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

February 12, 2010
January 9, 2012
February 2010
March 2010   (final data collection date for primary outcome measure)
  • 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.
Evidence of bioequivalence between FDC of saxagliptin and metformin with co-administrated saxagliptin and metformin (Glucophage Marketed by Merck-Serono) in the fasted and fed state in healthy subjects [ Time Frame: Within the first 24 hours of dosing ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01068743 on ClinicalTrials.gov Archive Site
  • 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.
  • To assess the pharmacokinetics of the active metabolite of saxagliptin, BMS-510849, when saxagliptin is co-administered with a metformin (Glucophage) tablet and in a FDC tablet with metformin under fasted and fed condition in healthy subjects [ Time Frame: 14 time points up to 24 hours after dosing ] [ Designated as safety issue: Yes ]
  • To assess the safety and tolerability of 2.5 mg saxagliptin when co-administered with a 850 mg metformin tablet and in a FDC tablet with metformin IR under fasted and under fed condition in healthy subjects [ Time Frame: 14 time points up to 24 hours after dosing ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Type 2 Diabetes Mellitus
  • 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
  • Drug: saxagliptin + metformin (FDC tablet)
    Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose
  • 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.
    Interventions:
    • Drug: saxagliptin
    • Drug: metformin
  • 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.
    Intervention: Drug: saxagliptin + metformin (FDC tablet)
  • 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.
    Interventions:
    • Drug: saxagliptin
    • Drug: metformin
  • 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.
    Intervention: Drug: saxagliptin + metformin (FDC tablet)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
March 2010
March 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01068743
CV181-121
No
Bristol-Myers Squibb
Bristol-Myers Squibb
AstraZeneca
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP