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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00960661
First received: August 17, 2009
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: exenatide
Drug: insulin lispro
Drug: Metformin
Drug: Insulin/ Glargine
Phase 3

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 30 [ Time Frame: Baseline, 30 weeks ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline following 30 weeks of therapy (i.e. HbA1c at week 30 minus HbA1c at baseline).


Secondary Outcome Measures:
  • Percentage of Participants Achieving HbA1C < 7.0% [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    Percentage of participants achieving HbA1C < 7.0%

  • Percent of Participants Achieving HbA1c ≤ 6.5%. [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    Percent of participants achieving HbA1c ≤ 6.5%.

  • Change in Fasting Blood Glucose (FBG) From Baseline to Week 30. [ Time Frame: Baseline, Week 30 ] [ Designated as safety issue: No ]
    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.

  • Change in Total Cholesterol From Baseline to Week 30 [ Time Frame: Baseline, week 30 ] [ Designated as safety issue: No ]
    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.

  • Change in High Density Lipoprotein (HDL) From Baseline to Week 30 [ Time Frame: Baseline, week 30 ] [ Designated as safety issue: No ]
    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.

  • Change in Low Density Lipoprotein (LDL) From Baseline to Week 30 [ Time Frame: Baseline, Week 30 ] [ Designated as safety issue: No ]
    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.

  • Change in Body Weight From Baseline to Week 30. [ Time Frame: baseline, week 30 ] [ Designated as safety issue: No ]
    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.

  • Change in Systolic Blood Pressure (SBP) From Baseline to Week 30 [ Time Frame: Baseline, Week 30 ] [ Designated as safety issue: No ]
    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.

  • Change in Diastolic Blood Pressure (DBP) From Baseline to Week 30 [ Time Frame: baseline, Week 30 ] [ Designated as safety issue: No ]
    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.

  • Daily Insulin Glargine Dose at Baseline and at Week 30 [ Time Frame: Baseline, week 30 ] [ Designated as safety issue: No ]
    Daily Insulin Glargine Dose at baseline and at Week 30

  • Major Hypoglycemia Rate Per Year [ Time Frame: 30 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Minor Hypoglycemia Rate Per Year [ Time Frame: 30 weeks ] [ Designated as safety issue: Yes ]
    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)


Enrollment: 1036
Study Start Date: September 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide (BET)
Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET)
Drug: exenatide
subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (26 weeks), twice a day
Other Name: Byetta
Drug: Metformin Drug: Insulin/ Glargine
Active Comparator: Insulin Lispro (BBT)
Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT)
Drug: insulin lispro
titrated based on pre-meal glucose level; three times a day
Other Name: Humalog
Drug: Metformin Drug: Insulin/ Glargine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00960661

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

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00960661     History of Changes
Other Study ID Numbers: H8O-EW-GWDM
Study First Received: August 17, 2009
Results First Received: September 5, 2013
Last Updated: June 6, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: The Italian Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Finland: Finnish Medicines Agency
Estonia: Ravimiamet, Estonian State Agency of Medicines
Korea: Korea Food and Drug Administration
Russia: Ministry of Health of Russian Federation
Argentina: ANMAT (Administración Nacional de Medicamentos, Alimentos, y Tecnología Médica)
Mexico: COFEPRIS (Comisión Federal para la Protección contra Riesgos Sanitarios)

Keywords provided by AstraZeneca:
diabetes
exenatide
Byetta
insulin lispro
Humalog
insulin glargine
Lantus
Amylin
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Glargine
Exenatide
Insulin
Metformin
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 16, 2014