Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects With Type 2 Diabetes Mellitus(DURATION - 1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00308139
First received: March 27, 2006
Last updated: May 21, 2014
Last verified: May 2014
Results First Received: February 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Bio-availability Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: exenatide, long acting release
Drug: exenatide

  Participant Flow
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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
No text entered.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Participant Flow:   Overall Study
    Exenatide Once Weekly     Exenatide Twice Daily  
STARTED     152     151  
Intent to Treat (ITT)     148 [1]   147 [1]
ITT in the 30-Week Assessment     148 [2]   145 [2]
Pharmacokinetics Population     129     0  
Evaluable Meal Tolerance Cohort     27     24  
COMPLETED     128     130  
NOT COMPLETED     24     21  
Adverse Event                 9                 8  
Lost to Follow-up                 6                 4  
Protocol Violation                 2                 2  
Withdrawal of Consent                 6                 4  
Investigator Decision                 1                 3  
[1] Subjects who received at least one injection of lead-in exenatide 5 mcg.
[2] ITT Subjects who received at least one injection of randomized dose.



  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
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)
Total Total of all reporting groups

Baseline Measures
    Exenatide Once Weekly     Exenatide Twice Daily     Total  
Number of Participants  
[units: participants]
  148     147     295  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     122     123     245  
>=65 years     26     24     50  
Age  
[units: years]
Mean ± Standard Deviation
  55.2  ± 9.72     54.9  ± 9.63     55.0  ± 9.66  
Gender  
[units: participants]
     
Female     66     72     138  
Male     82     75     157  
Glycosylated hemoglobin (HbA1c)  
[units: percentage of total hemoglobin]
Mean ± Standard Deviation
  8.3  ± 0.99     8.3  ± 1.00     8.3  ± 0.99  
Weight  
[units: kg]
Mean ± Standard Deviation
  101.7  ± 18.76     101.9  ± 21.05     101.8  ± 19.90  
Background Oral Antidiabetic Agent  
[units: participants]
     
Diet and Exercise     21     23     44  
Metformin (MET)     56     50     106  
Sulfonylurea (SU)     6     10     16  
Thiazolidinediones (TZD)     2     7     9  
MET+SU     43     39     82  
MET+TZD     14     13     27  
SU+TZD     5     5     10  
SU+MET+TZD     1     0     1  



  Outcome Measures
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1.  Primary:   Change in HbA1c From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

Measure Type Primary
Measure Title Change in HbA1c From Baseline to Week 30
Measure Description Absolute change in HbA1c from baseline (Day -3) to Week 30 [Week 30 - Baseline]
Time Frame Day -3, Week 30  
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.
The ITT Population consisted of all randomized subjects who received at least one injection of study medication. Missing data up to Week 30 were imputed using the last observation carried forward (LOCF) approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  148     147  
Change in HbA1c From Baseline to Week 30  
[units: percentage of total hemoglobin]
Least Squares Mean ± Standard Error
  -1.87  ± 0.082     -1.54  ± 0.082  


Statistical Analysis 1 for Change in HbA1c From Baseline to Week 30
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] ANOVA
P Value [4] 0.0023
Least Squares Mean Difference [5] -0.33
Standard Error of the mean ± 0.107
95% Confidence Interval ( -0.54 to -0.12 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Superiority of exenatide long-acting release (LAR) once weekly to BYETTA if the upper limit of the 2-sided 95% confidence interval (CI) for treatment difference (LAR minus BYETTA) is less than 0; noninferiority if this upper limit is less than 0.4%. Power:Assuming 20% dropout rate with 246 subjects will complete the study. This sample size would provide 90% power for non-inferiority test with assumption of greater reduction (0.1%) in LAR and a common standard deviation of 1.2%.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  The choice of a 0.4% noninferiority margin was resulted from the considerations of expected clinical benefit of BYETTA in this study based on clinical data evaluating exenatide LAR and BYETTA, regulatory guidance, published literature, and statistical considerations.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Analysis of variance (ANOVA) model includes treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <7%   [ Time Frame: Week 30 ]

Measure Type Secondary
Measure Title Percentage of Subjects Achieving HbA1c Target of <7%
Measure Description Percentages of subjects achieving HbA1c target value of <7% at Week 30.
Time Frame Week 30  
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. Missing data up to Week 30 were imputed using LOCF for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline measurement were categorized as not achieving goal.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  148     147  
Percentage of Subjects Achieving HbA1c Target of <7%  
[units: percentage of subjects]
  70.9     51.0  


Statistical Analysis 1 for Percentage of Subjects Achieving HbA1c Target of <7%
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.0003
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Percentages of subjects achieving HbA1c target value of <7% at Week 30 were compared between treatments using a Cochran-Mantel-Haenszel (CMH) test, in which baseline HbA1c stratum (<9% or >=9%) and concomitant SU use at screening served as the stratification factors. Null hypothesis: no difference between treatments in percentage of subjects achieving HbA1c target. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <=6.5%   [ Time Frame: Week 30 ]

Measure Type Secondary
Measure Title Percentage of Subjects Achieving HbA1c Target of <=6.5%
Measure Description Percentages of subjects achieving HbA1c target values of <=6.5% at Week 30.
Time Frame Week 30  
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. Missing data up to Week 30 were imputed using LOCF for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline measurement were categorized as not achieving goal.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  148     147  
Percentage of Subjects Achieving HbA1c Target of <=6.5%  
[units: percentage of subjects]
  45.3     38.1  


Statistical Analysis 1 for Percentage of Subjects Achieving HbA1c Target of <=6.5%
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.2042
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Percentages of subjects achieving HbA1c target values of <=6.5% at Week 30 were compared between treatments using CMH test, in which baseline HbA1c stratum (<9% or >=9%) and concomitant SU use at screening served as the stratification factors. Null hypothesis: no difference between treatments in percentage of subjects achieving HbA1c target. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



4.  Secondary:   Percentage of Subjects Achieving HbA1c Target of <=6.0%   [ Time Frame: Week 30 ]

Measure Type Secondary
Measure Title Percentage of Subjects Achieving HbA1c Target of <=6.0%
Measure Description Percentages of subjects achieving HbA1c target values of <=6.0% at Week 30.
Time Frame Week 30  
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. Missing data up to Week 30 were imputed using LOCF for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline measurement were categorized as not achieving goal.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  148     147  
Percentage of Subjects Achieving HbA1c Target of <=6.0%  
[units: percentage of subjects]
  23.0     16.3  


Statistical Analysis 1 for Percentage of Subjects Achieving HbA1c Target of <=6.0%
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.1513
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Percentages of subjects achieving HbA1c target values of <=6.0% at Week 30 were compared between treatments using CMH test, in which baseline HbA1c stratum (<9% or >=9%) and concomitant SU use at screening served as the stratification factors. Null hypothesis: no difference between treatments in percentage of subjects achieving HbA1c target. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



5.  Secondary:   Change in Body Weight From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

Measure Type Secondary
Measure Title Change in Body Weight From Baseline to Week 30
Measure Description Change in body weight from baseline (Day -3) to Week 30
Time Frame Day -3, Week 30  
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. Missing data up to Week 30 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  148     147  
Change in Body Weight From Baseline to Week 30  
[units: kg]
Least Squares Mean ± Standard Error
  -3.67  ± 0.468     -3.59  ± 0.468  


Statistical Analysis 1 for Change in Body Weight From Baseline to Week 30
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.8916
Least Squares Mean Difference [4] -0.08
Standard Error of the mean ± 0.612
95% Confidence Interval ( -1.29 to 1.12 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Change in body weight from baseline (Day -3) to Week 30 was analyzed using an analysis of covariance (ANCOVA) model including treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors, and baseline value of the body weight as a covariate. Null hypothesis: no difference between treatments in change from baseline body weight. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



6.  Secondary:   Change in Fasting Plasma Glucose From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

Measure Type Secondary
Measure Title Change in Fasting Plasma Glucose From Baseline to Week 30
Measure Description Change in fasting plasma glucose from baseline (Day -3) to Week 30.
Time Frame Day -3, Week 30  
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. Missing data up to Week 30 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  148     147  
Change in Fasting Plasma Glucose From Baseline to Week 30  
[units: mg/dL]
Least Squares Mean ± Standard Error
  -41.5  ± 2.97     -24.6  ± 2.90  


Statistical Analysis 1 for Change in Fasting Plasma Glucose From Baseline to Week 30
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <.0001
Least Squares Mean Difference [4] -16.9
Standard Error of the mean ± 3.80
95% Confidence Interval ( -24.4 to -9.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Change in fasting plasma glucose from baseline (Day -3) to Week 30 was analyzed using an ANCOVA model including treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors, and baseline value of the fasting plasma glucose as a covariate. Null hypothesis: no difference between treatments in change from baseline fasting plasma glucose. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   Change in Blood Pressure From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

Measure Type Secondary
Measure Title Change in Blood Pressure From Baseline to Week 30
Measure Description Change in Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure from baseline to Week 30
Time Frame Day -3, Week 30  
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 using observed data.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  126     130  
Change in Blood Pressure From Baseline to Week 30  
[units: mmHg]
Mean ± Standard Error
   
Sitting Systolic Blood Pressure     -4.4  ± 1.04     -3.8  ± 1.28  
Sitting Diastolic Blood Pressure     -1.1  ± 0.76     -2.3  ± 0.83  

No statistical analysis provided for Change in Blood Pressure From Baseline to Week 30



8.  Secondary:   Change in Total Cholesterol From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

Measure Type Secondary
Measure Title Change in Total Cholesterol From Baseline to Week 30
Measure Description Change in total cholesterol from baseline (Day -3) to Week 30.
Time Frame Day -3, Week 30  
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. Missing data up to Week 30 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  139     137  
Change in Total Cholesterol From Baseline to Week 30  
[units: mg/dL]
Least Squares Mean ± Standard Error
  -11.9  ± 2.29     -3.8  ± 2.35  


Statistical Analysis 1 for Change in Total Cholesterol From Baseline to Week 30
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0077
Least Squares Mean Difference [4] -8.2
Standard Error of the mean ± 3.04
95% Confidence Interval ( -14.1 to -2.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Change in total cholesterol from baseline (Day -3) to Week 30 was analyzed using an ANCOVA model including treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors, and baseline value of the total cholesterol as a covariate. Null hypothesis: no difference between treatments in change from baseline total cholesterol. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



9.  Secondary:   Change in High-density Lipoprotein (HDL) From Baseline to Week 30   [ Time Frame: Day -3, Week 30 ]

Measure Type Secondary
Measure Title Change in High-density Lipoprotein (HDL) From Baseline to Week 30
Measure Description Change in high-density lipoprotein (HDL) from baseline (Day -3) to Week 30.
Time Frame Day -3, Week 30  
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. Missing data up to Week 30 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  139     137  
Change in High-density Lipoprotein (HDL) From Baseline to Week 30  
[units: mg/dL]
Least Squares Mean ± Standard Error
  -0.9  ± 0.56     -1.3  ± 0.57  


Statistical Analysis 1 for Change in High-density Lipoprotein (HDL) From Baseline to Week 30
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.5613
Least Squares Mean Difference [4] 0.4
Standard Error of the mean ± 0.74
95% Confidence Interval ( -1.0 to 1.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Change in HDL from baseline (Day -3) to Week 30 was analyzed using an ANCOVA model including treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors, and baseline value of the HDL as a covariate. Null hypothesis: no difference between treatments in change from baseline HDL. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



10.  Secondary:   Ratio of Triglycerides at Week 30 to Baseline   [ Time Frame: Day -3, Week 30 ]

Measure Type Secondary
Measure Title Ratio of Triglycerides at Week 30 to Baseline
Measure Description Ratio of triglycerides (measured in mg/dL) at Week 30 to baseline (Day -3). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Time Frame Day -3, Week 30  
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. Missing data up to Week 30 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  139     137  
Ratio of Triglycerides at Week 30 to Baseline  
[units: ratio]
Least Squares Mean ± Standard Error
  0.85  ± 0.029     0.89  ± 0.031  


Statistical Analysis 1 for Ratio of Triglycerides at Week 30 to Baseline
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.2915
Geometic Least Squares Mean Ratio [4] 0.95
Standard Error of the mean ± 0.042
95% Confidence Interval ( 0.87 to 1.04 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Triglycerides data were logarithm-transformed and the change at Week 30 to baseline (Day -3), expressed as the ratio, was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors, and baseline value of the triglycerides as a covariate. Null hypothesis: no difference between treatments in change from baseline triglycerides. Power: based on the primary measurement.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Secondary:   Exenatide LAR Steady State Concentration From Week 29 to Week 30   [ Time Frame: Week 29 to Week 30 ]

Measure Type Secondary
Measure Title Exenatide LAR Steady State Concentration From Week 29 to Week 30
Measure Description Steady-state plasma exenatide concentration over the dosing interval of Week 29 to Week 30 (0-168 hours) was evaluated. Geometric mean for the average steady-state concentration and its 10th and 90th percentiles were reported.
Time Frame Week 29 to Week 30  
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.
The Pharmacokinetics Population consisted of subjects who received exenatide LAR treatment, and had adequate plasma exenatide concentration-time data to allow for reliable evaluation of exenatide LAR pharmacokinetics.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week

Measured Values
    Exenatide Once Weekly  
Number of Participants Analyzed  
[units: participants]
  114  
Exenatide LAR Steady State Concentration From Week 29 to Week 30  
[units: pg/mL]
Geometric Mean ( Inter-Quartile Range )
  300.23  
  ( 145.13 to 702.21 )  

No statistical analysis provided for Exenatide LAR Steady State Concentration From Week 29 to Week 30



12.  Secondary:   Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events   [ Time Frame: Day 1 to Week 30 ]

Measure Type Secondary
Measure Title Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
Measure Description The major hypoglycemia category included events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject.
Time Frame Day 1 to Week 30  
Safety Issue Yes  

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 who participated in the 30-week assessment period. Analysis was done for SU ITT patients (ITT patients taking SU) and Non-SU ITT patients separately.

