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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
5 mg saxagliptin + a single 500 mg metformin XR tablet
Intervention: saxagliptin (Drug)
5 mg saxagliptin + a single 500 mg metformin XR tablet
Intervention: metformin XR (Drug)
FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)
under fed state
Intervention: saxagliptin + metformin XR (FDC tablet) (Drug)
FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting)
under fasted state
Intervention: saxagliptin + metformin XR (FDC tablet) (Drug)
Outcomes
Primary Outcomes
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)
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)
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)
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)
Secondary Outcomes
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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 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 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))
- 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))
- 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))
- 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))
- 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.)
- 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))