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 | RxWiki

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

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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	Type 2 Diabetes Mellitus
Intervention	Drug: saxagliptin Drug: metformin Drug: saxagliptin + metformin (FDC tablet)
Phase	Phase 1
Sponsor	Bristol-Myers Squibb
Responsible Party	Bristol-Myers Squibb
ClinicalTrials.gov Identifier	NCT01068743
First Received	February 12, 2010
Last Updated	January 9, 2012
Last verified	January 2012

Tracking Information[ + expand ][ + ]

First Received Date	February 12, 2010
Last Updated Date	January 9, 2012
Start Date	February 2010
Estimated Primary Completion Date	March 2010
Current 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.
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	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
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
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 1
Study Design	Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: saxagliptin Tablets, Oral, 2.5 mg, once daily, single dose Other Names: OnglyzaDrug: metformin Tablets, Oral, 850 mg, once daily, single dose Other Names: GlucophageDrug: saxagliptin + metformin (FDC tablet) Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose
Study Arm (s)	Other: 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. Other: 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. Other: 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. Other: 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.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	24
Estimated Completion Date	March 2010
Estimated Primary Completion Date	March 2010
Eligibility 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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01068743
Other Study ID Numbers	CV181-121
Has Data Monitoring Committee	No
Information Provided By	Bristol-Myers Squibb
Study Sponsor	Bristol-Myers Squibb
Collaborators	AstraZeneca
Investigators	Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Verification Date	January 2012

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