Reporting Groups
  Description
Exenatide Once Weekly With SU Subjects subcutaneous injection of 2 mg exenatide, once a week participating in 30-week assessment using concomitant SU at screening
Exenatide Twice Daily With SU Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) participating in 30-week assessment using concomitant SU at screening
Exenatide Once Weekly No SU Subjects subcutaneous injection of 2 mg exenatide, once a week participating in 30-week assessment not using concomitant SU at screening
Exenatide Twice Daily No SU Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) participating in 30-week assessment not using concomitant SU at screening

Measured Values
    Exenatide Once Weekly With SU     Exenatide Twice Daily With SU     Exenatide Once Weekly No SU     Exenatide Twice Daily No SU  
Number of Participants Analyzed  
[units: participants]
  55     52     93     93  
Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events  
[units: events per subject-year]
Mean ± Standard Error
  0.00  ± 0.000     0.00  ± 0.000     0.00  ± 0.000     0.00  ± 0.000  

No statistical analysis provided for Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events



13.  Secondary:   Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events   [ Time Frame: Day 1 to Week 30 ]

Measure Type Secondary
Measure Title Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events
Measure Description The minor hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Time Frame Day 1 to Week 30  
Safety Issue Yes  

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 who participated in the 30-week assessment period. Analysis was done for SU ITT patients (ITT patients taking SU) and Non-SU ITT patients separately.

Reporting Groups
  Description
Exenatide Once Weekly With SU Subjects subcutaneous injection of 2 mg exenatide, once a week participating in 30-week assessment using concomitant SU at screening
Exenatide Twice Daily With SU Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) participating in 30-week assessment using concomitant SU at screening
Exenatide Once Weekly No SU Subjects subcutaneous injection of 2 mg exenatide, once a week participating in 30-week assessment not using concomitant SU at screening
Exenatide Twice Daily No SU Subjects with subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks) participating in 30-week assessment not using concomitant SU at screening

Measured Values
    Exenatide Once Weekly With SU     Exenatide Twice Daily With SU     Exenatide Once Weekly No SU     Exenatide Twice Daily No SU  
Number of Participants Analyzed  
[units: participants]
  55     52     93     93  
Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events  
[units: events per subject-year]
Mean ± Standard Error
  0.57  ± 0.139     0.38  ± 0.113     0.00  ± 0.000     0.02  ± 0.020  

No statistical analysis provided for Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events



14.  Secondary:   Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14   [ Time Frame: Day -3, Week 14 ]

Measure Type Secondary
Measure Title Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14
Measure Description Change in 2h Postprandial Glucose from baseline (Day -3) to Week 14
Time Frame Day -3, Week 14  
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.
Evaluable Meal Tolerance Cohort consisted of ITT subjects who participated in the meal tolerance test and had adequate data to allow the reliable assessment of pharmacodynamics. Only subjects with non-missing baseline and Week 14 values were included in analysis.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week
Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 26 weeks)

Measured Values
    Exenatide Once Weekly     Exenatide Twice Daily  
Number of Participants Analyzed  
[units: participants]
  22     21  
Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14  
[units: mg/dL]
Least Squares Mean ± Standard Error
  -95.88  ± 8.420     -125.96  ± 8.292  


Statistical Analysis 1 for Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0124
Least Squares Mean Difference [4] 30.08
Standard Error of the mean ± 11.458
95% Confidence Interval ( 6.88 to 53.28 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis: Change in 2h postprandial glucose from baseline (Day -3) to Week 14 was analyzed using an ANCOVA model including treatment, baseline HbA1c stratum (<9% or >=9%), and concomitant SU use at screening as factors, and baseline value of the 2h postprandial glucose as a covariate. Null hypothesis: no difference between treatments in change from baseline 2h postprandial glucose.
[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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15.  Primary:   Sub-study Relative Bioavailability of Exenatide When Administered Using the Exenatide Once Weekly Dual Chambered Pen and the Exenatide Once Weekly Single Dose Tray (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen -11 Weekly Dose)   [ Time Frame: Week 22 ]
Results not yet posted.   Anticipated Posting Date:   02/2015   Safety Issue:   No

16.  Secondary:   Sub-study Safety and Tolerability of Exenatide When Administered Using the Once Weekly Single Dose Tray and the Once Weekly Dual (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen -11 Weekly Dose)   [ Time Frame: Week 22 ]
Results not yet posted.   Anticipated Posting Date:   02/2015   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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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