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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00308139
First received: March 27, 2006
Last updated: August 11, 2014
Last verified: August 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 ]

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

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

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

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

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

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

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

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

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

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 ]

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

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

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

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
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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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  More Information
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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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Vice President, Research and Development
Organization: Amylin Pharmaceuticals
e-mail: clinicaltrials@amylin.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00308139     History of Changes
Other Study ID Numbers: 2993LAR-105 (DURATION - 1), MB001-010
Study First Received: March 27, 2006
Results First Received: February 14, 2012
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada