Bioequivalence Study

Overview[ - collapse ][ - ]

Purpose The purpose of this study is to determine if tablets manufactured at different sites have the same bioavailability, that is yield similar blood levels/concentrations of the drugs and are handled by the body similarly
ConditionDiabetes
InterventionDrug: Saxagliptin/Metformin
PhasePhase 1
SponsorBristol-Myers Squibb
Responsible PartyBristol-Myers Squibb
ClinicalTrials.gov IdentifierNCT01874080
First ReceivedJune 6, 2013
Last UpdatedNovember 8, 2013
Last verifiedNovember 2013

Tracking Information[ + expand ][ + ]

First Received DateJune 6, 2013
Last Updated DateNovember 8, 2013
Start DateJune 2013
Estimated Primary Completion DateJuly 2013
Current Primary Outcome Measures
  • Point estimates and 90% CIs for the ratio of geometric means for Cmax for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]Cmax=Maximum observed plasma concentration
    CI=Confidence interval
    FDC=Fixed dosed combination
    XR=Extended release
  • Point estimates and 90% CIs for the ratio of geometric means for AUC(0-T) for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]AUC(0-T)=Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
  • Point estimates and 90% CIs for the ratio of geometric means for AUC(INF) for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]AUC(INF)=Area under the plasma concentration-time curve from time zero extrapolated to infinity
  • Point estimates and 90% CIs for the ratio of geometric means for Cmax for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • Point estimates and 90% CIs for the ratio of geometric means for AUC(0-T) for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • Point estimates and 90% CIs for the ratio of geometric means for AUC(INF) for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Time to maximum observed plasma concentration (Tmax) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • Terminal half life (T-HALF) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • Cmax for 5-OH Saxagliptin (Treatments A, B, C, and D) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • AUC(0-T) for 5-OH Saxagliptin (Treatments A, B, C, and D) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • AUC(INF) for 5-OH Saxagliptin (Treatments A, B, C, and D) [Time Frame: 19 time points up to Day 3 of Periods 1 and 2] [Designated as safety issue: No]
  • Safety assessments based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests [Time Frame: Up to Day 3 of Periods 1 and 2 and up to 30 days post discontinuation of dosing] [Designated as safety issue: Yes]Parameters will include:
    Serious adverse events
    Deaths
    Adverse events leading to discontinuation
    Number of subjects with potentially clinically significant changes in vital signs, electrocardiograms (ECGs) or safety laboratory findings defined as meeting marked abnormality criteria

Descriptive Information[ + expand ][ + ]

Brief TitleBioequivalence Study
Official TitleBioequivalence Study of the Fixed Dosed Combination of 5 mg Saxagliptin and 1000 mg Metformin Extended Release Tablet Manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico Relative to the Fixed Dosed Combination Tablet Manufactured in Mt. Vernon, Indiana and Bioequivalence Study of the Fixed Dosed Combination of 5 mg Saxagliptin and 500 mg Metformin Extended Release Tablet Manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico Relative to the Fixed Dosed Combination Tablet Manufactured in Mt. Vernon, Indiana Administered to Healthy Subjects Under Fed Conditions
Brief Summary
The purpose of this study is to determine if tablets manufactured at different sites have
the same bioavailability, that is yield similar blood levels/concentrations of the drugs and
are handled by the body similarly
Detailed Description
Primary Purpose:

Other: Protocol designed to demonstrate the bioequivalence of the fixed dose combination of
5 mg Saxagliptin and 1000 mg Metformin Extended Release Tablet manufactured in Mt. Vernon,
Indiana and Humacao, Puerto Rico relative to the fixed dose combination tablet manufactured
in Mt. Vernon, Indiana and the bioequivalence of the fixed dose combination of 5 mg
Saxagliptin and 500 mg Metformin Extended Release Tablet manufactured in Mt. Vernon, Indiana
and Humacao, Puerto Rico relative to the fixed dose combination tablet manufactured in Mt.
Vernon, Indiana in healthy human subjects under fed conditions
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label
ConditionDiabetes
InterventionDrug: Saxagliptin/Metformin
Other Names:
Kombiglyze XR
Study Arm (s)
  • Experimental: Arm A: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao)
    Saxagliptin 5 mg /Metformin 1000 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day 1 of Periods 1 and 2
  • Experimental: Arm B: Saxagliptin/Metformin XR FDC (Mt. Vernon)
    Saxagliptin 5 mg/Metformin 1000 mg (Mt. Vernon) tablet by mouth once daily on Day 1 of Periods 1 and 2
  • Experimental: Arm C: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao)
    Saxagliptin 5 mg/Metformin 500 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day1 of Periods 1 and 2
  • Experimental: Arm D: Saxagliptin/Metformin XR FDC (Mt. Vernon)
    Saxagliptin 5 mg/Metformin 500 mg (Mt. Vernon) tablet by mouth once daily Day 1 of Periods 1 and 2

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment56
Estimated Completion DateJuly 2013
Estimated Primary Completion DateJuly 2013
Eligibility Criteria
Inclusion Criteria:

- Healthy male and female subjects, 18-45 years of age

- Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive

- Women must have a negative serum or urine pregnancy test within 24 hours prior to the
start of investigational product

Exclusion Criteria:

- Any significant acute or chronic medical illness

- Estimated creatinine clearance of <60 mL/min as calculated using the Modification of
Diet in Renal Disease method Current or recent (within 3 months of study drug
administration)

- Gastrointestinal (GI) disease that could affect the absorption of study drug

- Inability to tolerate oral medication

- History of allergies or adverse reactions to DPP4 inhibitors or Metformin or related
compounds

- Current smoker or recent (within 6 months of study drug administration) history of
regular tobacco use (positive cotinine test)
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01874080
Other Study ID NumbersCV181-208
Has Data Monitoring CommitteeNo
Information Provided ByBristol-Myers Squibb
Study SponsorBristol-Myers Squibb
CollaboratorsAstraZeneca
Investigators Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Verification DateNovember 2013

Locations[ + expand ][ + ]

Icon Development Solutions
San Antonio, Texas, United States, 78209