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

Overview[ - collapse ][ - ]

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.
ConditionType 2 Diabetes Mellitus
InterventionDrug: exenatide
Drug: insulin lispro
Drug: Metformin
Drug: Insulin/ Glargine
PhasePhase 3
SponsorBristol-Myers Squibb
Responsible PartyBristol-Myers Squibb
ClinicalTrials.gov IdentifierNCT00960661
First ReceivedAugust 17, 2009
Last UpdatedNovember 21, 2013
Last verifiedNovember 2013

Tracking Information[ + expand ][ + ]

First Received DateAugust 17, 2009
Last Updated DateNovember 21, 2013
Start DateSeptember 2009
Estimated Primary Completion DateAugust 2012
Current Primary Outcome MeasuresChange 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).
Current 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)

Descriptive Information[ + expand ][ + ]

Brief TitleA 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
Official TitleA 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
Brief 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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionType 2 Diabetes Mellitus
InterventionDrug: exenatide
subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (26 weeks), twice a day
Other Names:
ByettaDrug: insulin lispro
titrated based on pre-meal glucose level; three times a day
Other Names:
HumalogDrug: Metformin
Drug: Insulin/ Glargine
Study Arm (s)
  • Experimental: Exenatide (BET)
    Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET)
  • Active Comparator: Insulin Lispro (BBT)
    Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT)

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment1036
Estimated Completion DateAugust 2012
Estimated Primary Completion DateAugust 2012
Eligibility 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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Argentina, Belgium, Estonia, Finland, France, Germany, Greece, Italy, Korea, Republic of, Mexico, Netherlands, Portugal, Puerto Rico, Romania, Russian Federation, Spain, Sweden, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00960661
Other Study ID NumbersH8O-EW-GWDM
Has Data Monitoring CommitteeNo
Information Provided ByBristol-Myers Squibb
Study SponsorBristol-Myers Squibb
CollaboratorsEli Lilly and Company
Investigators Study Director: Chief Medical Officer, MD Eli Lilly and Company
Verification DateNovember 2013

Locations[ + expand ][ + ]

Research Site
Buenos Aires, Argentina
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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
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Arlon, Belgium
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Bonheiden, Belgium
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Edegem, Belgium
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Merksem, Belgium
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Tallinn, Estonia
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Tartu, Estonia
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Helsinki, Finland
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Oulu, Finland
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Vantaa, Finland
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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
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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
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Athens, Greece
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Thessaloniki, Greece
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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
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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
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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
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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
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Coimbra, Portugal
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Lisboa, Portugal
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Lisbon, Portugal
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Portugal, Portugal
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Hato Rey, Puerto Rico
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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
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Arkhangelsk, Russian Federation
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Rostov-on-Don, Russian Federation
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St. Petersburg, Russian Federation
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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
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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
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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
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Wakefield, United Kingdom