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

NCT00082381 | Completed Phase 3 Results

• 1 other identifier: H8O-MC-GWAA
• Study Type: interventional
• Target: 551
• Locations: 13 countries
• Sites: 91

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

Keywords

Diabetes; Insulin glargine; comparator; Amylin; Lilly

Outcome Measures

Primary Outcomes (1)

• Change in Glycosylated Hemoglobin (HbA1c)

  Change in HbA1c from baseline to week 26

  Baseline, week 26

Secondary Outcomes (6)

• Percentage of Patients Achieving HbA1c <=7%

  26 weeks

• Change in Body Weight

  Baseline, week 26

• Change in Fasting Serum Glucose

  Baseline, week 26

• Change in 7-point Self-monitored Blood Glucose (SMBG) Profile

  Baseline, week 26

• Percentage of Patients With Hypoglycemic Events

  26 weeks

Study Arms (2)

Exenatide Arm

EXPERIMENTAL

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

Drug: Exenatide (AC2993)

Insulin Glargine Arm

ACTIVE COMPARATOR

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

Drug: Insulin glargine

Interventions

Exenatide (AC2993) DRUG

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

Also known as: Byetta

Exenatide Arm

Insulin glargine DRUG

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

Also known as: Lantus

Insulin Glargine Arm

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (91)

Radiant Research-San Diego

San Diego, California, 92108, United States

Location

Dorothy L. and James E. Frank Diabetes Research Institute

San Mateo, California, 94401, United States

Location

Internal Medicine Associates Department of Research

Fort Myers, Florida, 33901, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Baptist Diabetes Associates

Miami, Florida, 33176, United States

Location

Metabolic Research Institute, Inc.

West Palm Beach, Florida, 33401, United States

Location

Springfield Diabetes & Endocrine Center

Springfield, Illinois, 62704, United States

Location

Frederick Primary Care Associates

Frederick, Maryland, 21702, United States

Location

Radiant Research, Inc.

St Louis, Missouri, 63141, United States

Location

Lovelace Scientific Resources, Inc.

Las Vegas, Nevada, 89102, United States

Location

Diabetes, Endocrine & Nutrition

Hampton, New Hampshire, 03842, United States

Location

Lovelace Scientific Resources

Albuquerque, New Mexico, 87108, United States

Location

Great Lakes Medical Research

Westfield, New York, 14787, United States

Location

DOCS, Beth Israel Medical Center

Yonkers, New York, 10710, United States

Location

Piedmont Medical Research Associates

Winston-Salem, North Carolina, 27103, United States

Location

Jon Shapiro, MD

Philadelphia, Pennsylvania, 19146, United States

Location

Endocrinology Consultants of East Tennessee

Knoxville, Tennessee, 37909, United States

Location

Israel Hartman, MD

Arlington, Texas, 76014, United States

Location

Diabetes & Glandular Research Associates, P.A.

San Antonio, Texas, 78229, United States

Location

Jack Wahlen, MD

Ogden, Utah, 84403, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98055, United States

Location

Australian Clinical Research Centre

Miranda, New South Wales, 2228, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Clinical Trial and Research Unit

Wollongong, New South Wales, 2500, Australia

Location

Royal Brisbane Hospital

Brisbane, Queensland, 4029, Australia

Location

Royal Adelaid Hospital

Adelaid, South Australia, 5000, Australia

Location

Repatriation General Hospital

Daw Park, South Australia, 5041, Australia

Location

SA Endocrine Clinical Research

Keswick, South Australia, 5035, Australia

Location

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, 3128, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Freemantle Hospital

