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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

August 17, 2009
June 6, 2014
September 2009
August 2012   (final data collection date for primary outcome measure)
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).
To estimate the difference in change in HbA1c between 2 regimens: BET (basal insulin Glargine, Exenatide BID and metformin) and BBT (basal insulin Glargine, bolus insulin insulin TID and metformin). [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00960661 on ClinicalTrials.gov Archive Site
  • 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)
  • To compare the efficacy and safety between the BET and BBT regimens with respect to percentage of subjects with HbA1C ≤ 7.0% with minimum weight gain and with HbA1C ≤ 6.5% with minimum weight gain (≤ 1 kg). [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to percent of subjects with HbA1c ≤ 7.0% and ≤ 6.5%. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to fasting blood glucose (FBG). [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to 7-point self-monitored blood glucose (SMBG) profiles and daily mean blood glucose (BG) based on the 7-point SMBG profile. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to fasting glucagon. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to body weight and BMI. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to waist and hip circumference (cm). [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to insulin dose (24-hour total international units [IU] and total units/kg body weight). [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to seated systolic (SBP) and diastolic blood pressure (DBP). [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • To compare the efficacy and safety between the BET and BBT regimens with respect to various measures of safety. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: exenatide
    subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (26 weeks), twice a day
    Other Name: Byetta
  • Drug: insulin lispro
    titrated based on pre-meal glucose level; three times a day
    Other Name: Humalog
  • Drug: Metformin
  • Drug: Insulin/ Glargine
  • Experimental: Exenatide (BET)
    Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET)
    Interventions:
    • Drug: exenatide
    • Drug: Metformin
    • Drug: Insulin/ Glargine
  • Active Comparator: Insulin Lispro (BBT)
    Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT)
    Interventions:
    • Drug: insulin lispro
    • Drug: Metformin
    • Drug: Insulin/ Glargine
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 Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1036
August 2012
August 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Belgium,   Estonia,   Finland,   France,   Germany,   Greece,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Portugal,   Puerto Rico,   Romania,   Russian Federation,   Spain,   Sweden,   United Kingdom
 
NCT00960661
H8O-EW-GWDM
No
AstraZeneca
AstraZeneca
Eli Lilly and Company
Study Director: Chief Medical Officer, MD Eli Lilly and Company
AstraZeneca
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP