Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN)

Overview[ - collapse ][ - ]

Purpose The purpose of this study is to demonstrate bioequivalence (BE) of a 5 mg saxagliptin/500 mg metformin extended release (XR) fixed-dose combination (FDC) tablet (manufactured in Mt Vernon, Indiana [IN]) to coadministered 5 mg saxagliptin and 500 mg metformin XR tablet (manufactured in Evansville, IN) in fed healthy subjects.
ConditionDiabetes Mellitus
InterventionDrug: saxagliptin
Drug: metformin XR
Drug: saxagliptin + metformin XR (FDC tablet)
PhasePhase 1
SponsorBristol-Myers Squibb
Responsible PartyBristol-Myers Squibb
ClinicalTrials.gov IdentifierNCT01192139
First ReceivedAugust 30, 2010
Last UpdatedApril 19, 2011
Last verifiedApril 2011

Tracking Information[ + expand ][ + ]

First Received DateAugust 30, 2010
Last Updated DateApril 19, 2011
Start DateNovember 2009
Estimated Primary Completion DateDecember 2009
Current Primary Outcome Measures
  • Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t [calculated using the linear trapezoidal rule] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant
  • Saxagliptin Observed Maximum Plasma Concentration (Cmax) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Metformin AUC(0-inf) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t [calculated using the linear trapezoidal rule] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant
  • Metformin Cmax [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Saxagliptin Terminal Half-life (T1/2) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]terminal half life; calculated as ln(2)/Kel
  • Saxagliptin 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, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (Ct), calculated using the linear trapezoidal rule.
  • Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf]) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Active Metabolite BMS-510849 AUC(0-inf) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t [calculated using the linear trapezoidal rule] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant
  • Active Metabolite BMS-510849 AUC(0-t) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (Ct), calculated using the linear trapezoidal rule.
  • Active Metabolite BMS-510849 Cmax [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Active Metabolite BMS-510849 T1/2 [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]terminal half life; calculated as ln(2)/Kel
  • Active Metabolite BMS-510849 Tmax [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf) [Time Frame: Period 1 (samples taken before dosing, and at 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Metformin AUC(0-t) [Time Frame: Period 1 (samples taken before dosing, and at 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)] [Designated as safety issue: No]Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (Ct), calculated using the linear trapezoidal rule.
  • Metformin T1/2 [Time Frame: Period 1 (before dosing, 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)] [Designated as safety issue: No]terminal half life; calculated as ln(2)/Kel
  • Metformin Tmax [Time Frame: Periods 1, 2, and 3 (before dosing, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf]) [Time Frame: Period 1 (before dosing, 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)] [Designated as safety issue: No]
  • Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) [Time Frame: AEs: from initiation of study drug administration on Day 1/Period 1 through study discharge Day 3/Period 3. SAEs: from date of written consent until 30 days after discontinuation of dosing or participation in study if last scheduled visit occurred later.] [Designated as safety issue: Yes]AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
  • Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities [Time Frame: From Day 1 of Period 1 through Day 3 of Period 3 (study discharge)] [Designated as safety issue: Yes]Abnormalities considered by the investigator to be clinically significant and/or reported as an AE.

Descriptive Information[ + expand ][ + ]

Brief TitleBioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN)
Official TitleBioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN) Coadministered to Healthy Subjects in a Fed Condition
Brief Summary
The purpose of this study is to demonstrate bioequivalence (BE) of a 5 mg saxagliptin/500 mg
metformin extended release (XR) fixed-dose combination (FDC) tablet (manufactured in Mt
Vernon, Indiana [IN]) to coadministered 5 mg saxagliptin and 500 mg metformin XR tablet
(manufactured in Evansville, IN) in fed healthy subjects.
Detailed Description
This study is designed to evaluate if the FDC tablet of 5 mg saxagliptin/500 mg metformin
extended release (manufactured in Mt Vernon, Indiana) is bioequivalent to the coadministered
5 mg saxagliptin and 500 mg metformin XR tablet (manufactured in Evansville, Indiana)
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label
ConditionDiabetes Mellitus
InterventionDrug: saxagliptin
Tablets, Oral, 5 mg, once daily, Single dose
Other Names:
OnglyzaDrug: metformin XR
Tablets, Oral, 500 mg. once daily, Single dose
Other Names:
Glucophage XRDrug: saxagliptin + metformin XR (FDC tablet)
Tablet, Oral, (saxagliptin 5 mg)(metformin XR 500 mg), once daily, Single dose
Study Arm (s)
  • Experimental: 5 mg saxagliptin + a single 500 mg metformin XR tablet
  • Experimental: FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)
    under fed state
  • Experimental: FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting)
    under fasted state

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment30
Estimated Completion DateDecember 2009
Estimated Primary Completion DateDecember 2009
Eligibility Criteria
Inclusion Criteria:

- Healthy male and female subjects as determined by no clinically significant deviation
from normal in medical history, physical examination, electrocardiogram (ECG), and
clinical laboratory determinations

- Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive

- Ages 18 to 45, inclusive

Exclusion Criteria:

- Evidence of organ dysfunction or any clinically significant deviation from normal in
physical examination, vital signs, ECG or clinical laboratory determinations beyond
what is consistent with the target population

- Major surgical procedure within 4 weeks prior to randomization

- Positive serology test for human immunodeficiency virus (HIV), hepatitis B virus
(HBV) or hepatitis C virus (HCV)

- Clinically significant history or presence of any of the following conditions: heart,
liver, or kidney disease, neurologic or psychiatric disease

- History of gastrointestinal disease within the past 3 months

- Any clinically significant medical condition that could potentially affect your
participation in the study and/or personal well-being, as judged by the investigator

- Donated blood or blood products to a blood bank, blood transfusion or participated in
a clinical study (except a screening visit) requiring withdrawal of blood within 4
weeks prior to randomization

- Unable to tolerate oral and/or intravenous (IV) medications

- Unable to tolerate the puncturing of veins for drawing of blood

- Known allergy or hypersensitivity to any component of the study medication

- History of any significant drug allergies (such as anaphylaxis or hepatotoxicity)

- Used any prescription drugs or over the counter products to control acid (for
example, Prevacid, Mylanta or Rolaids) within 4 weeks prior to randomization

- Used any other drugs including over the counter medications and herbal preparations
within 1 week prior to randomization

- Taken any investigational drug or placebo (inactive drug) within 4 weeks prior to
randomization
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01192139
Other Study ID NumbersCV181-111
Has Data Monitoring CommitteeNo
Information Provided ByBristol-Myers Squibb
Study SponsorBristol-Myers Squibb
CollaboratorsNot Provided
Investigators Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Verification DateApril 2011

Locations[ + expand ][ + ]

Ppd Development, Lp
Austin, Texas, United States, 78744