Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants | RxWiki

Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants

Overview[ - collapse ][ - ]

Purpose	To demonstrate the bioequivalence of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet to that of 2.5-mg saxagliptin (Onglyza) and 500-mg metformin (Glucophage, marketed in Canada by Sanofi-Aventis) tablets coadministered to healthy participants in the fasted and fed states.
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state) Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state) Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state) Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)
Phase	Phase 1
Sponsor	Bristol-Myers Squibb
Responsible Party	Bristol-Myers Squibb
ClinicalTrials.gov Identifier	NCT01068717
First Received	February 12, 2010
Last Updated	November 1, 2011
Last verified	November 2011

Tracking Information[ + expand ][ + ]

First Received Date	February 12, 2010
Last Updated Date	November 1, 2011
Start Date	March 2010
Estimated Primary Completion Date	March 2010
Current Primary Outcome Measures	Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No] Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No] Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: Yes] Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No] AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No] AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No] AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No] Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States [Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4] [Designated as safety issue: No]
Current Secondary Outcome Measures	Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation [Time Frame: Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4] [Designated as safety issue: Yes]An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results [Time Frame: At screening visit, at Day -1 of Periods 1 through 4, and at discharge] [Designated as safety issue: Yes]Clinically significant was determined by the investigator. Hematology tests included hemoglobin, hematocrit, red blood cell count, total leukocyte count (including differential), and platelet count. Serum chemistry tests included aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, fasting glucose, total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, and creatine kinase. Urinalysis included protein, glucose, blood, leukocyte esterase, specific gravity, and pH. Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results [Time Frame: At screening visit, Day -1 of Period 1, and at study discharge] [Designated as safety issue: Yes]Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes. Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate [Time Frame: At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge.] [Designated as safety issue: Yes]Clinically significant was determined by the investigator. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes.

Descriptive Information[ + expand ][ + ]

Brief Title	Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants
Official Title	Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 500 mg Metformin Tablet Relative to a 2.5 mg Saxagliptin (Onglyza) Tablet and a 500 mg Metformin (Glucophage Marketed in Canada by Sanofi-Aventis) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States
Brief Summary	To demonstrate the bioequivalence of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet to that of 2.5-mg saxagliptin (Onglyza) and 500-mg metformin (Glucophage, marketed in Canada by Sanofi-Aventis) tablets coadministered to healthy participants in the fasted and fed states.
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, 2.5 mg + Metformin, 500 mg (fasted state) Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week Other Names: Onglyza™ Glucophage™ Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state) Tablets, oral, 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC), once daily, 1 week Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state) Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week Other Names: Onglyza™ Glucophage™ Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state) Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin FDC, once daily, 1 week
Study Arm (s)	Other: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state) Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fasted state Other: Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fasted state) Single oral dose of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet administered in the fasted state Other: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state) Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fed state Other: Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fed state) Single oral dose of saxagliptin, 2.5 mg/metformin, 500 mg, FDC tablet administered in the fed state

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	27
Estimated Completion Date	March 2010
Estimated Primary Completion Date	March 2010
Eligibility Criteria	Inclusion Criteria: - Men and women, aged 18 to 55 years, inclusive - Healthy participants as determined by a lack of clinically significant deviation from normal in medical history, physical examination, electrocardiograms, and clinical laboratory determinations - Body Mass Index of 18 to 32 kg/m^2, inclusive 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 DPP-4 inhibitors or related compounds - History of allergy or intolerance to metformin or other similar acting agents - Previous exposure to saxagliptin - Exposure to metformin within 3 months pervious to study drug administration - Estimated creatinine clearance 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	NCT01068717
Other Study ID Numbers	CV181-118
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	November 2011

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