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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00082407
Recruitment Status : Completed
First Posted : May 10, 2004
Results First Posted : July 31, 2013
Last Update Posted : April 7, 2015
Eli Lilly and Company
Information provided by (Responsible Party):

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).

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: exenatide Drug: biphasic insulin aspart Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 505 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Exenatide (AC2993, Synthetic Exendin-4, LY2148568) Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin
Study Start Date : November 2003
Actual Primary Completion Date : July 2008
Actual Study Completion Date : July 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Exenatide Arm
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
Drug: exenatide
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
Other Name: Byetta

Active Comparator: Biphasic Insulin Aspart Arm
subcutaneous injection, twice daily; titration to target blood glucose level
Drug: biphasic insulin aspart
subcutaneous injection, twice daily; titration to target blood glucose level
Other Name: NovoLog

Primary Outcome Measures :
  1. Change in Glcosylated Hemoglobin (HbA1c) [ Time Frame: baseline, week 52 ]
    Change in HbA1c from baseline to week 52

Secondary Outcome Measures :
  1. Percentage of Patients Achieving HbA1c <=7% [ Time Frame: 52 weeks ]
    Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 52 (percentage = [number of subjects with HbA1c <=7% at week 52 divided by number of subjects with HbA1c >7% at baseline] * 100%).

  2. Change in Body Weight [ Time Frame: baseline, week 52 ]
    Change in body weight from baseline to week 52.

  3. Change in Fasting Serum Glucose [ Time Frame: baseline, week 52 ]
    Change in fasting serum glucose from baseline to week 52

  4. Change in 7-point Self-monitored Blood Glucose (SMBG) Profile [ Time Frame: baseline, week 52 ]
    Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52

  5. Percentage of Patients With Hypoglycemic Events [ Time Frame: 52 weeks ]
    Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study

  6. Change in Rate of Hypoglycemic Events [ Time Frame: baseline, week 52 ]
    Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00082407

