Bioequivalence Study of Fixed Dose Combination of 2.5 mg Saxagliptin/850 mg Metformin Tablet Relative to 2.5 mg Onglyza and 850 mg Glucophage Tablets Co-Administered

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01068743
First received: February 12, 2010
Last updated: January 9, 2012
Last verified: January 2012
Results First Received: January 9, 2012  
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
Drug: metformin
Drug: saxagliptin + metformin (FDC tablet)

  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
Participants (N = 24) who met all of the inclusion and none of the exclusion criteria were recruited from a single site in the United States.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were screened for eligibility within 21 days before Day 1 of period 1. On Day −1 of each period, the participants were admitted to the clinical facility and confined for 4 days. All the 24 participants were randomly assigned to 1 of 4 treatment sequences (ADBC, BACD, CBDA, or DCAB). The washout between each dose was at least 7 days.

Reporting Groups
  Description
Treatment Sequence ADBC Treatment A (period 1): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment D (period 2): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment B (period 3): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment C (period 4): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition.
Treatment Sequence BACD Treatment B (period 1): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment A (period 2): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment C (period 3): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment D (period 4): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition.
Treatment Sequence CBDA Treatment C (period 1): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment B (period 2): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment D (period 3): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment A (period 4): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition.
Treatment Sequence DCAB Treatment D (period 1): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment C (period 2): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment A (period 3): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment B (period 4): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition.

Participant Flow for 4 periods

Period 1:   Period 1
    Treatment Sequence ADBC     Treatment Sequence BACD     Treatment Sequence CBDA     Treatment Sequence DCAB  
STARTED     6     6     6     6  
COMPLETED     6     6     6     6  
NOT COMPLETED     0     0     0     0  

Period 2:   Period 2
    Treatment Sequence ADBC     Treatment Sequence BACD     Treatment Sequence CBDA     Treatment Sequence DCAB  
STARTED     6     6     6     6  
COMPLETED     6     6     6     6  
NOT COMPLETED     0     0     0     0  

Period 3:   Period 3
    Treatment Sequence ADBC     Treatment Sequence BACD     Treatment Sequence CBDA     Treatment Sequence DCAB  
STARTED     6     6     6     6  
COMPLETED     6     5     6     6  
NOT COMPLETED     0     1     0     0  
Adverse Event                 0                 1                 0                 0  

Period 4:   Period 4
    Treatment Sequence ADBC     Treatment Sequence BACD     Treatment Sequence CBDA     Treatment Sequence DCAB  
STARTED     6     5     6     6  
COMPLETED     6     5     6     6  
NOT COMPLETED     0     0     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.
No text entered.

Reporting Groups
  Description
All Enrolled and Treated Participants No text entered.

Baseline Measures
    All Enrolled and Treated Participants  
Number of Participants  
[units: participants]
  24  
Age  
[units: years]
Mean ± Standard Deviation
  35.5  ± 10.61  
Gender  
[units: participants]
 
Female     8  
Male     16  
Ethnicity (NIH/OMB)  
[units: participants]
 
Hispanic or Latino     11  
Not Hispanic or Latino     13  
Unknown or Not Reported     0  
Race (NIH/OMB)  
[units: participants]
 
American Indian or Alaska Native     0  
Asian     0  
Native Hawaiian or Other Pacific Islander     0  
Black or African American     3  
White     21  
More than one race     0  
Unknown or Not Reported     0  
Region of Enrollment  
[units: participants]
 
United States     24  
Height  
[units: cm]
Mean ± Standard Deviation
  170.2  ± 12.0  
Weight  
[units: kg]
Mean ± Standard Deviation
  79.7  ± 13.7  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  27.4  ± 3.05  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

2.  Primary:   Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

3.  Primary:   Metformin PK Parameter AUC(0-inf)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

4.  Primary:   Metformin PK Parameter Cmax   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

5.  Secondary:   5-hydroxy Saxagliptin PK Parameter AUC(0-inf)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

6.  Secondary:   5-hydroxy Saxagliptin PK Parameter Cmax   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

7.  Secondary:   5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

8.  Secondary:   5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

9.  Secondary:   5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

10.  Secondary:   Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs).   [ Time Frame: AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening). ]

11.  Secondary:   Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities   [ Time Frame: From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). ]

12.  Other Pre-specified:   Saxagliptin PK Parameter AUC(0-t)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

13.  Other Pre-specified:   Saxagliptin PK Parameter T1/2   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

14.  Other Pre-specified:   Saxagliptin PK Parameter Tmax   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

15.  Other Pre-specified:   Metformin PK Parameter AUC(0-t)   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

16.  Other Pre-specified:   Metformin PK Parameter T1/2   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]

17.  Other Pre-specified:   Metformin PK Parameter Tmax   [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ]


  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 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.


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


No publications provided


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01068743     History of Changes
Other Study ID Numbers: CV181-121
Study First Received: February 12, 2010
Results First Received: January 9, 2012
Last Updated: January 9, 2012
Health Authority: United States: Food and Drug Administration