To demonstrate bioequivalence of a 2.5 mg saxagliptin/500 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 500 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
24
Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions
Mds Pharma Services
Lincoln, Nebraska, United States
Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)
Cmax of single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}
AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])
AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max)
T-half and T-max for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg) or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Metformin Mean Cmax
Cmax of single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
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Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Metformin Mean AUC (0-T)
AUC (0-T for single-dose metformin (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Metformin Mean AUC(0-INF)
AUC (0-INF) for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Metformin T-half and T-max
T-half and T-max for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg), or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
BMS-510849 Mean Cmax
Cmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
BMS-510849 Mean AUC (0-T)
AUC (0-T) for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administration as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
BMS-510849 Mean AUC (0-INF)
AUC (0-T)= for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
BMS-510849 Mean T-half and T-max
T-half and Tmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administerd as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time frame: From Day 1 through Day 45, including up to 56 days after last dose of study medication
Number of Participants With Laboratory Marked Abnormalities
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Leukocytes: \<0.9 x LLN/ \>1.2 x ULN; blood urea nitrogen (BUN): \>1.1 x ULN; creatinine: \>1.33 x BL; phosphorous (P): \<0.75 x LLN/ \>1.2 5 x ULN; creatinine kinase (CK): \>1.5 x ULN; urine blood=use ≥2 x BL if value ≥2+ or BL1+
Time frame: From Day 1 through Day 45, including up to 56 days after last dose of study medication
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities
PR interval, QRS complex, width of QRS, QT interval, and QT corrected for heart rate adjusting for heart rate using either Bazett formula or Fridericia formula were measured. ECG abnormalities were judged to be of medical importance by the Investigator.
Time frame: Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3
Number of Participants With Clinically Relevant Vital Sign Abnormalities
Mean systolic and diastolic blood pressure, heart rate, respiration, and temperature were assessed.Vital sign abnormalities abnormalities were judged to be of medical importance by the Investigator.
Time frame: Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3
Number of Participant With Clinically Relevant Physical Examination Abnormalities
A physical examination was conducted which included height and weight measurements, from which the Body Mass Index was determined. Physical examination abnormalities were judged to be of medical importance by the Investigator.
Time frame: Screen, Period 1 Day -1, prior to discharge