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)

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01192139
First received: August 30, 2010
Last updated: June 4, 2014
Last verified: June 2014
  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.


Condition Intervention Phase
Diabetes Mellitus
Drug: saxagliptin
Drug: metformin XR
Drug: saxagliptin + metformin XR (FDC tablet)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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 ]

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.


Enrollment: 30
Study Start Date: November 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5 mg saxagliptin + a single 500 mg metformin XR tablet Drug: saxagliptin
Tablets, Oral, 5 mg, once daily, Single dose
Other Name: Onglyza
Drug: metformin XR
Tablets, Oral, 500 mg. once daily, Single dose
Other Name: Glucophage XR
Experimental: FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)
under fed state
Drug: saxagliptin + metformin XR (FDC tablet)
Tablet, Oral, (saxagliptin 5 mg)(metformin XR 500 mg), once daily, Single dose
Experimental: FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting)
under fasted state
Drug: saxagliptin + metformin XR (FDC tablet)
Tablet, Oral, (saxagliptin 5 mg)(metformin XR 500 mg), once daily, Single dose

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)

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01192139

Locations
United States, Texas
Ppd Development, Lp
Austin, Texas, United States, 78744
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01192139     History of Changes
Other Study ID Numbers: CV181-111
Study First Received: August 30, 2010
Results First Received: March 11, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014