A Study to Examine the Pharmacokinetics, Tolerability, Safety and Efficacy of Exenatide Once Weekly Suspension

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00894322
First received: May 5, 2009
Last updated: April 16, 2014
Last verified: April 2014
Results First Received: April 16, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Subject);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: exenatide once weekly
Other: Placebo

  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
Healthy participants were enrolled in Cohort 1 while participants with type 2 diabetes mellitus were enrolled in Cohort 2.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled participants in Cohort 1 were treated on Day 1 only. Enrolled participants who were in Cohort 2 were randomized to one of 2 treatment arms (exenatide or placebo) and were treated for 12 weeks.

Reporting Groups
  Description
Cohort 1 Exenatide 10 mg A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
Cohort 2 Exenatide 2 mg On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of 2 mg exenatide suspension for 12 weeks. Study medication was administered weekly.
Cohort 2 Placebo On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).

Participant Flow:   Overall Study
    Cohort 1 Exenatide 10 mg     Cohort 2 Exenatide 2 mg     Cohort 2 Placebo  
STARTED     30     23     12  
COMPLETED     29     23     12  
NOT COMPLETED     1     0     0  
Withdrawal by Subject                 1                 0                 0  



  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.
Intent to treat (ITT) population. All randomized participants who received at least 1 dose of study medication were included in the ITT population. Totals presented are for only Cohort 2 (35 participants), not for both Cohort 1 and 2.

Reporting Groups
  Description
Cohort 1 Exenatide 10 mg A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
Cohort 2 Exenatide 2 mg On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of 2 mg exenatide suspension for 12 weeks. Study medication was administered weekly.
Cohort 2 Placebo On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
Total Total of all reporting groups

Baseline Measures
    Cohort 1 Exenatide 10 mg     Cohort 2 Exenatide 2 mg     Cohort 2 Placebo     Total  
Number of Participants  
[units: participants]
  30     23     12     65  
Age  
[units: years]
Mean ± Standard Deviation
  41.2  ± 14.4     52.7  ± 11.6     52.0  ± 9.3     52.4  ± 10.7  
Gender  
[units: participants]
       
Female     12     9     2     23  
Male     18     14     10     42  
Race/Ethnicity, Customized  
[units: participants]
       
Caucasian     23     19     11     53  
Black     3     1     0     4  
Asian     0     0     1     1  
Native American     1     1     0     2  
Hispanic     3     2     0     5  
Region of Enrollment  
[units: participants]
       
United States     30     23     12     65  
Body Weight  
[units: kilograms]
Mean ± Standard Deviation
  85.9  ± 15.5     104.9  ± 23.2     104.4  ± 20.3     104.7  ± 22.0  
Body Mass Index (BMI) [1]
[units: kg/m^2]
Mean ± Standard Deviation
  28.5  ± 3.5     35.3  ± 6.7     34.9  ± 4.9     35.1  ± 6.1  
[1] BMI was measured in kilograms (kg) of body weight per meter (m) of height, squared.



  Outcome Measures
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1.  Primary:   Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population   [ Time Frame: Day 1, Week 12 ]

2.  Primary:   Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population   [ Time Frame: Day 1, Week 12 ]

3.  Primary:   Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population   [ Time Frame: Day 1, Week 12 ]

4.  Primary:   Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population   [ Time Frame: Day 1 to Week12 ]

5.  Primary:   Number of Participants With Concomitant Medications in Cohort 1 and Cohort 2 in ITT Population   [ Time Frame: Day 1 to 12 weeks ]

6.  Primary:   Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population   [ Time Frame: Day 1 to Week 12 ]

7.  Primary:   Mean Change From Baseline to End of Study in Sitting Heart Rate in Cohorts 1 and 2 in ITT Population   [ Time Frame: Day 1 to Week 12 ]

8.  Primary:   Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population   [ Time Frame: Day 1 to Week 12 ]

9.  Primary:   Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2   [ Time Frame: Day 1 to Week 12 ]

10.  Primary:   Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population   [ Time Frame: Week 10-11; Weeks 10 - 12 ]

11.  Primary:   Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population   [ Time Frame: Week 10 - Week 11; Week 10 - Week 12 ]

12.  Primary:   Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population   [ Time Frame: Week 10, Weeks 10-11, Weeks 10-12 ]

13.  Primary:   Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population   [ Time Frame: Week 10, Weeks 10-11, Weeks 10-12 ]

14.  Secondary:   AUC (0 Hour to 168 Hour) for 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population   [ Time Frame: Day 1 to Week 1 ]

15.  Secondary:   Average Exenatide Concentration (Cave) of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population   [ Time Frame: Day 1 to Week 1 ]

16.  Secondary:   Least Square Mean Change From Baseline in Hemoglobin A1c (HbA1c) to Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population   [ Time Frame: Day 1 to Week 12 ]

17.  Secondary:   Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population   [ Time Frame: Week 12 ]

18.  Secondary:   Mean Change From Baseline at Week 12 in Body Weight in Participants With Diabetes (Cohort 2) in the ITT Population   [ Time Frame: Baseline, Week 12 ]

19.  Secondary:   Mean Change From Baseline at Week 12 in Fasting Plasma Glucose in Participants With Diabetes (Cohort 2) for the ITT Population   [ Time Frame: Baseline, Week 12 ]


  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 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: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00894322     History of Changes
Other Study ID Numbers: BCB110
Study First Received: May 5, 2009
Results First Received: April 16, 2014
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration