A Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes Who Were Previously Treated by Basal Insulin Glargine With Either Metformin or Metformin and Sulfonylurea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00960661
• Other study ID #: H8O-EW-GWDM
• Status: Completed
• Phase: Phase 3
• First received: August 17, 2009
• Last updated: March 19, 2015
• Start date: September 2009
• Est. completion date: August 2012

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: 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 AgencySpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyFinland: Finnish Medicines AgencyEstonia: Ravimiamet, Estonian State Agency of MedicinesKorea: Korea Food and Drug AdministrationRussia: Ministry of Health of Russian FederationArgentina: ANMAT (Administración Nacional de Medicamentos, Alimentos, y Tecnología Médica)Mexico: COFEPRIS (Comisión Federal para la Protección contra Riesgos Sanitarios)
• Study type: Interventional

Clinical Trial Summary

The study will compare two combination therapies: 1) Combined Basal Insulin Glargine (once a day), Exenatide (twice a day), and Metformin Therapy; or 2) Combined Basal Insulin Glargine (once a day), Bolus Insulin Lispro (three times a day), and Metformin Therapy, in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1036
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have been taking a basal insulin Glargine, at dose of = 20 units/day, for at least 3 months prior to study start.

• Have been taking basal insulin Glargine at dose of = 20 units/day, in combination with 1 of the following oral antidiabetic medication (OAM) regimens, for at least 3 months prior to study start:

• Metformin or immediate-release metformin or extended-release metformin alone at a maximum tolerated and stable dose with no less than 500 mg/day for at least 6 weeks prior to study start; or

• Metformin or immediate-release metformin or extended-release metformin at a maximum tolerated and stable dose with no less than 500 mg/day for at least 6 weeks prior to study start and sulfonylurea at a stable dose for 6 weeks prior to study start.

• Have an HbA1C > 7.0% and = 10.0%.

• Have a body mass index (BMI) between = 25 and = 45 kg/m2.

Exclusion Criteria:

• Are currently taking OAM that is not described above and not allowed with concurrent use of insulin per local product label.

• Have taken more than 1 week within 1 month prior to the study start any glucose-lowering medications not included above either alone or in combination formulations, or have used a drug for weight loss (for example, prescription drugs such as orlistat, sibutramine, phenylpropanolamine, rimonabant or similar over-the-counter medications).

• Have taken any insulin other than Glargine within the 3 months prior to study start for more than 1 week.

• Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, and inhaled preparations) within 4 weeks prior to the study start.

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.

• Have previously completed or been withdrawn from this study after enrollment.

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 (4 weeks) followed by 10mcg (26 weeks), twice a day
• insulin lispro
titrated based on pre-meal glucose level; three times a day
• Metformin

• Insulin/ Glargine

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Capital Federal
Argentina	Research Site	Ciudad Autonoma de Buenos Aire
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Corrientes
Argentina	Research Site	Rosario
Argentina	Research Site	San Rafael
Belgium	Research Site	Arlon
Belgium	Research Site	Bonheiden
Belgium	Research Site	Edegem
Belgium	Research Site	Merksem
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
Finland	Research Site	Helsinki
Finland	Research Site	Oulu
Finland	Research Site	Vantaa
France	Research Site	Angers
France	Research Site	Auxerre
France	Research Site	Bar Le Duc
France	Research Site	Douai Cedex
France	Research Site	La Roche Sur Yon
France	Research Site	La Rochelle Cedex 1
France	Research Site	Le Creuzot
France	Research Site	Lille Cedex
France	Research Site	Marseille Cedex 20
France	Research Site	Montpellier Cedex 5
France	Research Site	Nanterre
France	Research Site	Pessac Cedex
France	Research Site	Rennes Cedex 2
France	Research Site	Strasbourg
France	Research Site	Toulouse Cedex 9
France	Research Site	Venissieux
Germany	Research Site	Bad Lauterberg
Germany	Research Site	Dippoldiswalde
Germany	Research Site	Friedrichsthal
Germany	Research Site	Goch
Germany	Research Site	Grevenbroich
Germany	Research Site	Hamburg
Germany	Research Site	Mainz
Germany	Research Site	Saarbruecken
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Italy	Research Site	Firenze
Italy	Research Site	Napoli
Italy	Research Site	Olbia
Italy	Research Site	Perugia
Italy	Research Site	Trieste
Italy	Research Site	Verona
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Ulsan-Si
Korea, Republic of	Research Site	Wonju-Si
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Cuernavaca
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey
Netherlands	Research Site	Almere
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Beek
Netherlands	Research Site	Den Haag
Netherlands	Research Site	Groningen
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Hoogeveen
Netherlands	Research Site	Sittard-Geleen
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisbon
Portugal	Research Site	Portugal
Puerto Rico	Research Site	Hato Rey
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Constanta
Romania	Research Site	Craiova
Romania	Research Site	Oradea
Romania	Research Site	Ploiesti
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	St. Petersburg
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Dos Hermanas
Spain	Research Site	La Coruna
Spain	Research Site	Santander
Spain	Research Site	Valencia
Sweden	Research Site	Halmstad
Sweden	Research Site	Karlstad
Sweden	Research Site	Lund
Sweden	Research Site	Malmo
Sweden	Research Site	Solna
Sweden	Research Site	Stockholm
Sweden	Research Site	Umea
United Kingdom	Research Site	Bournemouth
United Kingdom	Research Site	Ipswich
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Penarth
United Kingdom	Research Site	Wakefield

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

Argentina,  Belgium,  Estonia,  Finland,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Ca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 30	Change in HbA1c from baseline following 30 weeks of therapy (i.e. HbA1c at week 30 minus HbA1c at baseline).	Baseline, 30 weeks	No
Secondary	Percentage of Participants Achieving HbA1C < 7.0%	Percentage of participants achieving HbA1C < 7.0%	Week 30	No
Secondary	Percent of Participants Achieving HbA1c = 6.5%.	Percent of participants achieving HbA1c = 6.5%.	Week 30	No
Secondary	Change in Fasting Blood Glucose (FBG) From Baseline to Week 30.	Change in fasting blood glucose (FBG) from Baseline to Week 30 using MMRM model. The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.	Baseline, Week 30	No
Secondary	Change in Total Cholesterol From Baseline to Week 30	Change in total cholesterol from baseline to Week 30 using ANCOVA model. The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate.	Baseline, week 30	No
Secondary	Change in High Density Lipoprotein (HDL) From Baseline to Week 30	Change in High Density Lipoprotein (HDL) from baseline to Week 30 using ANCOVA model.The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate.	Baseline, week 30	No
Secondary	Change in Low Density Lipoprotein (LDL) From Baseline to Week 30	Change in Low Density Lipoprotein (LDL) from baseline to week 30 using ANCOVA model.The model included the respective secondary outcome as dependent variable, country, prior use of SU's and treatment groups as factors, and the respective outcomes baseline value as a covariate.	Baseline, Week 30	No
Secondary	Change in Body Weight From Baseline to Week 30.	Change in body weight from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.	baseline, week 30	No
Secondary	Change in Systolic Blood Pressure (SBP) From Baseline to Week 30	Change in Systolic Blood Pressure (SBP) from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.	Baseline, Week 30	No
Secondary	Change in Diastolic Blood Pressure (DBP) From Baseline to Week 30	Change in Diastolic Blood Pressure (DBP) from baseline to Week 30 using MMRM model.The model included the respective baseline outcome as covariate, treatment, country, prior use of SUs, week of visit, and treatment-by-week interaction as fixed effects and patient and error as random effects.	baseline, Week 30	No
Secondary	Daily Insulin Glargine Dose at Baseline and at Week 30	Daily Insulin Glargine Dose at baseline and at Week 30	Baseline, week 30	No
Secondary	Major Hypoglycemia Rate Per Year	Mean (standard deviation) of major hyperglycemia episodes experienced per year. Rates per year were calculated for each individual as the number of episodes divided by the total number of days in the study (from randomization to last visit date), then multiplied by 365.25. Major hypoglycemia was defined as any symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and requiring the assistance of another person because of severe impairment in consciousness or behavior.	30 weeks	Yes
Secondary	Minor Hypoglycemia Rate Per Year	Mean (standard deviation) of minor hyperglycemia episodes experienced per year. Rates per year were calculated for each individual as the number of episodes divided by the total number of days in the study (from randomization to last visit date), then multiplied by 365.25. Minor hypoglycemia was defined as any time a participant feels that he or she is experiencing a sign or symptom associated with hypoglycemia that is either self-treated by the participant or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL)	30 weeks	Yes