Type 2 Diabetes Mellitus
Conditions
Brief summary
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.
Interventions
DRUGCo-administration of Saxagliptin and Metformin IR, Fasted
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
DRUGSaxagliptin/Metformin, Fasting
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
DRUGCo-administration of Saxagliptin and Metformin IR, Fed
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
DRUGSaxagliptin/Metformin, Fed
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
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women ages 19 to 45 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/m2, inclusive. BMI = weight (kg)/ \[height (m)\]2
Exclusion criteria
* Women of child-bearing potential (WOCBP) who are unwilling or unable to use acceptable barrier methods (condoms and spermicides) to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product * 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 Dipeptidyl peptidase 4 (DPP4) inhibitor or related compounds * 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 \< 80ml/min using the Cockcroft Gault formula
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metformin Mean Cmax | 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 | 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. |
| Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) | 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 | 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. |
| Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} | 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 | 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. |
| Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) | 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 | 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. |
| Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | 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 | 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. |
| Metformin Mean AUC (0-T) | 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 | 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. |
| Metformin Mean AUC(0-INF) | 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 | 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. |
| Metformin T-half and T-max | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMS-510849 Mean Cmax | 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 | 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. |
| Number of Participant With Clinically Relevant Physical Examination Abnormalities | Screen, Period 1 Day -1, prior to discharge | 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. |
| BMS-510849 Mean AUC (0-T) | 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 | 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. |
| BMS-510849 Mean AUC (0-INF) | 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 | 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. |
| BMS-510849 Mean T-half and T-max | 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 | 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. |
| Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | From Day 1 through Day 45, including up to 56 days after last dose of study medication | 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. |
| Number of Participants With Laboratory Marked Abnormalities | From Day 1 through Day 45, including up to 56 days after last dose of study medication | 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+ |
| Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities | Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3 | 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. |
| Number of Participants With Clinically Relevant Vital Sign Abnormalities | Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3 | 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. |
Countries
United States
Participant flow
Pre-assignment details
85 participants were enrolled and 24 were treated on study. 61 participants discontinued before randomization and treatment due to: no longer meeting study criteria (n=36), withdraw of consent (n=3), study was full (n=15), participant did not call for results (n=1), completed alternate status (n=5), or did not show for check-up (n=1)
Participants by arm
| Arm | Count |
|---|---|
| All Treated Participants Participants were randomized to received 1 of 4 treatments 1)oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions, 2) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions, 3) oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions, or 4) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions. Participants received all 4 treatments in 1 of 4 sequences: 1-4-2-3, 2-1-3-4, 3-2-4-1, or 4-3-1-2, with a washout period between treatments of at least 1 week. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Treated Participants |
|---|---|
| Age, Continuous | 28 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 3 / 24 | 4 / 24 | 1 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Metformin Mean AUC(0-INF) | 7494.67 ng*h/mL | Standard Deviation 1792.921 |
| Saxagliptin/Metformin FDC (Fasted) | Metformin Mean AUC(0-INF) | 7689.57 ng*h/mL | Standard Deviation 1761.119 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Metformin Mean AUC(0-INF) | 7246.89 ng*h/mL | Standard Deviation 1215.675 |
| Saxagliptin/Metformin FDC (Fed) | Metformin Mean AUC(0-INF) | 7574.17 ng*h/mL | Standard Deviation 1397.335 |
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log\[AUC(INF)\] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.973, 1.088]Mixed Models Analysis
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log\[AUC(INF)\] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.986, 1.102]Mixed Models Analysis
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Metformin Mean AUC (0-T) | 7403.01 ng*h/mL | Standard Deviation 1822.749 |
| Saxagliptin/Metformin FDC (Fasted) | Metformin Mean AUC (0-T) | 7575.23 ng*h/mL | Standard Deviation 1832.807 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Metformin Mean AUC (0-T) | 7176.78 ng*h/mL | Standard Deviation 1216.854 |
| Saxagliptin/Metformin FDC (Fed) | Metformin Mean AUC (0-T) | 7502.46 ng*h/mL | Standard Deviation 1402.256 |
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log\[AUC(0-T)\] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.964, 1.088]Mixed Models Analysis
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log\[AUC(0-T)\] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.981, 1.108]Mixed Models Analysis
Primary
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.
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Metformin Mean Cmax | 1030.22 ng/mL | Standard Deviation 293.97 |
| Saxagliptin/Metformin FDC (Fasted) | Metformin Mean Cmax | 1042.52 ng/mL | Standard Deviation 314.365 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Metformin Mean Cmax | 993.32 ng/mL | Standard Deviation 198.653 |
| Saxagliptin/Metformin FDC (Fed) | Metformin Mean Cmax | 1027.70 ng/mL | Standard Deviation 208.974 |
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log(Cmax) of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.939, 1.084]Mixed Models Analysis
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log(Cmax) of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.962, 1.111]Mixed Models Analysis
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Metformin T-half and T-max | T-Half | 9.87 hours | Standard Deviation 5.561 |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Metformin T-half and T-max | T-max | 3.18 hours | Standard Deviation 0.919 |
| Saxagliptin/Metformin FDC (Fasted) | Metformin T-half and T-max | T-Half | 12.03 hours | Standard Deviation 9.014 |
| Saxagliptin/Metformin FDC (Fasted) | Metformin T-half and T-max | T-max | 3.08 hours | Standard Deviation 0.762 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Metformin T-half and T-max | T-max | 3.96 hours | Standard Deviation 0.204 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Metformin T-half and T-max | T-Half | 8.62 hours | Standard Deviation 3.069 |
| Saxagliptin/Metformin FDC (Fed) | Metformin T-half and T-max | T-Half | 8.61 hours | Standard Deviation 3.288 |
| Saxagliptin/Metformin FDC (Fed) | Metformin T-half and T-max | T-max | 3.87 hours | Standard Deviation 0.68 |
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) | 50.66 ng*h/mL | Standard Deviation 13.322 |
| Saxagliptin/Metformin FDC (Fasted) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) | 51.74 ng*h/mL | Standard Deviation 12.736 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) | 56.56 ng*h/mL | Standard Deviation 12.778 |
| Saxagliptin/Metformin FDC (Fed) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) | 57.86 ng*h/mL | Standard Deviation 13.222 |
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log\[AUC(INF)\] of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.99, 1.066]Mixed Models Analysis
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log\[AUC(INF)\] of saxagliptin and metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.95% CI: [0.985, 1.06]Mixed Models Analysis
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} | 48.57 ng*h/mL | Standard Deviation 12.864 |
| Saxagliptin/Metformin FDC (Fasted) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} | 49.69 ng*h/mL | Standard Deviation 12.33 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} | 54.59 ng*h/mL | Standard Deviation 12.407 |
| Saxagliptin/Metformin FDC (Fed) | Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} | 55.83 ng*h/mL | Standard Deviation 12.735 |
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted and fed states, linear mixed model analysis was performed on log\[AUC(0-T)\] of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.993, 1.066]Mixed Models Analysis
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log\[AUC(0-T)\] of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.986, 1.058]Mixed Models Analysis
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) | 8.57 ng/mL | Standard Deviation 2.572 |
| Saxagliptin/Metformin FDC (Fasted) | Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) | 8.61 ng/mL | Standard Deviation 2.266 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) | 11.36 ng/mL | Standard Deviation 2.875 |
| Saxagliptin/Metformin FDC (Fed) | Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) | 11.51 ng/mL | Standard Deviation 3.781 |
Comparison: To demonstrate bioequivalence (BE) of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log(Cmax) of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.94, 1.088]Mixed Models Analysis
Comparison: To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log(Cmax) of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.90% CI: [0.929, 1.075]
Primary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-max | 1.78 hours | Standard Deviation 1.21 |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-half | 5.86 hours | Standard Deviation 1.367 |
| Saxagliptin/Metformin FDC (Fasted) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-half | 5.55 hours | Standard Deviation 1.135 |
| Saxagliptin/Metformin FDC (Fasted) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-max | 1.23 hours | Standard Deviation 0.829 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-max | 1.37 hours | Standard Deviation 0.842 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-half | 5.75 hours | Standard Deviation 1.119 |
| Saxagliptin/Metformin FDC (Fed) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-max | 1.42 hours | Standard Deviation 0.862 |
| Saxagliptin/Metformin FDC (Fed) | Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) | T-half | 5.72 hours | Standard Deviation 1.146 |
Secondary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | BMS-510849 Mean AUC (0-INF) | 120.72 ng*h/mL | Standard Deviation 19.826 |
| Saxagliptin/Metformin FDC (Fasted) | BMS-510849 Mean AUC (0-INF) | 122.74 ng*h/mL | Standard Deviation 24.805 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | BMS-510849 Mean AUC (0-INF) | 129.02 ng*h/mL | Standard Deviation 22.988 |
| Saxagliptin/Metformin FDC (Fed) | BMS-510849 Mean AUC (0-INF) | 131.88 ng*h/mL | Standard Deviation 25.908 |
Secondary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | BMS-510849 Mean AUC (0-T) | 112.35 ng*h/mL | Standard Deviation 20.053 |
| Saxagliptin/Metformin FDC (Fasted) | BMS-510849 Mean AUC (0-T) | 113.87 ng*h/mL | Standard Deviation 24.141 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | BMS-510849 Mean AUC (0-T) | 120.31 ng*h/mL | Standard Deviation 22.719 |
| Saxagliptin/Metformin FDC (Fed) | BMS-510849 Mean AUC (0-T) | 123.05 ng*h/mL | Standard Deviation 24.821 |
Secondary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | BMS-510849 Mean Cmax | 16.32 ng/mL | Standard Deviation 5.094 |
| Saxagliptin/Metformin FDC (Fasted) | BMS-510849 Mean Cmax | 16.10 ng/mL | Standard Deviation 4.967 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | BMS-510849 Mean Cmax | 18.40 ng/mL | Standard Deviation 4.14 |
| Saxagliptin/Metformin FDC (Fed) | BMS-510849 Mean Cmax | 18.72 ng/mL | Standard Deviation 4.28 |
Secondary
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
Population: PK data set, all participants who received study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | BMS-510849 Mean T-half and T-max | T-max | 2.40 hours | Standard Deviation 0.965 |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | BMS-510849 Mean T-half and T-max | T-Half | 6.53 hours | Standard Deviation 1.346 |
