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

NCT ID: NCT00082381

Last Updated: 2015-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 551 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2008-07-31

Brief Summary

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).

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exenatide Arm

exenatide subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks

Group Type: EXPERIMENTAL

Exenatide (AC2993)

Intervention Type: DRUG

subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks

Insulin Glargine Arm

subcutaneous injection, once daily; forced titration to target blood glucose level

Group Type: ACTIVE_COMPARATOR

Insulin glargine

Intervention Type: DRUG

subcutaneous injection, once daily; forced titration to target blood glucose level

Interventions

Exenatide (AC2993)

subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks

Intervention Type: DRUG

Insulin glargine

subcutaneous injection, once daily; forced titration to target blood glucose level

Intervention Type: DRUG

Other Intervention Names

Byetta; Lantus

Eligibility 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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer, MD

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Radiant Research-San Diego

San Diego, California, United States

Dorothy L. and James E. Frank Diabetes Research Institute

San Mateo, California, United States

Internal Medicine Associates Department of Research

Fort Myers, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Baptist Diabetes Associates

Miami, Florida, United States

Metabolic Research Institute, Inc.

West Palm Beach, Florida, United States

Springfield Diabetes & Endocrine Center

Springfield, Illinois, United States

Frederick Primary Care Associates

Frederick, Maryland, United States

Radiant Research, Inc.

St Louis, Missouri, United States

Lovelace Scientific Resources, Inc.

Las Vegas, Nevada, United States

Diabetes, Endocrine & Nutrition

Hampton, New Hampshire, United States

Lovelace Scientific Resources

Albuquerque, New Mexico, United States

Great Lakes Medical Research

Westfield, New York, United States

DOCS, Beth Israel Medical Center

Yonkers, New York, United States

Piedmont Medical Research Associates

Winston-Salem, North Carolina, United States

Jon Shapiro, MD

Philadelphia, Pennsylvania, United States

Endocrinology Consultants of East Tennessee

Knoxville, Tennessee, United States

Israel Hartman, MD

Arlington, Texas, United States

Diabetes & Glandular Research Associates, P.A.

San Antonio, Texas, United States

Jack Wahlen, MD

Ogden, Utah, United States

Rainier Clinical Research Center, Inc.

Renton, Washington, United States

Australian Clinical Research Centre

Miranda, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Clinical Trial and Research Unit

Wollongong, New South Wales, Australia

Royal Brisbane Hospital

Brisbane, Queensland, Australia

Royal Adelaid Hospital

Adelaid, South Australia, Australia

Repatriation General Hospital

Daw Park, South Australia, Australia

SA Endocrine Clinical Research

Keswick, South Australia, Australia

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Freemantle Hospital

Freemantle, Western Australia, Australia

UZ Antwerpen

Endegem, , Belgium

UZ Gent

Ghent, , Belgium

UZ Gasthuisberg

Leuven, , Belgium

CHU Sart Tilman

Liège, , Belgium

A.Z. Jan Palfijn

Merksem, , Belgium

Sint Niklaasstraat

Sint-Gillis-Waas, , Belgium

Hospital Nossa Senhora das Gracas

Curitiba, , Brazil

Centro Integrado de Diabetes e Hipertensao

Fortaleza, , Brazil

Centro de Pesquisas em Diabetes e Doencas Endocrino Metabolicas/HUWC/UFC

Fortaleza, , Brazil

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Eiran Sairaala c/o9 Clires

Helsinki, , Finland

Torikeskuksen Laakariasema, Yliopistonkatu

Jyväskylä, , Finland

Oulu Deakoness Institution

Oulu, , Finland

Diabetologische Schwerpunktpraxis

Aschaffenburg, , Germany

Diabetologische Scherpunktpraxis

Bosenheim, , Germany

Diabetologische Schwerpunktpraxis

Dortmund, , Germany

Krankenhaus Bethanien

Hamburg, , Germany

Universitatskliniken des Saarlandes

Homburg/Saar, , Germany

IKFE GmbH

Mainz, , Germany

Profil Institut fur Stoffwechselforschung GmbH

Neuss, , Germany

Diabetologische Schwerpunktpraxis

Neuwied, , Germany

Diabetes Centrum Bilthoven

Bilthoven, , Netherlands

Atrium Medisch Centrum Brunssum

Brunssum, , Netherlands

Sint Antonius Ziekenhuis Nieuwegein

Nieuwegein, , Netherlands

Refaja ziekenhuis

Stadskanaal, , Netherlands

Medisch Centrum

Westeinde, , Netherlands

Markeveien Spesialistpraksis

Bergen, , Norway

Spesiallegetjenesten AS

Jessheim, , Norway

Betanien Spesialistsenter

Oslo, , Norway

Sykehuset Asker of Baerum HF

Rud, , Norway

Forskningsstiftelsen Hjertelaget

Stravanger, , Norway

Bydgoskie Centrum Diabetologii i Endokrynologii

Bydgoszcz, , Poland

Oddzial Chorob Wewnetrznych

Częstochowa, , Poland

NZOZ "Diab-Endo-Met"

Krakow, , Poland

Poradnia Diabetologiczna

Lodz, , Poland

Poradnia Diabetologiczna

Lublin, , Poland

Oddzial Chorob Wewnetrznych

Mielec, , Poland

Oddzial Chorob Wewnetrznych i Diabetologii

Warsaw, , Poland

Wojewodzka Poradnia dla Chorych na Cukrzyce

Warsaw, , Poland

Hospital Garcia de Orta-Servico de Endocrinologia

Almada, , Portugal

Centro Hospitalar de Coimbra

Coimbra, , Portugal

Associacao Protectora dos Diabeticos de Portugal

Lisbon, , Portugal

Hospital Geral de Santo Antonio

Porto, , Portugal

Universidad Central del Caribe

Bayamón, , Puerto Rico

Hospital Alejandro Otero Lopez

Manatí, , Puerto Rico

Dr. Luis Ruiz

Ponce, , Puerto Rico

RCMI-Clinical Research Center

Rio Piedras, , Puerto Rico

San Juan Health Center

San Juan, , Puerto Rico

Centro de Endocrinologia del Este

Yabucoa, , Puerto Rico

Hospital Vega Baja

Alicante, , Spain

Hospital Doce de Octubre

Madrid, , Spain

Hospital Gral de Mostoles

Madrid, , Spain

Hospital Virgen de Valme

Seville, , Spain

Hospital la Ribera, Alzira

Valencia, , Spain

Lundberglaboratoriet for diabetesforskning

Gothenburg, , Sweden

Medicinska kliniken

Helsingborg, , Sweden

Kliniska Forskningsenheren

Lund, , Sweden

Diabetesmottagningen, Intermedicinska kliniken

Stockholm, , Sweden

CME, M71

Stockholm, , Sweden

Enheten for metabol kontroll

Stockholm, , Sweden

Countries

United States; Australia; Belgium; Brazil; Finland; Germany; Netherlands; Norway; Poland; Portugal; Puerto Rico; Spain; Sweden

References

Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG; GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005 Oct 18;143(8):559-69. doi: 10.7326/0003-4819-143-8-200510180-00006.

Reference Type: RESULT

PMID: 16230722 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22913891 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22236356 (View on PubMed)

Other Identifiers

H8O-MC-GWAA

Identifier Type: -

Identifier Source: org_study_id