A Study to Determine the Safety and Efficacy of Albiglutide in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00838916
First received: February 5, 2009
Last updated: May 22, 2014
Last verified: April 2014
Results First Received: April 17, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Biological: albiglutide
Drug: insulin glargine

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants (par.) who met eligibility criteria and completed a 4 week Run-in/Stabilization Period were then randomized to a 156-week Treatment Period, followed by 8 weeks of post-treatment follow-up. A total of 1060 par. were screened; 779 par. were randomized, and 745 par. received >=1 treatment dose.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Participant Flow for 2 periods

Period 1:   Treatment Period (156 Weeks)
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
STARTED     504     241  
COMPLETED     308     164  
NOT COMPLETED     196     77  
Adverse Event                 50                 11  
Protocol Violation                 12                 3  
Noncompliance                 21                 14  
Severe or Repeated Hypoglycaemia                 1                 0  
Lost to Follow-up                 19                 18  
Withdrawal by Subject                 81                 29  
Physician Decision                 6                 1  
Termination of Study/Site by GSK                 1                 0  
Missing                 3                 1  
Pregnancy                 2                 0  

Period 2:   Follow-up Period (8 Weeks)
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
STARTED     504 [1]   241 [1]
COMPLETED     408     190  
NOT COMPLETED     96     51  
Adverse Event                 10                 5  
Noncompliance                 6                 5  
Lost to Follow-up                 38                 22  
Did not Enter Follow-up Period                 7                 7  
Withdrawn from Follow-up Participation                 26                 12  
Physician Decision                 2                 0  
Termination of Study/Site by GSK                 2                 0  
Withdrawal by Subject                 2                 0  
Missing                 3                 0  
[1] Participants withdrawing from the Treatment Period entered the Follow-up Period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Total Total of all reporting groups

Baseline Measures
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea     Total  
Number of Participants  
[units: participants]
  504     241     745  
Age  
[units: Years]
Mean ± Standard Deviation
  55.8  ± 9.33     54.7  ± 9.75     55.5  ± 9.48  
Gender  
[units: Participants]
     
Female     218     109     327  
Male     286     132     418  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     130     64     194  
American Indian or Alaskan Native     3     1     4  
Asian - Central/South Asian Heritage     7     5     12  
Asian - East Asian Heritage     2     1     3  
Asian - Japanese Heritage     0     1     1  
Asian - South East Asian Heritage     16     8     24  
Native Hawaiian or Other Pacific Islander     1     0     1  
White - Arabic/North African Heritage     7     2     9  
White - White/Caucasian/European Heritage     342     158     500  
Other - Central American Indian     1     0     1  
Other - Hispanic     0     1     1  
Other - Mexican     1     0     1  



  Outcome Measures
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1.  Primary:   Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52   [ Time Frame: Baseline and Week 52 ]

Measure Type Primary
Measure Title Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52
Measure Description HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The BL HbA1c value is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 52 minus the value at BL. Based on analysis of covariance (ANCOVA): change = treatment + BL HbA1c + prior myocardial infarction history + age category + region + current antidiabetic therapy. Difference of least squares means (albiglutide – insulin glargine) is from the ANCOVA model. The last observation carried forward (LOCF) method was used to impute missing post-Baseline HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values.
Time Frame Baseline and Week 52  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population with LOCF: all randomized par. who received >=1 dose of study medication and who had a BL assessment and >=1 post-BL assessment of HbA1c. Only par. with a value at BL and at the specified visit were analyzed. Values were carried forward for par. who were rescued or discontinued from active treatment before Week 52.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  493     238  
Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52  
[units: Percentage of HbA1c in the blood]
Least Squares Mean ± Standard Error
  -0.67  ± 0.044     -0.79  ± 0.064  


Statistical Analysis 1 for Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52
Groups [1] All groups
Method [2] ANCOVA
Mean Difference (Net) [3] 0.11
95% Confidence Interval ( -0.04 to 0.27 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] 0.0086
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  To test whether the difference of least square means (albiglutide - insulin glargine) is equal to the pre-specified non-inferiority margin of 0.3%
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for non-inferiority testing of albiglutide versus insulin glargine

Statistical Analysis 3 for Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] 0.1463
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The p-value is from a two-sided t-test to test whether the difference of least square means (albiglutide – insulin glargine) is equal to zero.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value is for superiority testing of albiglutide versus insulin glargine



2.  Secondary:   Change From Baseline in HbA1c at Week 156   [ Time Frame: Baseline and Week 156 ]

Measure Type Secondary
Measure Title Change From Baseline in HbA1c at Week 156
Measure Description HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.
Time Frame Baseline and Week 156  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population with observed values. Only those par. with a value at Baseline and at the specified visit were analyzed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  123     88  
Change From Baseline in HbA1c at Week 156  
[units: Percentage of HbA1c in the blood]
Mean ± Standard Deviation
  -0.83  ± 0.980     -1.00  ± 0.922  

No statistical analysis provided for Change From Baseline in HbA1c at Week 156



3.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52   [ Time Frame: Baseline and Week 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52
Measure Description The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline FPG + Baseline HbA1c category + prior myocardial infarction history + age category + region + current antidiabetic therapy.
Time Frame Baseline and Week 52  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  494     238  
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52  
[units: Millimoles per liter (mmol/L)]
Least Squares Mean ± Standard Error
  -0.87  ± 0.127     -2.06  ± 0.184  

No statistical analysis provided for Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52



4.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156   [ Time Frame: Baseline and Week 156 ]

Measure Type Secondary
Measure Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156
Measure Description The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline and Week 156  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population with observed values. Only those par. with a value at Baseline and at the specified visit were analyzed. This analysis used observed FPG values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  119     86  
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156  
[units: Millimoles per liter (mmol/L)]
Mean ± Standard Deviation
  -0.83  ± 2.803     -2.19  ± 3.420  

No statistical analysis provided for Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156



5.  Secondary:   Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52   [ Time Frame: Week 52 ]

Measure Type Secondary
Measure Title Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52
Measure Description The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 52) were assessed.
Time Frame Week 52  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  493     238  
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52  
[units: Participants]
   
HbA1c <6.5%     54     25  
HbA1c <7%     156     78  
HbA1c <7.5%     268     135  

No statistical analysis provided for Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52



6.  Secondary:   Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156   [ Time Frame: Week 156 ]

Measure Type Secondary
Measure Title Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156
Measure Description The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 156) were assessed.
Time Frame Week 156  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population with observed values. Only those par. with a value at Baseline and at the specified visit were analyzed. This analysis used observed HbA1c values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  123     88  
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156  
[units: Participants]
   
HbA1c <6.5%     33     18  
HbA1c <7%     59     46  
HbA1c <7.5%     85     71  

No statistical analysis provided for Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156



7.  Secondary:   Time to Hyperglycemia Rescue   [ Time Frame: From the start of study medication until the end of the treatment (up to Week 156) ]

Measure Type Secondary
Measure Title Time to Hyperglycemia Rescue
Measure Description Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: FPG >=280 milligrams/deciliter (mg/dL) between >=Week 2 and <Week 4; FPG >=250 mg/dL between >=Week 4 and <Week 12; HbA1c >=8.5% and a <=0.5% reduction from Baseline between >=Week 12 and <Week 24; HbA1c >=8.5% between >=Week 24 and <Week 48; HbA1c >=8.0% between >= Week 48 and <Week 156. Participants could have been rescued at any time on or after Week 2. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus 1 day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus 1 day for participants not requiring rescue. This time was divided by 7 to express the result in weeks.
Time Frame From the start of study medication until the end of the treatment (up to Week 156)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Only those participants with a value at Baseline and at the specified visit were analyzed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  496     239  
Time to Hyperglycemia Rescue  
[units: Weeks]
Median ( 95% Confidence Interval )
  107.57  
  ( 96.43 to 143.43 )  
  NA  
  ( NA to NA ) [1]
[1] There were too few events of hyperglycemia rescue (<50% of participants with events) to calculate the median and confidence interval.

