lukes Lipid and Diabetes Research Center
    • Rolla, Missouri, United States, 65401
      • Mid Missouri Research Specialists, Inc.
    • St. Louis, Missouri, United States, 63141
      • Radiant Research-St. Louis
    • St. Peters, Missouri, United States, 63376
      • Midwest Pharmaceutical Research
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Lovelace Scientific Resources-Las Vegas
    • Reno, Nevada, United States, 89502
      • Lisa Abbott, MD
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate
    • New York, New York, United States, 10025
      • St. Lukes Roosevelt Hospital
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
    • Yonkers, New York, United States, 10710
      • DOCS at Beth Israel Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Charlotte Clinical Research
    • Durham, North Carolina, United States, 27713
      • UNC Diabetes Care Center
    • Hickory, North Carolina, United States, 28601
      • Unifour Medical Research
    • Wilmington, North Carolina, United States, 28412
      • New Hanover Medical Research Associates
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Radiant Research-Columbus
    • Mentor, Ohio, United States, 44060
      • University Mednet
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Sciences Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Medford Medical Clinic
    • Portland, Oregon, United States
      • Radiant Research
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States
      • Physicians for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Diabetes Research Center
    • Philadelphia, Pennsylvania, United States, 19146
      • Philadelphia Health Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Chester, South Carolina, United States, 29706
      • CNS Clinical Trials
    • Mt. Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Memphis, Tennessee, United States, 38119
      • The Endocrine Clinic
    • Nashville, Tennessee, United States, 37203
      • Mid State Endocrine Associates
  • Texas
    • Arlington, Texas, United States, 76014
      • Israel A. Hartman, M.D.
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrinology Research Center
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences-Internal Medicine
    • Irving, Texas, United States, 75038
      • North Texas Clinical Research
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Sciences Center-Texas Diabetes Institute
    • San Antonio, Texas, United States, 78229-3894
      • Diabetes and Glandular Disease Clinic
    • San Antonio, Texas, United States, 78229
      • SAM Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Salt Lake Research
    • Salt Lake City, Utah, United States, 84108
      • Utah Diabetes Center at the University of Utah
  • Virginia
    • Arlington, Virginia, United States, 22204
      • Medical Associates of Northern Virginia
  • Washington
    • Olympia, Washington, United States, 98502
      • West Olympia Internal Medicine
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic
  • Wisconsin
    • Madison, Wisconsin, United States, 53711
      • University of Wisconsin West Clinic
    • Milwaukee, Wisconsin, United States, 53215
      • Midwest Endocrinology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with Type 2 diabetes mellitus
• Treated with both metformin and a sulfonylurea at defined doses for at least 3 months prior to screening
• BMI= 27-45 kg/m2
• HbA1c value between 7.5% and 11%

Exclusion Criteria:

• Treated with oral anti-diabetic medications other than metformin and sulfonylurea within 3 months of screening
• Patients treated previously with AC2993
• Patients presently treated with insulin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC2993 5 mcg (0.02 mL); Placebo, then AC2993 5 mcg, then AC2993 5 mcg	Drug: AC2993; Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily; Other Names: synthetic exendin-4; Drug: AC2993; Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5 mcg (0.02 mL) for 4 weeks / AC2993 10 mcg (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily; Other Names: synthetic exendin-4
Experimental: AC2993 10mcg (0.04 mL); Placebo, then AC2993 5 mcg, then AC2993 10 mcg	Drug: AC2993; Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily; Other Names: synthetic exendin-4; Drug: AC2993; Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5 mcg (0.02 mL) for 4 weeks / AC2993 10 mcg (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily; Other Names: synthetic exendin-4
Placebo Comparator: Placebo 0.02 mL; Placebo 0.02 mL, then Placebo 0.02 mL, then Placebo 0.02 mL	Drug: Placebo; Placebo Lead In (0.02 mL) for 4 weeks / Placebo mcg (0.02 mL) for 4 weeks / Placebo (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily; Drug: Placebo; Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily
Placebo Comparator: Placebo 0.04 mL; Placebo 0.02 mL, then Placebo 0.02 mL, then Placebo 0.04 mL	Drug: Placebo; Placebo Lead In (0.02 mL) for 4 weeks / Placebo mcg (0.02 mL) for 4 weeks / Placebo (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily; Drug: Placebo; Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c from Baseline to Week 30	Change in HbA1c from Baseline (Day 1) to study termination (Week 30)	Baseline (Day 1) to Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of subjects achieving HbA1c target values of < 7% and < 8% by Week 30	The number of subjects achieving HbA1c target values of < 7% and < 8% by study termination (Week 30)	Baseline (Day 1) and Week 30
The number of subjects achieving HbA1c reductions of > 0.5% and > 1.0% by Week 30	The number of subjects achieving HbA1c reductions of > 0.5% and > 1.0% by study termination (Week 30)	Baseline (Day 1), and Week 30
The time to achieve HbA1c reductions of 0.5% or more and >1.0% or more	The time it takes subjects to achieve HbA1c reductions of 0.5% or more and >1.0% or more	Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24, Week 30
The time to achieve specific HbA1c target values of < 7% and < 8%	The time it takes subjects to achieve HbA1c target values of < 7% and < 8%	Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24, Week 30
Change in body weight from Baseline to each intermediate visit and Week 30	Change in body weight (kg) from Baseline to each intermediate visit and Week 30	Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, Week 24, Week 30
Change in HbA1c from baseline (Day 1) to each of the intermediate visits	Change in HbA1c from baseline, measured from Visit 3 (Day 1) to each of the intermediate visits (Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, and Week 24)	Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca

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.
• Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005 May;28(5):1083-91. doi: 10.2337/diacare.28.5.1083.

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): August 1, 2003
• Study Completion (Actual): August 1, 2003

Study Registration Dates

• First Submitted: May 7, 2002
• First Submitted That Met QC Criteria: May 7, 2002
• First Posted (Estimate): May 8, 2002

Study Record Updates

• Last Update Posted (Estimate): February 24, 2015
• Last Update Submitted That Met QC Criteria: February 23, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitis
• 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: 2993-115