Bioequivalence Study of Fixed Dose Combination of 2.5 mg Saxagliptin/850 mg Metformin Tablet Relative to 2.5 mg Onglyza and 850 mg Glucophage Tablets Co-Administered

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01068743
First received: February 12, 2010
Last updated: January 9, 2012
Last verified: January 2012
  Purpose

To demonstrate bioequivalence of a 2.5 mg saxagliptin/850 mg metformin fixed dose combination (FDC) tablet relative to the 2.5 mg saxagliptin tablet and 850 mg metformin (Glucophage Marketed by Merck-Serono) tablet co-administered to healthy subjects in the fasted and fed condition.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: saxagliptin
Drug: metformin
Drug: saxagliptin + metformin (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 2.5 mg Saxagliptin and 850 mg Metformin Tablet Relative to a 2.5 mg Saxagliptin (Onglyza) Tablet and a 850 mg Metformin (Glucophage Marketed by Merck Serono) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed Conditions

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

  • Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax) [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.

  • Metformin PK Parameter AUC(0-inf) [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

  • Metformin PK Parameter Cmax [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.


Secondary Outcome Measures:
  • 5-hydroxy Saxagliptin PK Parameter AUC(0-inf) [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

  • 5-hydroxy Saxagliptin PK Parameter Cmax [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.

  • 5-hydroxy Saxagliptin PK Parameter 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, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-t] is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.

  • 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2) [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.

  • 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) [ Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.

  • Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). [ Time Frame: AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening). ] [ 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/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    Abnormalities that were considered clinically significant and/or reported as an AE by the investigator.


Enrollment: 24
Study Start Date: February 2010
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting)
A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fasted condition.
Drug: saxagliptin
Tablets, Oral, 2.5 mg, once daily, single dose
Other Name: Onglyza
Drug: metformin
Tablets, Oral, 850 mg, once daily, single dose
Other Name: Glucophage
Arm B (saxagliptin 2.5 mg + metformin 850 mg FDC; Fasting)
A single oral dose of 2.5-mg saxagliptin/850-mg metformin fixed dose combination (FDC) administered in the fasted condition.
Drug: saxagliptin + metformin (FDC tablet)
Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose
Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)
A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fed condition.
Drug: saxagliptin
Tablets, Oral, 2.5 mg, once daily, single dose
Other Name: Onglyza
Drug: metformin
Tablets, Oral, 850 mg, once daily, single dose
Other Name: Glucophage
Arm D (saxagliptin 2.5 mg + metformin 850 mg FDC; Fed)
A single oral dose of 2.5-mg saxagliptin/850-mg metformin FDC administered in the fed condition.
Drug: saxagliptin + metformin (FDC tablet)
Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women ages 18 to 55 inclusive
  • Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
  • Body Mass Index (BMI) of 18 to 32 kg/m^2, inclusive. BMI = weight (kg)/ [height (m)]^2

Exclusion Criteria:

  • Any significant acute or chronic medical illness
  • Current or recent (within 3 months) gastrointestinal disease
  • Any major surgery within 4 weeks of study drug administration
  • History of allergy to a dipeptidyl peptidase-IV (DPP4) inhibitor or related compound
  • History of allergy or intolerance to metformin or other similar acting agents
  • Prior exposure to saxagliptin
  • Prior exposure to metformin within 3 months of study drug administration
  • Estimated creatinine clearance (Clcr) of < 80 mL/min using the Cockcroft Gault formula
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01068743

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

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01068743     History of Changes
Other Study ID Numbers: CV181-121
Study First Received: February 12, 2010
Results First Received: January 9, 2012
Last Updated: January 9, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
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 April 17, 2014