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

NCT00082407 | Completed Phase 3 Results

• 1 other identifier: H8O-MC-GWAD
• Study Type: interventional
• Target: 505
• Locations: 12 countries
• Sites: 69

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

Keywords

diabetes; exendin; Amylin; Lilly; insulin aspart

Outcome Measures

Primary Outcomes (1)

• Change in Glcosylated Hemoglobin (HbA1c)

  Change in HbA1c from baseline to week 52

  baseline, week 52

Secondary Outcomes (6)

• Percentage of Patients Achieving HbA1c <=7%

  52 weeks

• Change in Body Weight

  baseline, week 52

• Change in Fasting Serum Glucose

  baseline, week 52

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

  baseline, week 52

• Percentage of Patients With Hypoglycemic Events

  52 weeks

Study Arms (2)

Exenatide Arm

EXPERIMENTAL

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

Drug: exenatide

Biphasic Insulin Aspart Arm

ACTIVE COMPARATOR

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

Drug: biphasic insulin aspart

Interventions

exenatide DRUG

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

Also known as: Byetta

Exenatide Arm

biphasic insulin aspart DRUG

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

Also known as: NovoLog

Biphasic Insulin Aspart 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 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

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 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (69)

Clinical Hospital Osijek

Osijek, 31000, Croatia

Location

Klinica bolnica Dubrava

Zagreb, 10000, Croatia

Location

Klinicki bolnicki centar Zagreb-Rebro

Zagreb, 10000, Croatia

Location

Opca bolnica "Sveti Duh"

Zagreb, 10000, Croatia

Location

Internistische Gemeinschaftspraxis

Augsburg, 86150, Germany

Location

Dr. Karlheinz Hehemann

Beckum, 59269, Germany

Location

Dr. Klaus Busch

Dortmund, 44137, Germany

Location

Medical Clinic and Policlinic 3

Giessen, 35392, Germany

Location

Diabetologische Schwerpunktpraxis

Hamburg, 21073, Germany

Location

IKFE GmbH

Mainz, 55119, Germany

Location

Institut for diabetic research

Munich, 80804, Germany

Location

Profil, Institut fur Stoffwechselstorungen

Neuss, 41460, Germany

Location

Dr. Thomas Behnke

Neuwied, 56564, Germany

Location

Dr. Bernd Donaubauer

Oschatz, 04758, Germany

Location

Marienhospital Osnabruck

Osnabrück, 49074, Germany

Location

Dr. Joerg Steindorf

Schkeuditz, 04435, Germany

Location

Dr. Jerzi Jasinski

Wiesbaden, 65183, Germany

Location

"Polyclinic" General Hospital of Athens

Athens, 10552, Greece

Location

Department of Endocrinology

Athens, 10676, Greece

Location

Diabetes Center

Athens, 11527, Greece

Location

University Hospital of Patras

Pátrai, 26500, Greece

Location

1st Internal Medicine Department "Papagergiou"

Thessaloniki, 56429, Greece

Location

Instituto di Endocrinologia

Catania, 95124, Italy

Location

Dipartimento di fisiopatologia clinica

Florence, 50134, Italy

Location

U.O. Medicina Generale

Milan, 60-20132, Italy

Location

Ospedale Civile di Padova

Padua, 35128, Italy

Location

Policlinico Univarsitario P. Giaccone

Palermo, 90127, Italy

Location

U.O. Universita di Malattie del Metabolismo e Diabetologia

Torino, Italy

Location

Gelre Ziekenhuizen

Apeldoorn, 7300 DS, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, 6815 AD, Netherlands

Location

Maxima Medisch Centrum Location Eindhoven

Eindhoven, 5631 BM, Netherlands

Location

Hospitais da Universidade de Coimbra

Coimbra, 3000-076, Portugal

Location

Hospital de Santo Andre

Leiria, 2410-197, Portugal

Location

Associacao Protectora dos Diabeticos de Portugal

Lisbon, 1250-203, Portugal

Location

Hospital Pedro Hispano

Matosinhos Municipality, 4454-509, Portugal

Location

Spitalul Judetean Brasov

Brasov, 500326, Romania

Location

Institutul de Diabet

Bucharest, 020475, Romania

Location

Spitalul Clinic nr. 1 Judetean

Judet Timis, 300723, Romania

Location

National Endocrinology Research Center

Moscow, 117036, Russia

Location

Setchenov Moscow Medical Academy

Moscow, 119881, Russia

Location

Moscow State Medical Stomatological

Moscow, 123448, Russia

Location

Russian Medical Academy for Advanced Medical Studies, Ministry of Health

Moscow, 125315, Russia

Location

Hospital of St. Elizabeth's

Saint Petersburg, 193257, Russia

Location

City Clinical Hospital #2

Saint Petersburg, 194354, Russia

Location

Medical Military Academy

Saint Petersburg, 198013, Russia

Location

Univerzitetni klinicni center Ljubljana

Ljubljana, 1000, Slovenia

Location

Splosna bolnisnica Maribor

Maribor, 2000, Slovenia

Location

Hospital Vega Baja

Alicante, 03300, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Endocrinology Service (Planta Baja)

Palma de Mallorca, 07198, Spain

Location

Hospital Virgen de Valme

Seville, 41014, Spain

Location

Hospital General de Teruel

Teruel, 44002, Spain

Location

Hospital la Ribera Alzira

Valencia, 46600 Alzira, Spain

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Tzu Chi General Hospital

Hualien City, Taiwan

Location

Veteran General Hospital-Taichung

Taichung, 407, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

Diabetes Research, Ward 34, Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Diabetes Unit, Blackburn Royal Infirmary

Blackburn, BB2 3LR, United Kingdom

Location

Colchester General Hospital

Colchester, CO4 5JL, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH3 9YW, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

Location

The Michael White Center for Diabetes and Endocrinology

Hull, HU3 2JZ, United Kingdom

Location

Clinical Sciences Centre

Liverpool, L7 8XP, United Kingdom

Location

Education Centre, James Cook University Hospital

Middlesbrough, TS4 3BW, United Kingdom

Location

Wellcome Labs, Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Queens Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

Diabetes Trial Unit OCDEM, Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Diabetes Unit, Gladsone Centre, Maelor Hospital

Wrexham, LL13 7TD, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 17160407 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 aspart, insulin aspart protamine drug combination 30:70; Insulin Aspart

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, Short-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 10, 2004
• Study Start: November 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

SL (2); RO (3); IT (6); ES (6); PT (4); NL (3); TW (4); GB (12); RU (7); CR (4); GR (5); DE (13)