Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Long Term Treatment With Exenatide Versus Glimepiride in Patients With Type 2 Diabetes Pretreated With Metformin (EUREXA: European Exenatide Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00359762
• Other study ID #: H8O-EW-GWBE
• Status: Completed
• Phase: Phase 3
• First received: July 31, 2006
• Last updated: August 17, 2015
• Start date: September 2006
• Est. completion date: March 2011

Study information

• Verified date: August 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and WomenCzech Republic: State Institute for Drug ControlFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: The Italian Medicines AgencyMexico: Ministry of HealthPoland: Ministry of HealthSpain: Spanish Agency of MedicinesSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIreland: Irish Medical Board
• Study type: Interventional

Clinical Trial Summary

This study assesses the effects of twice-daily subcutaneous injection exenatide versus treatment with sulfonylurea (glimepiride) on long-term glycemic control and beta-cell function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1029
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Diagnosed with type 2 diabetes mellitus.

• Treated with diet and exercise and a stable, maximally tolerated dose of metformin for at least 3 months prior to screening.

• HbA1c >=6.5% and <=9.0%.

• Body Mass Index (BMI) >=25 kg/m^2 and <40 kg/m^2.

Exclusion Criteria:

• Participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening.

• Characteristics contraindicating metformin or glimepiride use.

• Receiving drugs that directly affect gastrointestinal motility.

• Receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy.

• Have used any prescription drug to promote weight loss within 3 months prior to screening.

• Treated for longer than 2 weeks with any of the following medications within 3 months prior to screening: *insulin; *thiazolidinediones; *alpha-glucosidase inhibitors; *sulfonylurea; *meglitinides

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
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide
subcutaneous injection (5mcg or 10mcg), twice a day
• glimepiride
oral tablet (titrated to maximally tolerated dose), once daily

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Salzburg
Austria	Research Site	Vienna
Czech Republic	Research Site	Beroun
Czech Republic	Research Site	Ceske Budejovice
Czech Republic	Research Site	Hradec Kralove
Czech Republic	Research Site	Liberec
Czech Republic	Research Site	Pisek
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Trebic
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Finland	Research Site	Pori
Finland	Research Site	Vaasa
France	Research Site	Alencon
France	Research Site	Bois-Guillaume
France	Research Site	Bourg des Comptes
France	Research Site	Broglie
France	Research Site	Bron
France	Research Site	Fleville Devant Nancy
France	Research Site	Le Creusot
France	Research Site	Le Mans
France	Research Site	Loudun
France	Research Site	Montigny les Metz
France	Research Site	Nevers
France	Research Site	Strasbourg
France	Research Site	Thouars
France	Research Site	Tours
France	Research Site	Valreas
France	Research Site	Vénissieux
France	Research Site	Vihiers
Germany	Research Site	Aschaffenburg
Germany	Research Site	Dresden
Germany	Research Site	Eisenach
Germany	Research Site	Essen
Germany	Research Site	Essen Schonnebeck
Germany	Research Site	Falkensee
Germany	Research Site	Fulda
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg-Altona
Germany	Research Site	Hamburg-Ottmarschen
Germany	Research Site	Heidelberg
Germany	Research Site	Leipzig
Germany	Research Site	Munster
Germany	Research Site	Saarbrucken
Germany	Research Site	Schenklengsfeld
Germany	Research Site	Schkeuditz
Germany	Research Site	St. Ingbert
Germany	Research Site	Staffelstein
Germany	Research Site	Witten
Hungary	Research Site	Budapest
Hungary	Research Site	Gyula
Hungary	Research Site	Kecskemet
Hungary	Research Site	Veszprem
Hungary	Research Site	Zalaegerszeg
Ireland	Research Site	County Galway
Ireland	Research Site	County Waterford
Ireland	Research Site	Dublin
Israel	Research Site	Haifa
Israel	Research Site	Holon
Israel	Research Site	Jerusalem
Israel	Research Site	Tel Hashomer
Italy	Research Site	Ancona
Italy	Research Site	Arenzano
Italy	Research Site	Atri
Italy	Research Site	Bergamo
Italy	Research Site	Catanzaro
Italy	Research Site	Firenze
Italy	Research Site	Foggia
Italy	Research Site	Forli
Italy	Research Site	Genova
Italy	Research Site	Grosseto
Italy	Research Site	Milano
Italy	Research Site	Monserrato (Cagliari)
Italy	Research Site	Napoli
Italy	Research Site	Palermo
Italy	Research Site	Perugia
Italy	Research Site	Pescara
Italy	Research Site	Pisa
Italy	Research Site	Ravenna
Italy	Research Site	Roma
Italy	Research Site	San Benedetto del Tronto
Italy	Research Site	Siena
Italy	Research Site	Treviso
Italy	Research Site	Verona
Mexico	Research Site	Celaya	Guanajuato
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Monterrey	Nuevo Leon
Mexico	Research Site	Pachuca	Hidalgo
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Lublin
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Switzerland	Research Site	Fribourg
Switzerland	Research Site	Geneva
Switzerland	Research Site	Geneve
Switzerland	Research Site	Lausanne
Switzerland	Research Site	Luzern
United Kingdom	Research Site	Bath
United Kingdom	Research Site	Belfast
United Kingdom	Research Site	Brandford on Avon
United Kingdom	Research Site	County Antrim
United Kingdom	Research Site	Downpatrick
United Kingdom	Research Site	Frome
United Kingdom	Research Site	Midsomer Norton
United Kingdom	Research Site	Omagh
United Kingdom	Research Site	Penzance
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Southdown
United Kingdom	Research Site	Wiltshire

