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:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01068743
First received: February 12, 2010
Last updated: June 4, 2014
Last verified: June 2014
  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 AstraZeneca:

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.


Other Outcome Measures:
  • Saxagliptin PK Parameter 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.

  • Saxagliptin PK Parameter T1/2 [ 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.

  • Saxagliptin PK Parameter 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.

  • Metformin PK Parameter 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.

  • Metformin PK Parameter T1/2 [ 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.

  • Metformin PK Parameter 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.


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
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: NCT01068743

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

Responsible Party: AstraZeneca
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: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
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 September 16, 2014