MedPath

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

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT00082407
Lead Sponsor
AstraZeneca
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
505
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Biphasic Insulin Aspart Armbiphasic insulin aspartsubcutaneous injection, twice daily; titration to target blood glucose level
Exenatide Armexenatidesubcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
Primary Outcome Measures
NameTimeMethod
Change in Glcosylated Hemoglobin (HbA1c)baseline, week 52

Change in HbA1c from baseline to week 52

Secondary Outcome Measures
NameTimeMethod
Percentage of Patients Achieving HbA1c <=7%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%).

Change in Body Weightbaseline, week 52

Change in body weight from baseline to week 52.

Change in 7-point Self-monitored Blood Glucose (SMBG) Profilebaseline, 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

Change in Fasting Serum Glucosebaseline, week 52

Change in fasting serum glucose from baseline to week 52

Percentage of Patients With Hypoglycemic Events52 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

Change in Rate of Hypoglycemic Eventsbaseline, week 52

Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52

Trial Locations

Locations (69)

Hospital Pedro Hispano

🇵🇹

Matosinhos, Portugal

Clinical Hospital Osijek

🇭🇷

Osijek, Croatia

Klinica bolnica Dubrava

🇭🇷

Zagreb, Croatia

Klinicki bolnicki centar Zagreb-Rebro

🇭🇷

Zagreb, Croatia

Internistische Gemeinschaftspraxis

🇩🇪

Augsburg, Germany

Opca bolnica "Sveti Duh"

🇭🇷

Zagreb, Croatia

Dr. Karlheinz Hehemann

🇩🇪

Beckum, Germany

Dr. Klaus Busch

🇩🇪

Dortmund, Germany

Diabetologische Schwerpunktpraxis

🇩🇪

Hamburg, Germany

Medical Clinic and Policlinic 3

🇩🇪

Giessen, Germany

Dr. Bernd Donaubauer

🇩🇪

Oschatz, Germany

IKFE GmbH

🇩🇪

Mainz, Germany

Institut for diabetic research

🇩🇪

Munich, Germany

Profil, Institut fur Stoffwechselstorungen

🇩🇪

Neuss, Germany

Dr. Thomas Behnke

🇩🇪

Neuwied, Germany

Marienhospital Osnabruck

🇩🇪

Osnabruck, Germany

Dr. Joerg Steindorf

🇩🇪

Schkeuditz, Germany

Dr. Jerzi Jasinski

🇩🇪

Wiesbaden, Germany

"Polyclinic" General Hospital of Athens

🇬🇷

Athens, Greece

Diabetes Center

🇬🇷

Athens, Greece

University Hospital of Patras

🇬🇷

Patras, Greece

Department of Endocrinology

🇬🇷

Athens, Greece

1st Internal Medicine Department "Papagergiou"

🇬🇷

Thessaloniki, Greece

Ospedale Civile di Padova

🇮🇹

Padova, Italy

Rijnstate Ziekenhuis

🇳🇱

Arnhem, Netherlands

Instituto di Endocrinologia

🇮🇹

Catania, Italy

Dipartimento di fisiopatologia clinica

🇮🇹

Florence, Italy

Gelre Ziekenhuizen

🇳🇱

Apeldoorn, Netherlands

U.O. Medicina Generale

🇮🇹

Milan, Italy

Policlinico Univarsitario P. Giaccone

🇮🇹

Palermo, Italy

U.O. Universita di Malattie del Metabolismo e Diabetologia

🇮🇹

Torino, Italy

Maxima Medisch Centrum Location Eindhoven

🇳🇱

Eindhoven, Netherlands

Institutul de Diabet

🇷🇴

Bucuresti, Romania

Associacao Protectora dos Diabeticos de Portugal

🇵🇹

Lisboa, Portugal

Hospitais da Universidade de Coimbra

🇵🇹

Coimbra, Portugal

Spitalul Judetean Brasov

🇷🇴

Brasov, Romania

Hospital de Santo Andre

🇵🇹

Leiria, Portugal

National Endocrinology Research Center

🇷🇺

Moscow, Russian Federation

Spitalul Clinic nr. 1 Judetean

🇷🇴

Judet Timis, Romania

Setchenov Moscow Medical Academy

🇷🇺

Moscow, Russian Federation

Moscow State Medical Stomatological

🇷🇺

Moscow, Russian Federation

Russian Medical Academy for Advanced Medical Studies, Ministry of Health

🇷🇺

Moscow, Russian Federation

Hospital of St. Elizabeth's

🇷🇺

St. Petersburg, Russian Federation

City Clinical Hospital #2

🇷🇺

St. Petersburg, Russian Federation

Medical Military Academy

🇷🇺

St. Petersburg, Russian Federation

Splosna bolnisnica Maribor

🇸🇮

Maribor, Slovenia

Univerzitetni klinicni center Ljubljana

🇸🇮

Ljubljana, Slovenia

Hospital Vega Baja

🇪🇸

Alicante, Spain

Hospital Clinic i Provincial de Barcelona

🇪🇸

Barcelona, Spain

Hospital General de Teruel

🇪🇸

Teruel, Spain

Hospital la Ribera Alzira

🇪🇸

Valencia, Spain

Changhua Christian Hospital

🇨🇳

Changhua, Taiwan

Tzu Chi General Hospital

🇨🇳

Hualien, Taiwan

Diabetes Research, Ward 34, Birmingham Heartlands Hospital

🇬🇧

Birmingham, United Kingdom

Veteran General Hospital-Taichung

🇨🇳

Taichung, Taiwan

Tri-Service General Hospital

🇨🇳

Taipei, Taiwan

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

Endocrinology Service (Planta Baja)

🇪🇸

Palma de Mallorca, Spain

Hospital Virgen de Valme

🇪🇸

Sevilla, Spain

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