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)

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) Coadministered to Healthy Subjects in a Fed Condition

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01192139

Enrollment

Registered

2010-08-31

Start date

2009-11-30

Completion date

2009-12-31

Last updated

2015-05-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus

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)

Interventions

DRUGsaxagliptin

Tablets, Oral, 5 mg, once daily, Single dose

DRUGmetformin XR

Tablets, Oral, 500 mg. once daily, Single dose

DRUGsaxagliptin + metformin XR (FDC tablet)

Tablet, Oral, (saxagliptin 5 mg)(metformin XR 500 mg), once daily, Single dose

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])	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)	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)	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)	—
Metformin AUC(0-inf)	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)	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	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)	—

Secondary

Measure	Time frame	Description
Active Metabolite BMS-510849 AUC(0-inf)	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)	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)	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)	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	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)	—
Active Metabolite BMS-510849 T1/2	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)	terminal half life; calculated as ln(2)/Kel
Active Metabolite BMS-510849 Tmax	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)	—
Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)	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)	—
Saxagliptin Terminal Half-life (T1/2)	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)	terminal half life; calculated as ln(2)/Kel
Metformin T1/2	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)	terminal half life; calculated as ln(2)/Kel
Metformin Tmax	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)	—
Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])	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)	—
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	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.	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	From Day 1 of Period 1 through Day 3 of Period 3 (study discharge)	Abnormalities considered by the investigator to be clinically significant and/or reported as an AE.
Metformin AUC(0-t)	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)	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.
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])	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)	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)	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)	—
Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])	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)	—

Countries

United States

Participant flow

Pre-assignment details

Participants underwent screening evaluations to determine eligibility within 21 days before dosing, and were admitted to the clinical facility the evening before dosing (Day -1). On Day 1 of Period 1, a total of 30 participants who met all of the inclusion and none of the exclusion criteria were randomly assigned to 1 of 6 treatment sequences.

Participants by arm

Arm	Count
All Enrolled and Treated Participants	30
Total	30

Baseline characteristics

Characteristic	All Enrolled and Treated Participants
Age, Continuous	29.1 years STANDARD_DEVIATION 8
Body Mass Index	26.97 kg/m^2 STANDARD_DEVIATION 3.07
Height	170.0 cm STANDARD_DEVIATION 9.22
Race/Ethnicity, Customized Asian	1 participants
Race/Ethnicity, Customized Black or African American	12 participants
Race/Ethnicity, Customized Hispanic or Latino	9 participants
Race/Ethnicity, Customized Not Hispanic or Latino	21 participants
Race/Ethnicity, Customized White	17 participants
Sex: Female, Male Female	14 Participants
Sex: Female, Male Male	16 Participants
Weight	78.31 kg STANDARD_DEVIATION 13.74

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	3 / 30	4 / 30	2 / 30
serious Total, serious adverse events	0 / 30	0 / 30	0 / 30

Outcome results

Primary

Metformin AUC(0-inf)

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

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)

Population: Treated participants (the smaller sample size for AUC\[0-inf\] was due to the inability to estimate potassium chloride for some participants)

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Metformin AUC(0-inf)	5865.92 ng*hr/mL	Standard Deviation 2357.15
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Metformin AUC(0-inf)	5516.97 ng*hr/mL	Standard Deviation 2423.08
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Metformin AUC(0-inf)	5073.70 ng*hr/mL	Standard Deviation 1406.45

Comparison: If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of a saxagliptin tablet and a metformin XR tablet under fed conditions, then 24 subjects would have provided 99% power to conclude BE with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided 96% and 97% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [0.836, 1.002]

90% CI: [0.918, 1.111]

Comparison: Geometric least squares means for treatment A

Comparison: Geometric least squares mean for treatment B

Comparison: Geometric least squares mean for treatment C

Primary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Metformin Cmax	629.73 ng/mL	Standard Deviation 160.14
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Metformin Cmax	586.87 ng/mL	Standard Deviation 150.63
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Metformin Cmax	657.23 ng/mL	Standard Deviation 187.67

Comparison: If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of a metformin XR tablet under fed conditions, then 24 subjects would have provided 99% power to conclude BE with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided 96% and 97% power to conclude BE with respect to Cmax and AUC0-inf, respectively.95% CI: [0.865, 1.007]

90% CI: [0.832, 0.969]

Comparison: Geometric least squares mean for treatment A

Comparison: Geometric least squares mean for treatment B

Comparison: Geometric least squares mean for treatment C

Primary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])	107.28 ng*hr/mL	Standard Deviation 25.13
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])	111.72 ng*hr/mL	Standard Deviation 26.55
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])	103.35 ng*hr/mL	Standard Deviation 23.15

Comparison: If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of a saxagliptin tablet and a metformin XR tablet under fed conditions, then 24 subjects would have provided 99% power to conclude bioequivalence (BE) with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided 94% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [1.011, 1.068]

90% CI: [1.049, 1.108]

Comparison: Geometric least squares means for treatment A

Comparison: Geometric least squares means for treatment B

Comparison: Geometric least squares mean for treatment C

Primary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Saxagliptin Observed Maximum Plasma Concentration (Cmax)	26.84 ng/mL	Standard Deviation 8.26
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Saxagliptin Observed Maximum Plasma Concentration (Cmax)	27.25 ng/mL	Standard Deviation 7.95
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Saxagliptin Observed Maximum Plasma Concentration (Cmax)	28.85 ng/mL	Standard Deviation 8.62

90% CI: [0.873, 1.031]

Comparison: Geometric least squares mean for treatment A

Comparison: Geometric least squares mean for treatment B

Comparison: Geometric least squares mean for treatment C

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Active Metabolite BMS-510849 AUC(0-inf)	291.72 ng*hr/mL	Standard Deviation 79.21
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Active Metabolite BMS-510849 AUC(0-inf)	295.94 ng*hr/mL	Standard Deviation 75.4
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Active Metabolite BMS-510849 AUC(0-inf)	289.06 ng*hr/mL	Standard Deviation 66.89

Secondary

Active Metabolite BMS-510849 AUC(0-t)

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 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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Active Metabolite BMS-510849 AUC(0-t)	284.46 ng*hr/mL	Standard Deviation 78.25
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Active Metabolite BMS-510849 AUC(0-t)	289.03 ng*hr/mL	Standard Deviation 74.8
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Active Metabolite BMS-510849 AUC(0-t)	281.79 ng*hr/mL	Standard Deviation 65.91

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)	0.974 ratio	Standard Deviation 0.008
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)	0.975 ratio	Standard Deviation 0.008
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)	0.974 ratio	Standard Deviation 0.006

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Active Metabolite BMS-510849 Cmax	49.71 ng/mL	Standard Deviation 16.94
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Active Metabolite BMS-510849 Cmax	49.28 ng/mL	Standard Deviation 14.59
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Active Metabolite BMS-510849 Cmax	49.09 ng/mL	Standard Deviation 15.46

Secondary

Active Metabolite BMS-510849 T1/2

terminal half life; calculated as ln(2)/Kel

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Active Metabolite BMS-510849 T1/2	13.88 hours	Standard Deviation 1.53
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Active Metabolite BMS-510849 T1/2	13.65 hours	Standard Deviation 1.72
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Active Metabolite BMS-510849 T1/2	14.04 hours	Standard Deviation 1.33

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Active Metabolite BMS-510849 Tmax	2.38 hours	Standard Deviation 0.76
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Active Metabolite BMS-510849 Tmax	2.42 hours	Standard Deviation 0.88
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Active Metabolite BMS-510849 Tmax	1.46 hours	Standard Deviation 0.7

Secondary

Metformin AUC(0-t)

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 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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Metformin AUC(0-t)	5617.39 ng*hr/mL	Standard Deviation 2181.99
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Metformin AUC(0-t)	5200.46 ng*hr/mL	Standard Deviation 2203.34
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Metformin AUC(0-t)	4896.95 ng*hr/mL	Standard Deviation 1340.41

90% CI: [0.854, 0.992]

95% CI: [0.951, 1.105]

Comparison: Geometric least squares means for treatment A

Comparison: Geometric least squares mean for treatment B

Comparison: Geometric least squares means for treatment C

Secondary

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)

Population: Treated participants (the smaller sample size for AUC(0-inf) was due to the inability to estimate Kel for some of the subjects).

