Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

NCT ID: NCT00082407

Last Updated: 2015-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 505 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30
• Study Completion Date: 2008-07-31

Brief Summary

This is a Phase 3, multicenter, open-label, comparator-controlled trial comparing the effect of exenatide twice daily to twice daily biphasic insulin aspart 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

subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks

Group Type: EXPERIMENTAL

exenatide

Intervention Type: DRUG

subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks

Biphasic Insulin Aspart Arm

subcutaneous injection, twice daily; titration to target blood glucose level

Group Type: ACTIVE_COMPARATOR

biphasic insulin aspart

Intervention Type: DRUG

subcutaneous injection, twice daily; titration to target blood glucose level

Interventions

exenatide

subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks

Intervention Type: DRUG

biphasic insulin aspart

subcutaneous injection, twice daily; titration to target blood glucose level

Intervention Type: DRUG

Other Intervention Names

Byetta; NovoLog

Eligibility Criteria

Inclusion Criteria

• Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 1. >=1500 mg/day immediate-release metformin or extended-release metformin and at least an optimally effective dose for brand of 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 11.0%, inclusive.
• Patients have a body mass index >25kg/m2 and <40 kg/m2.
• Female patients are not breastfeeding, and female patients of childbearing potential test negative for pregnancy, do not intend to become pregnant during the study, and agree to continue using a reliable method of birth control

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 previously, in this or any other study, received exenatide or glucagon-like peptide-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 have less than 5 years of remission history from any malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate 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 biphasic insulin aspart, exenatide, or excipients contained in these agents.
• Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label.
• Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.2 mg/dL for females.
• Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase greater than three times the upper limit of the reference range.
• Patients have known hemoglobinopathy or chronic anemia.
• Patients have active proliferative retinopathy or macular edema.
• Patients are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
• 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 been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides.
• 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

Clinical Hospital Osijek

Osijek, , Croatia

Klinica bolnica Dubrava

Zagreb, , Croatia

Klinicki bolnicki centar Zagreb-Rebro

Zagreb, , Croatia

Opca bolnica "Sveti Duh"

Zagreb, , Croatia

Internistische Gemeinschaftspraxis

Augsburg, , Germany

Dr. Karlheinz Hehemann

Beckum, , Germany

Dr. Klaus Busch

Dortmund, , Germany

Medical Clinic and Policlinic 3

Giessen, , Germany

Diabetologische Schwerpunktpraxis

Hamburg, , Germany

IKFE GmbH

Mainz, , Germany

Institut for diabetic research

Munich, , Germany

Profil, Institut fur Stoffwechselstorungen

Neuss, , Germany

Dr. Thomas Behnke

Neuwied, , Germany

Dr. Bernd Donaubauer

Oschatz, , Germany

Marienhospital Osnabruck

Osnabrück, , Germany

Dr. Joerg Steindorf

Schkeuditz, , Germany

Dr. Jerzi Jasinski

Wiesbaden, , Germany

"Polyclinic" General Hospital of Athens

Athens, , Greece

Department of Endocrinology

Athens, , Greece

Diabetes Center

Athens, , Greece

University Hospital of Patras

Pátrai, , Greece

1st Internal Medicine Department "Papagergiou"

Thessaloniki, , Greece

Instituto di Endocrinologia

Catania, , Italy

Dipartimento di fisiopatologia clinica

Florence, , Italy

U.O. Medicina Generale

Milan, , Italy

Ospedale Civile di Padova

Padua, , Italy

Policlinico Univarsitario P. Giaccone

Palermo, , Italy

U.O. Universita di Malattie del Metabolismo e Diabetologia

Torino, , Italy

Gelre Ziekenhuizen

Apeldoorn, , Netherlands

Rijnstate Ziekenhuis

Arnhem, , Netherlands

Maxima Medisch Centrum Location Eindhoven

Eindhoven, , Netherlands

Hospitais da Universidade de Coimbra

Coimbra, , Portugal

Hospital de Santo Andre

Leiria, , Portugal

Associacao Protectora dos Diabeticos de Portugal

Lisbon, , Portugal

Hospital Pedro Hispano

Matosinhos Municipality, , Portugal

Spitalul Judetean Brasov

Brasov, , Romania

Institutul de Diabet

Bucharest, , Romania

Spitalul Clinic nr. 1 Judetean

Judet Timis, , Romania

National Endocrinology Research Center

Moscow, , Russia

Setchenov Moscow Medical Academy

Moscow, , Russia

Moscow State Medical Stomatological

Moscow, , Russia

Russian Medical Academy for Advanced Medical Studies, Ministry of Health

Moscow, , Russia

Hospital of St. Elizabeth's

Saint Petersburg, , Russia

City Clinical Hospital #2

Saint Petersburg, , Russia

Medical Military Academy

Saint Petersburg, , Russia

Univerzitetni klinicni center Ljubljana

Ljubljana, , Slovenia

Splosna bolnisnica Maribor

Maribor, , Slovenia

Hospital Vega Baja

Alicante, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Endocrinology Service (Planta Baja)

Palma de Mallorca, , Spain

Hospital Virgen de Valme

Seville, , Spain

Hospital General de Teruel

Teruel, , Spain

Hospital la Ribera Alzira

Valencia, , Spain

Changhua Christian Hospital

Changhua, , Taiwan

Tzu Chi General Hospital

Hualien City, , Taiwan

Veteran General Hospital-Taichung

Taichung, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Diabetes Research, Ward 34, Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Diabetes Unit, Blackburn Royal Infirmary

Blackburn, , United Kingdom

Colchester General Hospital

Colchester, , United Kingdom

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Glasgow Royal Infirmary

Glasgow, , United Kingdom

The Michael White Center for Diabetes and Endocrinology

Hull, , United Kingdom

Clinical Sciences Centre

Liverpool, , United Kingdom

Education Centre, James Cook University Hospital

Middlesbrough, , United Kingdom

Wellcome Labs, Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Queens Medical Centre

Nottingham, , United Kingdom

Diabetes Trial Unit OCDEM, Churchill Hospital

Oxford, , United Kingdom

Diabetes Unit, Gladsone Centre, Maelor Hospital

Wrexham, , United Kingdom

Countries

Croatia; Germany; Greece; Italy; Netherlands; Portugal; Romania; Russia; Slovenia; Spain; Taiwan; United Kingdom

References

Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia. 2007 Feb;50(2):259-67. doi: 10.1007/s00125-006-0510-2. Epub 2006 Dec 8.

Reference Type: RESULT

PMID: 17160407 (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-GWAD

Identifier Type: -

Identifier Source: org_study_id