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

Austria,  Czech Republic,  Finland,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Mexico,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Treatment Failure	Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.	Baseline to end of Period II (up to 4.5 years)	No
Primary	Time to Treatment Failure	Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.	Baseline to end of Period II (up to 4.5 years)	No
Secondary	Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3	HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) - 3.5) x 7.175).	Year 3 in Period II	No
Secondary	Change in HOMA-B From Baseline to Endpoint	Change in HOMA-B from baseline to endpoint.	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Fasting Proinsulin/Insulin Ratio at Year 3	Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3.	Year 3 in Period II	No
Secondary	Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.	Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint.	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3	DI30/DG30 at Year 3. DI30/DG30 ratio was calculated as (30 minute post prandial insulin - fasting insulin) (measured in pmol/L)/(30 minute post prandial glucose - fasting glucose) (measured in mmol/L).	Year 3 in Period II	No
Secondary	Change in DI30/DG30 Ratio From Baseline to Endpoint	Change in DI30/DG30 ratio from baseline to endpoint.	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Disposition Index at Year 3	Disposition Index at Year 3. Disposition index was calculated as (DI30/DG30 ratio)/(HOMA index for insulin resistance (HOMA-IR)); where HOMA-IR=(fasting insulin (measured in pmol/L) x fasting glucose (measured in mmol/L))/(22.5 x 7.175).	Year 3 in Period II	No
Secondary	Change in Disposition Index From Baseline to Endpoint	Change in disposition index from baseline to endpoint.	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Change in HbA1c From Baseline to Year 3	Change in HbA1c from baseline to Year 3.	Baseline, Year 3 in Period II	No
Secondary	Change in HbA1c From Baseline to Endpoint	Change in HbA1c from baseline to endpoint. Endpoint for HbA1c was defined as the HbA1c measured at the treatment failure for patients reaching primary endpoint and was the last observation in study period II for other patients (either followed until the end of the study period II or discontinuing the study).	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Fasting Plasma Glucose at Year 3	Fasting plasma glucose at Year 3.	Year 3 in Period II	No
Secondary	Change in Fasting Plasma Glucose From Baseline to Endpoint	Change in fasting plasma glucose from baseline to endpoint.	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Postprandial (2 Hours) Plasma Glucose at Year 3	Postprandial (2 hours) plasma glucose at Year 3.	Year 3 in Period II	No
Secondary	Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint	Change from baseline in postprandial (2 hours) plasma glucose to endpoint.	Baseline, end of Period II (up to 4.5 years)	No
Secondary	Change in Body Weight From Baseline to Year 3	Change in Body weight from baseline to Year 3.	Baseline, Year 3 in Period II	No
Secondary	Systolic Blood Pressure at Year 3	Systolic Blood pressure at Year 3.	Year 3 in Period II	No
Secondary	Diastolic Blood Pressure at Year 3	Diastolic Blood pressure at Year 3.	Year 3 in Period II	No
Secondary	Heart Rate at Year 3	Heart rate at Year 3.	Year 3 in Period II	No
Secondary	Triglycerides at Year 3	Triglycerides at Year 3.	Year 3 in Period II	No
Secondary	Total Cholesterol at Year 3	Total Cholesterol at Year 3.	Year 3 in Period II	No
Secondary	High-density Lipoprotein (HDL) Cholesterol at Year 3	HDL Cholesterol at Year 3.	Year 3 in Period II	No
Secondary	Hypoglycemia Rate Per Year	All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.	Baseline to end of Period II (up to 4.5 years)	No
Secondary	Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III	Change in HbA1c from baseline to Year 2.	Baseline in Period III, Year 2 in Period III	No
Secondary	Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III	Change in HbA1c from baseline to Year 2.	Baseline in Period III, Year 2 in Period III	No
Secondary	Hypoglycemia Rate Per Year in Period III	All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.	Start of Period III to end of study	No