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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00082381
First received: May 6, 2004
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Exenatide (AC2993)
Drug: Insulin glargine
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: Effect of AC2993 (Synthetic Exendin-4) Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to week 26


Secondary Outcome Measures:
  • Percentage of Patients Achieving HbA1c <=7% [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    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%).

  • Change in Body Weight [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    Change in body weight from baseline to week 26

  • Change in Fasting Serum Glucose [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    Change in fasting serum glucose from baseline to week 26

  • Change in 7-point Self-monitored Blood Glucose (SMBG) Profile [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    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

  • Percentage of Patients With Hypoglycemic Events [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    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

  • Change in Rate of Hypoglycemic Events [ Time Frame: Baseline, week 26 ] [ Designated as safety issue: No ]
    Change in rate of hypoglycemic events per 30 days per patient from baseline to week 26


Enrollment: 551
Study Start Date: June 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
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 Name: 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 Name: Lantus

  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 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.
  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: NCT00082381

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00082381     History of Changes
Other Study ID Numbers: H8O-MC-GWAA
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

Keywords provided by AstraZeneca:
Diabetes
Insulin glargine
comparator
Amylin
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Glargine
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014