  Hide Study Locations
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Clinical Hospital Osijek
Osijek, Croatia, 31000
Klinica bolnica Dubrava
Zagreb, Croatia, 10000
Klinicki bolnicki centar Zagreb-Rebro
Zagreb, Croatia, 10000
Opca bolnica "Sveti Duh"
Zagreb, Croatia, 10000
Internistische Gemeinschaftspraxis
Augsburg, Germany, 86150
Dr. Karlheinz Hehemann
Beckum, Germany, 59269
Dr. Klaus Busch
Dortmund, Germany, 44137
Medical Clinic and Policlinic 3
Giessen, Germany, 35392
Diabetologische Schwerpunktpraxis
Hamburg, Germany, 21073
Mainz, Germany, 55119
Institut for diabetic research
Munich, Germany, 80804
Profil, Institut fur Stoffwechselstorungen
Neuss, Germany, 41460
Dr. Thomas Behnke
Neuwied, Germany, 56564
Dr. Bernd Donaubauer
Oschatz, Germany, 04758
Marienhospital Osnabruck
Osnabruck, Germany, 49074
Dr. Joerg Steindorf
Schkeuditz, Germany, 04435
Dr. Jerzi Jasinski
Wiesbaden, Germany, 65183
"Polyclinic" General Hospital of Athens
Athens, Greece, 10552
Department of Endocrinology
Athens, Greece, 10676
Diabetes Center
Athens, Greece, 11527
University Hospital of Patras
Patras, Greece, 26500
1st Internal Medicine Department "Papagergiou"
Thessaloniki, Greece, 56429
Instituto di Endocrinologia
Catania, Italy, 95124
Dipartimento di fisiopatologia clinica
Florence, Italy, 50134
U.O. Medicina Generale
Milan, Italy, 60-20132
Ospedale Civile di Padova
Padova, Italy, 35128
Policlinico Univarsitario P. Giaccone
Palermo, Italy, 90127
U.O. Universita di Malattie del Metabolismo e Diabetologia
Torino, Italy
Gelre Ziekenhuizen
Apeldoorn, Netherlands, 7300 DS
Rijnstate Ziekenhuis
Arnhem, Netherlands, 6815 AD
Maxima Medisch Centrum Location Eindhoven
Eindhoven, Netherlands, 5631 BM
Hospitais da Universidade de Coimbra
Coimbra, Portugal, 3000-076
Hospital de Santo Andre
Leiria, Portugal, 2410-197
Associacao Protectora dos Diabeticos de Portugal
Lisboa, Portugal, 1250-203
Hospital Pedro Hispano
Matosinhos, Portugal, 4454-509
Spitalul Judetean Brasov
Brasov, Romania, 500326
Institutul de Diabet
Bucuresti, Romania, 020475
Spitalul Clinic nr. 1 Judetean
Judet Timis, Romania, 300723
Russian Federation
National Endocrinology Research Center
Moscow, Russian Federation, 117036
Setchenov Moscow Medical Academy
Moscow, Russian Federation, 119881
Moscow State Medical Stomatological
Moscow, Russian Federation, 123448
Russian Medical Academy for Advanced Medical Studies, Ministry of Health
Moscow, Russian Federation, 125315
Hospital of St. Elizabeth's
St. Petersburg, Russian Federation, 193257
City Clinical Hospital #2
St. Petersburg, Russian Federation, 194354
Medical Military Academy
St. Petersburg, Russian Federation, 198013
Univerzitetni klinicni center Ljubljana
Ljubljana, Slovenia, 1000
Splosna bolnisnica Maribor
Maribor, Slovenia, 2000
Hospital Vega Baja
Alicante, Spain, 03300
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Endocrinology Service (Planta Baja)
Palma de Mallorca, Spain, 07198
Hospital Virgen de Valme
Sevilla, Spain, 41014
Hospital General de Teruel
Teruel, Spain, 44002
Hospital la Ribera Alzira
Valencia, Spain, 46600 Alzira
Changhua Christian Hospital
Changhua, Taiwan, 500
Tzu Chi General Hospital
Hualien, Taiwan
Veteran General Hospital-Taichung
Taichung, Taiwan, 407
Tri-Service General Hospital
Taipei, Taiwan
United Kingdom
Diabetes Research, Ward 34, Birmingham Heartlands Hospital
Birmingham, United Kingdom, B9 5SS
Diabetes Unit, Blackburn Royal Infirmary
Blackburn, United Kingdom, BB2 3LR
Colchester General Hospital
Colchester, United Kingdom, CO4 5JL
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom, EH3 9YW
Glasgow Royal Infirmary
Glasgow, United Kingdom, G4 0SF
The Michael White Center for Diabetes and Endocrinology
Hull, United Kingdom, HU3 2JZ
Clinical Sciences Centre
Liverpool, United Kingdom, L7 8XP
Education Centre, James Cook University Hospital
Middlesbrough, United Kingdom, TS4 3BW
Wellcome Labs, Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom, NE1 4LP
Queens Medical Centre
Nottingham, United Kingdom, NG7 2UH
Diabetes Trial Unit OCDEM, Churchill Hospital
Oxford, United Kingdom, OX3 7LJ
Diabetes Unit, Gladsone Centre, Maelor Hospital
Wrexham, United Kingdom, LL13 7TD
Sponsors and Collaborators
Eli Lilly and Company
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Study Director: Chief Medical Officer, MD Eli Lilly and Company

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: AstraZeneca Identifier: NCT00082407     History of Changes
Other Study ID Numbers: H8O-MC-GWAD
First Posted: May 10, 2004    Key Record Dates
Results First Posted: July 31, 2013
Last Update Posted: April 7, 2015
Last Verified: March 2015
Keywords provided by AstraZeneca:
insulin aspart
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin Aspart
Insulin, Long-Acting
Insulin degludec, insulin aspart drug combination
Biphasic Insulins
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Hormones, Hormone Substitutes, and Hormone Antagonists