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: November 7, 2013
Last verified: November 2013
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 ]

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 ]
  Hide Outcome Measure 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:
  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.



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


  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.


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
No text entered.  


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: November 7, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada