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Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin/1000 mg Metformin XR (Manufactured in Mt Vernon, IN) Relative to 5 mg of Onglyza and 2 × 500 mg Glucophage XR

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01192152
First received: August 30, 2010
Last updated: April 19, 2011
Last verified: April 2011
History of Changes
  Purpose

The purpose of this study is to demonstrate bioequivalence (BE) of a 5 mg saxagliptin/1000 mg metformin extended release (XR) fixed-dose combination (FDC) tablet (manufactured in Mt Vernon, Indiana) relative to a coadministered 5 mg Onglyza tablet (saxagliptin, manufactured in Mt Vernon, Indiana) and two 500 mg Glucophage XR tablets (metformin XR, manufactured in Evansville, Indiana) in the fed state in healthy subjects.


Condition Intervention Phase
Diabetes Mellitus
 Drug: saxagliptin
Drug: Glucophage 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/1000 mg Metformin XR (Manufactured in Mt Vernon, IN) Relative to 5 mg of Onglyza and 2 × 500 mg Glucophage XR Coadministered to Healthy Subjects in the Fed State and Steady State Pharmacokinetic Assessment of the Fixed Dose Combination of 5 mg Saxagliptin/1000 mg Metformin XR

Resource links provided by NLM:

MedlinePlus related topics: Diabetes
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

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 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing. ] [ Designated as safety issue: No ]
  • Saxagliptin Observed Maximum Plasma Concentration (Cmax) [ Time Frame: Periods 1 & 2: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 & 48 hrs post-dosing. Period 3: predosing on Days 2 & 3; predosing, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hrs postdosing on Day 4 ] [ Designated as safety issue: No ]
  • Metformin AUC(0-inf) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • Metformin Cmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing. ] [ Designated as safety issue: No ]
  • Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau]) [ Time Frame: Period 3: pre-dosing on Days 2 and 3; pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours post-dosing on Day 4. ] [ Designated as safety issue: No ]
    Dosing interval = 24 hours.

  • Saxagliptin Trough (Predose) Plasma Concentration (Cmin) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Saxagliptin Terminal Half-life (T1/2) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ 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 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax) [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin AUC(0-inf) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin AUC(0-t) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin AUC(0-tau) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin Cmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin Cmin [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin Cavg [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin Fluctuation % [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin T1/2 [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • 5-hydroxy Saxagliptin Tmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ] [ Designated as safety issue: No ]
  • Metformin AUC(0-t) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • Metformin AUC(0-tau) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Metformin Cmin [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Metformin Cavg [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Metformin Fluctuation % [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ] [ Designated as safety issue: No ]
  • Metformin T1/2 [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf]) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ] [ Designated as safety issue: No ]
  • Metformin Tmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ] [ 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 morning of Day 1/Period 1 through study discharge. 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/or 12-Lead Electrocardiogram (ECG) Abnormalities [ Time Frame: From Day 1 of Period 1 to Day 3 of Period 2 for participants in Treatment Sequence BA and Day 5 of Period 3 for participants in Treatment Sequence ABC ] [ Designated as safety issue: Yes ]
    Abnormalities considered clinically significant and/or reported as an AE by the investigator.


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 + 2 Glucophage XR 500 mg tablet Drug: saxagliptin
Tablets, Oral, 5 mg, once daily, Single dose
Other Name: Onglyza
Drug: Glucophage XR
Tablets, Oral, 500 mg, once daily, Single dose
Experimental: FDC tablet (5 mg saxa + 1000 mg metformin XR) (single dose)
under fed state, single dose
 Drug: saxagliptin + metformin XR (FDC tablet)
Tablet, Oral, (saxagliptin 5 mg)(metformin XR 1000 mg), once daily, 4 days
Other Name: Onglyza
Experimental: FDC tablet (5 mg saxa + 1000 mg metformin XR) (4 days)
under fed state, 4 days
 Drug: saxagliptin + metformin XR (FDC tablet)
Tablet, Oral, (saxagliptin 5 mg)(metformin XR 1000 mg), once daily, 4 days
Other Name: Onglyza

Detailed Description:

This study is designed to evaluate if the FDC tablet of 5 mg saxagliptin/1000 mg metformin extended release (manufactured in Mt Vernon, Indiana) is bioequivalent to the coadministered 5 mg saxagliptin tablet plus 2 x 500 mg Glucophage XR tablets (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, ECGs, and clinical laboratory determinations
  • Body Mass Index (BMI) of 18 to 32 kg/m², inclusive
  • Ages 18 to 55, 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 HIV, HBV or 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01192152

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

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01192152     History of Changes
Other Study ID Numbers: CV181-112
Study First Received: August 30, 2010
Results First Received: March 9, 2011
Last Updated: April 19, 2011
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
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013