No statistical analysis provided for Time to Hyperglycemia Rescue



8.  Secondary:   Change From Baseline in Body Weight at Week 52   [ Time Frame: Baseline and Week 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Body Weight at Week 52
Measure Description The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region + current antidiabetic therapy.
Time Frame Baseline and Week 52  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  495     238  
Change From Baseline in Body Weight at Week 52  
[units: Kilograms]
Least Squares Mean ± Standard Error
  -1.05  ± 0.171     1.56  ± 0.247  

No statistical analysis provided for Change From Baseline in Body Weight at Week 52



9.  Secondary:   Change From Baseline in Body Weight at Week 156   [ Time Frame: Baseline and Week 156 ]

Measure Type Secondary
Measure Title Change From Baseline in Body Weight at Week 156
Measure Description The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight.
Time Frame Baseline and Week 156  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population with observed values. Only those participants who were available at the indicated time points were analyzed. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  122     89  
Change From Baseline in Body Weight at Week 156  
[units: Kilograms]
Mean ± Standard Deviation
  -3.47  ± 6.300     0.90  ± 4.890  

No statistical analysis provided for Change From Baseline in Body Weight at Week 156



10.  Secondary:   Change From Baseline in Glucose Profile Measured by 24-hour Area Under Curve (AUC) at Week 52   [ Time Frame: Baseline and Week 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Glucose Profile Measured by 24-hour Area Under Curve (AUC) at Week 52
Measure Description A 24-hour glucose profile was collected at Baseline and Week 52 at a subset of sites in a subset of participants per treatment group using the continuous glucose monitoring device. Glucose measurements were obtained at 5 minute increments in the 24-hour period. The area under the curve (AUC) was determined using the trapezoidal method on the measurements obtained during the first 24 hours of continuous monitoring. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. The Baseline value is the last non-missing value before the start of treatment.
Time Frame Baseline and Week 52  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Glucose Profile Substudy Population: all participants who participated in the 24-hour glucose profile substudy . Only those participants with a value at Baseline and Week 52 were analyzed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Insulin Glargine 10 Units + Metformin +/- Sulfonylurea Participants received 10 units of insulin glargine daily (with dose adjusted weekly depending on the need for additional glycemic control) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea     Insulin Glargine 10 Units + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  13     9  
Change From Baseline in Glucose Profile Measured by 24-hour Area Under Curve (AUC) at Week 52  
[units: Millimoles per hour per liter (mmol.h/L)]
Mean ± Standard Deviation
  0.457  ± 2.9898     -1.657  ± 1.9453  

No statistical analysis provided for Change From Baseline in Glucose Profile Measured by 24-hour Area Under Curve (AUC) at Week 52



11.  Secondary:   Albiglutide Plasma Concentrations at Week 8 and Week 24   [ Time Frame: Weeks 8 and 24 ]

Measure Type Secondary
Measure Title Albiglutide Plasma Concentrations at Week 8 and Week 24
Measure Description Albiglutide plasma concentration data was analyzed at Week 8 pre-dose, Week 8 post-dose, Week 24 pre-dose and Week 24 post-dose. All participants receiving albiglutide were initiated on a 30 mg weekly dosing regimen; however, beginning at Week 4, uptitration of albiglutide was allowed based on glycemic response. As such, albiglutide plasma concentrations achieved at each sampling time represent a mixed population of participants receiving either 30 mg or 50 mg weekly for various durations.
Time Frame Weeks 8 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Only those participants with a PK sample available for analysis at the indicated time points were analyzed.

Reporting Groups
  Description
Albiglutide 30 mg + Metformin +/- Sulfonylurea Participants received albiglutide 30 milligrams (mg) weekly (with up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin >=1500 mg daily plus or minus sulfonylurea from Baseline to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.

Measured Values
    Albiglutide 30 mg + Metformin +/- Sulfonylurea  
Number of Participants Analyzed  
[units: participants]
  459  
Albiglutide Plasma Concentrations at Week 8 and Week 24  
[units: nanograms/milliliter (ng/mL)]
Mean ± Standard Deviation
 
Week 8, Pre-dose, n=408     1642.83  ± 892.570  
Week 8, Post-dose, n=398     1911.35  ± 966.180  
Week 24, Pre-dose, n=416     2159.30  ± 1211.714  
Week 24, Post-dose, n=401     2748.15  ± 1503.945  

No statistical analysis provided for Albiglutide Plasma Concentrations at Week 8 and Week 24




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00838916     History of Changes
Other Study ID Numbers: 112754
Study First Received: February 5, 2009
Results First Received: April 17, 2014
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration