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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082407
• Other study ID #: H8O-MC-GWAD
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2004
• Last updated: March 19, 2015
• Start date: November 2003
• Est. completion date: July 2008

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCroatia: Agency for Medicinal Product and Medical DevicesGermany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesItaly: The Italian Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)Portugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencyRussia: Ministry of Health of the Russian FederationSlovenia: Agency for Medicinal Products - Ministry of HealthSpain: Spanish Agency of MedicinesTaiwan: Department of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 505
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• exenatide
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
• biphasic insulin aspart
subcutaneous injection, twice daily; titration to target blood glucose level

Locations

Country	Name	City	State
Croatia	Clinical Hospital Osijek	Osijek
Croatia	Klinica bolnica Dubrava	Zagreb
Croatia	Klinicki bolnicki centar Zagreb-Rebro	Zagreb
Croatia	Opca bolnica "Sveti Duh"	Zagreb
Germany	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	Osnabruck
Germany	Dr. Joerg Steindorf	Schkeuditz
Germany	Dr. Jerzi Jasinski	Wiesbaden
Greece	"Polyclinic" General Hospital of Athens	Athens
Greece	Department of Endocrinology	Athens
Greece	Diabetes Center	Athens
Greece	University Hospital of Patras	Patras
Greece	1st Internal Medicine Department "Papagergiou"	Thessaloniki
Italy	Instituto di Endocrinologia	Catania
Italy	Dipartimento di fisiopatologia clinica	Florence
Italy	U.O. Medicina Generale	Milan
Italy	Ospedale Civile di Padova	Padova
Italy	Policlinico Univarsitario P. Giaccone	Palermo
Italy	U.O. Universita di Malattie del Metabolismo e Diabetologia	Torino
Netherlands	Gelre Ziekenhuizen	Apeldoorn
Netherlands	Rijnstate Ziekenhuis	Arnhem
Netherlands	Maxima Medisch Centrum Location Eindhoven	Eindhoven
Portugal	Hospitais da Universidade de Coimbra	Coimbra
Portugal	Hospital de Santo Andre	Leiria
Portugal	Associacao Protectora dos Diabeticos de Portugal	Lisboa
Portugal	Hospital Pedro Hispano	Matosinhos
Romania	Spitalul Judetean Brasov	Brasov
Romania	Institutul de Diabet	Bucuresti
Romania	Spitalul Clinic nr. 1 Judetean	Judet Timis
Russian Federation	Moscow State Medical Stomatological	Moscow
Russian Federation	National Endocrinology Research Center	Moscow
Russian Federation	Russian Medical Academy for Advanced Medical Studies, Ministry of Health	Moscow
Russian Federation	Setchenov Moscow Medical Academy	Moscow
Russian Federation	City Clinical Hospital #2	St. Petersburg
Russian Federation	Hospital of St. Elizabeth's	St. Petersburg
Russian Federation	Medical Military Academy	St. Petersburg
Slovenia	Univerzitetni klinicni center Ljubljana	Ljubljana
Slovenia	Splosna bolnisnica Maribor	Maribor
Spain	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	Sevilla
Spain	Hospital General de Teruel	Teruel
Spain	Hospital la Ribera Alzira	Valencia
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Tzu Chi General Hospital	Hualien
Taiwan	Veteran General Hospital-Taichung	Taichung
Taiwan	Tri-Service General Hospital	Taipei
United Kingdom	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

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

Croatia,  Germany,  Greece,  Italy,  Netherlands,  Portugal,  Romania,  Russian Federation,  Slovenia,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

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-infe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glcosylated Hemoglobin (HbA1c)	Change in HbA1c from baseline to week 52	baseline, week 52	No
Secondary	Percentage of Patients Achieving HbA1c <=7%	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%).	52 weeks	No
Secondary	Change in Body Weight	Change in body weight from baseline to week 52.	baseline, week 52	No
Secondary	Change in Fasting Serum Glucose	Change in fasting serum glucose from baseline to week 52	baseline, week 52	No
Secondary	Change in 7-point Self-monitored Blood Glucose (SMBG) Profile	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	baseline, week 52	No
Secondary	Percentage of Patients With Hypoglycemic Events	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	52 weeks	No
Secondary	Change in Rate of Hypoglycemic Events	Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52	baseline, week 52	No