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])	0.979 ratio	Standard Deviation 0.02
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])	0.970 ratio	Standard Deviation 0.026
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])	0.965 ratio	Standard Deviation 0.031

Secondary

Metformin T1/2

terminal half life; calculated as ln(2)/Kel

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)

Population: Treated participants (the smaller sample size for T1/2 was due to the inability to estimate Kel for some of the subjects).

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Metformin T1/2	10.7 hours	Standard Deviation 5.9
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Metformin T1/2	12.6 hours	Standard Deviation 7.05
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Metformin T1/2	14.9 hours	Standard Deviation 7.4

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Metformin Tmax	4.78 hours	Standard Deviation 1.04
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Metformin Tmax	4.90 hours	Standard Deviation 1.13
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Metformin Tmax	4.11 hours	Standard Deviation 0.88

Secondary

Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)

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.

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.

Population: Safety Population = all participants who received any study drug.

Arm	Measure	Group	Value (NUMBER)
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Number of Participants With At Least 1 AE	3 Participants
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Discontinuation Due to an AE	0 Participants
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Deaths	0 Participants
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	SAEs	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	SAEs	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Number of Participants With At Least 1 AE	2 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Deaths	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Discontinuation Due to an AE	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	SAEs	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Discontinuation Due to an AE	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Deaths	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)	Number of Participants With At Least 1 AE	4 Participants

Secondary

Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities

Abnormalities considered by the investigator to be clinically significant and/or reported as an AE.

Time frame: From Day 1 of Period 1 through Day 3 of Period 3 (study discharge)

Population: Safety Population

Arm	Measure	Group	Value (NUMBER)
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Clinical Laboratory Abnormalities	0 Participants
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Physical Examination Abnormalities	0 Participants
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	12-Lead ECG Abnormalities	0 Participants
Treatment A - Saxagliptin + Metformin XR, Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Vital Sign Abnormalities	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Clinical Laboratory Abnormalities	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Vital Sign Abnormalities	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Physical Examination Abnormalities	0 Participants
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	12-Lead ECG Abnormalities	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Physical Examination Abnormalities	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Clinical Laboratory Abnormalities	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	Vital Sign Abnormalities	0 Participants
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities	12-Lead ECG Abnormalities	0 Participants

Secondary

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

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 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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])	105.47 ng*hr/mL	Standard Deviation 24.98
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])	109.88 ng*hr/mL	Standard Deviation 26.36
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])	101.52 ng*hr/mL	Standard Deviation 23.01

90% CI: [1.011, 1.068]

90% CI: [1.051, 1.11]

Comparison: Geometric least squares mean for treatment A

Comparison: Geometric least squares mean for treatment B

Comparison: Geometric least squares mean for treatment C

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])	0.983 ratio	Standard Deviation 0.006
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])	0.983 ratio	Standard Deviation 0.006
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])	0.982 ratio	Standard Deviation 0.008

Secondary

Saxagliptin Terminal Half-life (T1/2)

terminal half life; calculated as ln(2)/Kel

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Saxagliptin Terminal Half-life (T1/2)	8.46 hours	Standard Deviation 2.85
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Saxagliptin Terminal Half-life (T1/2)	8.56 hours	Standard Deviation 3.04
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Saxagliptin Terminal Half-life (T1/2)	9.21 hours	Standard Deviation 3.91

Secondary

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)

Population: All treated participants

Arm	Measure	Value (MEAN)	Dispersion
Treatment A - Saxagliptin + Metformin XR, Fed	Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)	1.65 hours	Standard Deviation 0.65
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)	1.48 hours	Standard Deviation 0.75
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)	0.65 hours	Standard Deviation 0.5

Source: ClinicalTrials.gov · Data processed: Mar 30, 2026

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)

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Metformin AUC(0-inf)

Metformin Cmax

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])

Saxagliptin Observed Maximum Plasma Concentration (Cmax)

Active Metabolite BMS-510849 AUC(0-inf)

Active Metabolite BMS-510849 AUC(0-t)

Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)

Active Metabolite BMS-510849 Cmax

Active Metabolite BMS-510849 T1/2

Active Metabolite BMS-510849 Tmax

Metformin AUC(0-t)

Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])

Metformin T1/2

Metformin Tmax

Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)

Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])

Saxagliptin Terminal Half-life (T1/2)

Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)