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Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01068717
First received: February 12, 2010
Last updated: June 4, 2014
Last verified: June 2014
Results First Received: August 10, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Bio-equivalence Study;   Intervention Model: Crossover Assignment;   Masking: Open Label
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state)
Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)
Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)

  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
A total of 27 participants were enrolled and randomly assigned to 1 of 4 treatment sequences: ADBC, BACD, CBDA, or DCAB. One participant withdrew from the study on Day –1 of Period 2 due to a family emergency and returned for early termination assessments on Day 4 of Period 2. She did not receive study drug in Period 2.

Reporting Groups
  Description
Treatment Schedule ADBC (Treatment A) A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state.
Treatment Schedule BACD (Treatment B) A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment A) a single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state.
Treatment Schedule CBDA (Treatment C) A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the fed state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment A) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state.
Treatment Schedule DCAB (Treatment D) a single oral dose of 2.5-mg saxagliptin/500- mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state. Then, (Treatment A) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500- mg metformin FDC administered in the fasted state.

Participant Flow for 4 periods

Period 1:   Period 1: Treatment Schedule Phase 1
    Treatment Schedule ADBC     Treatment Schedule BACD     Treatment Schedule CBDA     Treatment Schedule DCAB  
STARTED     7     6     7     7  
COMPLETED     6 [1]   6     7     7  
NOT COMPLETED     1     0     0     0  
Patient withdrew; returned for period 3                 1                 0                 0                 0  
[1] Patient who withdrew returned for Treatment Periods 3 and 4.

Period 2:   Period 2: Treatment Schedule Phase 2
    Treatment Schedule ADBC     Treatment Schedule BACD     Treatment Schedule CBDA     Treatment Schedule DCAB  
STARTED     6     6     7     7  
COMPLETED     6     6     7     7  
NOT COMPLETED     0     0     0     0  

Period 3:   Period 3: Treatment Schedule Phase 3
    Treatment Schedule ADBC     Treatment Schedule BACD     Treatment Schedule CBDA     Treatment Schedule DCAB  
STARTED     7 [1]   6     7     7  
COMPLETED     7     6     7     7  
NOT COMPLETED     0     0     0     0  
[1] Patient who withdrew during Treatment Period 1 returned for Treatment Periods 3 and 4.

Period 4:   Period 4: Treatment Schedule Phase 4
    Treatment Schedule ADBC     Treatment Schedule BACD     Treatment Schedule CBDA     Treatment Schedule DCAB  
STARTED     7 [1]   6     7     7  
COMPLETED     7     6     7     7  
NOT COMPLETED     0     0     0     0  
[1] Patient who withdrew during Treatment Period 1 returned for Treatment Periods 3 and 4.



  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
All Treated All participants who received study medication.

Baseline Measures
    All Treated  
Number of Participants  
[units: participants]
  27  
Age, Customized  
[units: years]
Mean ± Standard Deviation
  33.6  ± 7.42  
Age, Customized  
[units: Years]
Median ( Full Range )
  32  
  ( 23 to 49 )  
Gender  
[units: participants]
 
Female     13  
Male     14  
Ethnicity (NIH/OMB)  
[units: participants]
 
Hispanic or Latino     8  
Not Hispanic or Latino     19  
Unknown or Not Reported     0  
Race/Ethnicity, Customized  
[units: Participants]
 
Black or African American     5  
White     22  



  Outcome Measures
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1.  Primary:   Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

2.  Primary:   Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

3.  Primary:   Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

4.  Primary:   Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

5.  Primary:   AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

6.  Primary:   AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

7.  Primary:   AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

8.  Primary:   Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States   [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ]

9.  Secondary:   Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation   [ Time Frame: Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4 ]

10.  Secondary:   Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results   [ Time Frame: At screening visit, at Day -1 of Periods 1 through 4, and at discharge ]

11.  Secondary:   Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results   [ Time Frame: At screening visit, Day -1 of Period 1, and at study discharge ]

12.  Secondary:   Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate   [ Time Frame: At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge. ]


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


No publications provided


Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01068717     History of Changes
Other Study ID Numbers: CV181-118
Study First Received: February 12, 2010
Results First Received: August 10, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration