Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

March 19, 2015 updated by: AstraZeneca

Effect of AC2993 (Synthetic Exendin-4) Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

This is a multicenter, comparator-controlled, open-label, randomized, two-arm, parallel trial to compare the effect of exenatide twice daily and insulin glargine on glycemic control, as measured by hemoglobin A1c (HbA1c).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

551

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Miranda, New South Wales, Australia, 2228
        • Australian Clinical Research Centre
      • St. Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
      • Wollongong, New South Wales, Australia, 2500
        • Clinical Trial and Research Unit
    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Royal Brisbane Hospital
    • South Australia
      • Adelaid, South Australia, Australia, 5000
        • Royal Adelaid Hospital
      • Daw Park, South Australia, Australia, 5041
        • Repatriation General Hospital
      • Keswick, South Australia, Australia, 5035
        • SA Endocrine Clinical Research
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Eastern Health (Box Hill Hospital)
      • Parkville, Victoria, Australia, 3050
        • Royal Melbourne Hospital
    • Western Australia
      • Freemantle, Western Australia, Australia
        • Freemantle Hospital
  • Belgium
      • Endegem, Belgium, 2650
        • UZ Antwerpen
      • Gent, Belgium, 9000
        • Uz Gent
      • Leuven, Belgium, 3000
        • Uz Gasthuisberg
      • Liege, Belgium, 4000
        • CHU Sart Tilman
      • Merksem, Belgium, 2170
        • A.Z. Jan Palfijn
      • Sint Gillis Waas, Belgium, 9170
        • Sint Niklaasstraat
  • Brazil
      • Curitiba, Brazil, PR 80810-990
        • Hospital Nossa Senhora Das Gracas
      • Fortaleza, Brazil, CE 601200-020
        • Centro Integrado de Diabetes e Hipertensao
      • Fortaleza, Brazil, CE 60430-350
        • Centro de Pesquisas em Diabetes e Doencas Endocrino Metabolicas/HUWC/UFC
      • Porto Alegre, Brazil, RS 90020-090
        • Santa Casa de Misericordia de Porto Alegre
  • Finland
      • Helsinki, Finland
        • Eiran Sairaala c/o9 Clires
      • Jyvaskyla, Finland
        • Torikeskuksen Laakariasema, Yliopistonkatu
      • Oulu, Finland, 90100
        • Oulu Deakoness Institution
  • Germany
      • Aschaffenburg, Germany, 63739
        • Diabetologische Schwerpunktpraxis
      • Bosenheim, Germany, 55545
        • Diabetologische Scherpunktpraxis
      • Dortmund, Germany, 44137
        • Diabetologische Schwerpunktpraxis
      • Hamburg, Germany, 20251
        • Krankenhaus Bethanien
      • Homburg/Saar, Germany, 66421
        • Universitätskliniken des Saarlandes
      • Mainz, Germany
        • IKFE GmbH
      • Neuss, Germany
        • Profil Institut für Stoffwechselforschung GmbH
      • Neuwied, Germany, 56564
        • Diabetologische Schwerpunktpraxis
  • Netherlands
      • Bilthoven, Netherlands, 3723 MB
        • Diabetes Centrum Bilthoven
      • Brunssum, Netherlands, 6422 BE
        • Atrium Medisch Centrum Brunssum
      • Nieuwegein, Netherlands, 3435 CM
        • Sint Antonius Ziekenhuis Nieuwegein
      • Stadskanaal, Netherlands, 9501 HE
        • Refaja ziekenhuis
      • Westeinde, Netherlands
        • Medisch Centrum
  • Norway
      • Bergen, Norway, 5012
        • Markeveien Spesialistpraksis
      • Jessheim, Norway, 2050
        • Spesiallegetjenesten AS
      • Oslo, Norway, 0172
        • Betanien Spesialistsenter
      • Rud, Norway, 1309
        • Sykehuset Asker of Baerum HF
      • Stravanger, Norway, 4011
        • Forskningsstiftelsen Hjertelaget
  • Poland
      • Bydgoszcz, Poland, 85-822
        • Bydgoskie Centrum Diabetologii i Endokrynologii
      • Czestochowa, Poland, 42-200
        • Oddzial Chorob Wewnetrznych
      • Krakow, Poland
        • NZOZ "Diab-Endo-Met"
      • Lodz, Poland, Rzgowska 281/289
        • Poradnia Diabetologiczna
      • Lublin, Poland, 20-718
        • Poradnia Diabetologiczna
      • Mielec, Poland, 39-300
        • Oddzial Chorob Wewnetrznych
      • Warszawa, Poland, 02-507
        • Oddzial Chorob Wewnetrznych i Diabetologii
      • Warszawa, Poland, 03-242
        • Wojewodzka Poradnia dla Chorych na Cukrzyce
  • Portugal
      • Almada, Portugal, 2805-267
        • Hospital Garcia de Orta-Servico de Endocrinologia
      • Coimbra, Portugal, 3040-853
        • Centro Hospitalar de Coimbra
      • Lisboa, Portugal, 1250-203
        • Associação Protectora dos Diabéticos de Portugal
      • Porto, Portugal, 4099-001
        • Hospital Geral de Santo Antonio
  • Puerto Rico
      • Bayamon, Puerto Rico, 00956
        • Universidad Central del Caribe
      • Manati, Puerto Rico, 00674
        • Hospital Alejandro Otero Lopez
      • Ponce, Puerto Rico, 00733
        • Dr. Luis Ruiz
      • Rio Piedras, Puerto Rico, 00935
        • RCMI-Clinical Research Center
      • San Juan, Puerto Rico, 00936-3833
        • San Juan Health Center
      • Yabucoa, Puerto Rico, 00767
        • Centro de Endocrinologia del Este
  • Spain
      • Alicante, Spain, 03300
        • Hospital Vega Baja
      • Madrid, Spain, 28041
        • Hospital Doce de Octubre
      • Madrid, Spain, 28934 Mostoles
        • Hospital Gral de Mostoles
      • Sevilla, Spain, 41014
        • Hospital Virgen de Valme
      • Valencia, Spain, 46600 Alzira
        • Hospital la Ribera, Alzira
  • Sweden
      • Goteborg, Sweden, 413 45
        • Lundberglaboratoriet for diabetesforskning
      • Helsingborg, Sweden, 251 87
        • Medicinska kliniken
      • Lund, Sweden, 221 85
        • Kliniska Forskningsenheren
      • Stockholm, Sweden, 118 83
        • Diabetesmottagningen, Intermedicinska kliniken
      • Stockholm, Sweden, 141 86
        • CME, M71
      • Stockholm, Sweden, 171 76
        • Enheten for metabol kontroll
  • United States
    • California
      • San Diego, California, United States, 92108
        • Radiant Research-San Diego
      • San Mateo, California, United States, 94401
        • Dorothy L. and James E. Frank Diabetes Research Institute
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Internal Medicine Associates Department of Research
      • Jacksonville, Florida, United States, 32216
        • Jacksonville Center for Clinical Research
      • Miami, Florida, United States, 33176
        • Baptist Diabetes Associates
      • West Palm Beach, Florida, United States, 33401
        • Metabolic Research Institute, Inc.
    • Illinois
      • Springfield, Illinois, United States, 62704
        • Springfield Diabetes & Endocrine Center
    • Maryland
      • Frederick, Maryland, United States, 21702
        • Frederick Primary Care Associates
    • Missouri
      • St. Louis, Missouri, United States, 63141
        • Radiant Research, Inc.
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Lovelace Scientific Resources, Inc.
    • New Hampshire
      • Hampton, New Hampshire, United States, 03842
        • Diabetes, Endocrine & Nutrition
    • New Mexico
      • Albuquerque, New Mexico, United States, 87108
        • Lovelace Scientific Resources
    • New York
      • Westfield, New York, United States, 14787
        • Great Lakes Medical Research
      • Yonkers, New York, United States, 10710
        • DOCS, Beth Israel Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Piedmont Medical Research Associates
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19146
        • Jon Shapiro, MD
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Endocrinology Consultants of East Tennessee
    • Texas
      • Arlington, Texas, United States, 76014
        • Israel Hartman, MD
      • San Antonio, Texas, United States, 78229
        • Diabetes & Glandular Research Associates, P.A.
    • Utah
      • Ogden, Utah, United States, 84403
        • Jack Wahlen, MD
    • Washington
      • Renton, Washington, United States, 98055
        • Rainier Clinical Research Center, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients have been treated with a stable dose of one of the following for at least 3 months prior to screening: 1. 1500 to 2550 mg/day immediate-release metformin (or 1500 to 2000 mg/day extended-release metformin) and at least an optimally effective dose of a 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 10.0%, inclusive.
  • History of stable body weight (not varying by >10% for at least three months prior to screening).
  • Female patients are not breastfeeding, and female patients of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause)

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 participated in this study previously or any other study using AC2993 or GLP-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 are undergoing therapy for a malignancy, other than basal cell or squamous cell skin 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 insulin glargine, AC2993, or excipients contained in these agents.
  • Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label, in the opinion of the investigator.
  • Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.3 mg/dL for females.
  • Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamicpyruvic transaminase greater than three times the upper limit of the reference range.
  • Patients have known hemoglobinopathy or chronic anemia.
  • 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exenatide Arm
exenatide subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks
Drug: Exenatide (AC2993)
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks
Other Names:
  • Byetta
Active Comparator: Insulin Glargine Arm
subcutaneous injection, once daily; forced titration to target blood glucose level
Drug: Insulin glargine
subcutaneous injection, once daily; forced titration to target blood glucose level
Other Names:
  • Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Glycosylated Hemoglobin (HbA1c)
Time Frame: Baseline, week 26
Change in HbA1c from baseline to week 26
Baseline, week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients Achieving HbA1c <=7%
Time Frame: 26 weeks
Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 26 (percentage = [number of subjects with HbA1c <=7% at week 26 divided by number of subjects with HbA1c >7% at baseline] * 100%).
26 weeks
Change in Body Weight
Time Frame: Baseline, week 26
Change in body weight from baseline to week 26
Baseline, week 26
Change in Fasting Serum Glucose
Time Frame: Baseline, week 26
Change in fasting serum glucose from baseline to week 26
Baseline, week 26
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Time Frame: Baseline, week 26
Change in 7-point (pre-breakfast, 2 hour post breakfast, pre-lunch, 2 hour post lunch, pre-dinner, 2 hour post dinner, 0300 hours) SMBG profile from baseline to week 26
Baseline, week 26
Percentage of Patients With Hypoglycemic Events
Time Frame: 26 weeks
Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study divided by the total number of patients who participated in the 26 week Parent Study
26 weeks
Change in Rate of Hypoglycemic Events
Time Frame: Baseline, week 26
Change in rate of hypoglycemic events per 30 days per patient from baseline to week 26
Baseline, week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2003

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

July 1, 2008

Study Registration Dates

First Submitted

May 6, 2004

First Submitted That Met QC Criteria

May 10, 2004

First Posted (Estimate)

May 11, 2004

Study Record Updates

Last Update Posted (Estimate)

April 7, 2015

Last Update Submitted That Met QC Criteria

March 19, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H8O-MC-GWAA

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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