Freemantle, Western Australia, Australia

Location

UZ Antwerpen

Endegem, 2650, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

A.Z. Jan Palfijn

Merksem, 2170, Belgium

Location

Sint Niklaasstraat

Sint-Gillis-Waas, 9170, Belgium

Location

Hospital Nossa Senhora das Gracas

Curitiba, PR 80810-990, Brazil

Location

Centro Integrado de Diabetes e Hipertensao

Fortaleza, CE 601200-020, Brazil

Location

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

Fortaleza, CE 60430-350, Brazil

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, RS 90020-090, Brazil

Location

Eiran Sairaala c/o9 Clires

Helsinki, Finland

Location

Torikeskuksen Laakariasema, Yliopistonkatu

Jyväskylä, Finland

Location

Oulu Deakoness Institution

Oulu, 90100, Finland

Location

Diabetologische Schwerpunktpraxis

Aschaffenburg, 63739, Germany

Location

Diabetologische Scherpunktpraxis

Bosenheim, 55545, Germany

Location

Diabetologische Schwerpunktpraxis

Dortmund, 44137, Germany

Location

Krankenhaus Bethanien

Hamburg, 20251, Germany

Location

Universitatskliniken des Saarlandes

Homburg/Saar, 66421, Germany

Location

IKFE GmbH

Mainz, Germany

Location

Profil Institut fur Stoffwechselforschung GmbH

Neuss, Germany

Location

Diabetologische Schwerpunktpraxis

Neuwied, 56564, Germany

Location

Diabetes Centrum Bilthoven

Bilthoven, 3723 MB, Netherlands

Location

Atrium Medisch Centrum Brunssum

Brunssum, 6422 BE, Netherlands

Location

Sint Antonius Ziekenhuis Nieuwegein

Nieuwegein, 3435 CM, Netherlands

Location

Refaja ziekenhuis

Stadskanaal, 9501 HE, Netherlands

Location

Medisch Centrum

Westeinde, Netherlands

Location

Markeveien Spesialistpraksis

Bergen, 5012, Norway

Location

Spesiallegetjenesten AS

Jessheim, 2050, Norway

Location

Betanien Spesialistsenter

Oslo, 0172, Norway

Location

Sykehuset Asker of Baerum HF

Rud, 1309, Norway

Location

Forskningsstiftelsen Hjertelaget

Stravanger, 4011, Norway

Location

Bydgoskie Centrum Diabetologii i Endokrynologii

Bydgoszcz, 85-822, Poland

Location

Oddzial Chorob Wewnetrznych

Częstochowa, 42-200, Poland

Location

NZOZ "Diab-Endo-Met"

Krakow, Poland

Location

Poradnia Diabetologiczna

Lodz, Rzgowska 281/289, Poland

Location

Poradnia Diabetologiczna

Lublin, 20-718, Poland

Location

Oddzial Chorob Wewnetrznych

Mielec, 39-300, Poland

Location

Oddzial Chorob Wewnetrznych i Diabetologii

Warsaw, 02-507, Poland

Location

Wojewodzka Poradnia dla Chorych na Cukrzyce

Warsaw, 03-242, Poland

Location

Hospital Garcia de Orta-Servico de Endocrinologia

Almada, 2805-267, Portugal

Location

Centro Hospitalar de Coimbra

Coimbra, 3040-853, Portugal

Location

Associacao Protectora dos Diabeticos de Portugal

Lisbon, 1250-203, Portugal

Location

Hospital Geral de Santo Antonio

Porto, 4099-001, Portugal

Location

Universidad Central del Caribe

Bayamón, 00956, Puerto Rico

Location

Hospital Alejandro Otero Lopez

Manatí, 00674, Puerto Rico

Location

Dr. Luis Ruiz

Ponce, 00733, Puerto Rico

Location

RCMI-Clinical Research Center

Rio Piedras, 00935, Puerto Rico

Location

San Juan Health Center

San Juan, 00936-3833, Puerto Rico

Location

Centro de Endocrinologia del Este

Yabucoa, 00767, Puerto Rico

Location

Hospital Vega Baja

Alicante, 03300, Spain

Location

Hospital Doce de Octubre

Madrid, 28041, Spain

Location

Hospital Gral de Mostoles

Madrid, 28934 Mostoles, Spain

Location

Hospital Virgen de Valme

Seville, 41014, Spain

Location

Hospital la Ribera, Alzira

Valencia, 46600 Alzira, Spain

Location

Lundberglaboratoriet for diabetesforskning

Gothenburg, 413 45, Sweden

Location

Medicinska kliniken

Helsingborg, 251 87, Sweden

Location

Kliniska Forskningsenheren

Lund, 221 85, Sweden

Location

Diabetesmottagningen, Intermedicinska kliniken

Stockholm, 118 83, Sweden

Location

CME, M71

Stockholm, 141 86, Sweden

Location

Enheten for metabol kontroll

Stockholm, 171 76, Sweden

Location

Related Publications (3)

• 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.

  PMID: 16230722 RESULT

• 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.

  PMID: 22913891 DERIVED

• 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.

  PMID: 22236356 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Exenatide; Insulin Glargine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Peter Ohman, Medical Science Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Chief Medical Officer, MD

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2004
• First Posted: May 11, 2004
• Study Start: June 1, 2003
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: April 7, 2015
• Results First Posted: July 31, 2013

Record last verified: 2015-03

Locations

NO (5); BE (6); PL (8); US (21); BR (4); PR (6); ES (5); SE (6); PT (4); FI (3); NL (5); AU (10); DE (8)