| Saxagliptin/Metformin FDC (Fasted) | BMS-510849 Mean T-half and T-max | T-Half | 6.93 hours | Standard Deviation 1.284 |
| Saxagliptin/Metformin FDC (Fasted) | BMS-510849 Mean T-half and T-max | T-max | 2.30 hours | Standard Deviation 0.965 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | BMS-510849 Mean T-half and T-max | T-Half | 6.73 hours | Standard Deviation 1.38 |
| Coadministration of Saxagliptin and Metformin IR (Fed) | BMS-510849 Mean T-half and T-max | T-max | 2.35 hours | Standard Deviation 0.774 |
| Saxagliptin/Metformin FDC (Fed) | BMS-510849 Mean T-half and T-max | T-max | 2.53 hours | Standard Deviation 0.727 |
| Saxagliptin/Metformin FDC (Fed) | BMS-510849 Mean T-half and T-max | T-Half | 6.62 hours | Standard Deviation 1.238 |
Secondary
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
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | SAE | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Death | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Participants with at least 1 AE | 6 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | AE leading to discontinuation | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | SAE | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Participants with at least 1 AE | 3 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Death | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | AE leading to discontinuation | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | SAE | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Death | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | AE leading to discontinuation | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Participants with at least 1 AE | 4 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Participants with at least 1 AE | 1 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | AE leading to discontinuation | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Death | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | SAE | 0 participants |
| All Treated Participants | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | SAE | 0 participants |
| All Treated Participants | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Death | 0 participants |
| All Treated Participants | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | Participants with at least 1 AE | 7 participants |
| All Treated Participants | Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation | AE leading to discontinuation | 0 participants |
Secondary
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
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities | 0 participants |
Secondary
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
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Clinically Relevant Vital Sign Abnormalities | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Clinically Relevant Vital Sign Abnormalities | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Clinically Relevant Vital Sign Abnormalities | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Clinically Relevant Vital Sign Abnormalities | 0 participants |
Secondary
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
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High leukocytes | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High BUN | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High creatinine | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Laboratory Marked Abnormalities | Low phosphorus | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High CK | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High urine blood | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High CK | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High urine blood | 1 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High leukocytes | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High creatinine | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Laboratory Marked Abnormalities | Low phosphorus | 1 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participants With Laboratory Marked Abnormalities | High BUN | 1 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Laboratory Marked Abnormalities | Low phosphorus | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Laboratory Marked Abnormalities | High CK | 1 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Laboratory Marked Abnormalities | High leukocytes | 1 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Laboratory Marked Abnormalities | High creatinine | 1 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Laboratory Marked Abnormalities | High BUN | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participants With Laboratory Marked Abnormalities | High urine blood | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Laboratory Marked Abnormalities | Low phosphorus | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Laboratory Marked Abnormalities | High BUN | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Laboratory Marked Abnormalities | High creatinine | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Laboratory Marked Abnormalities | High urine blood | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Laboratory Marked Abnormalities | High CK | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participants With Laboratory Marked Abnormalities | High leukocytes | 0 participants |
| All Treated Participants | Number of Participants With Laboratory Marked Abnormalities | High CK | 1 participants |
| All Treated Participants | Number of Participants With Laboratory Marked Abnormalities | High creatinine | 1 participants |
| All Treated Participants | Number of Participants With Laboratory Marked Abnormalities | High BUN | 1 participants |
| All Treated Participants | Number of Participants With Laboratory Marked Abnormalities | High urine blood | 1 participants |
| All Treated Participants | Number of Participants With Laboratory Marked Abnormalities | Low phosphorus | 1 participants |
| All Treated Participants | Number of Participants With Laboratory Marked Abnormalities | High leukocytes | 1 participants |
Secondary
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
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coadministration of Saxagliptin and Metformin IR (Fasted) | Number of Participant With Clinically Relevant Physical Examination Abnormalities | 0 participants |
| Saxagliptin/Metformin FDC (Fasted) | Number of Participant With Clinically Relevant Physical Examination Abnormalities | 0 participants |
| Coadministration of Saxagliptin and Metformin IR (Fed) | Number of Participant With Clinically Relevant Physical Examination Abnormalities | 0 participants |
| Saxagliptin/Metformin FDC (Fed) | Number of Participant With Clinically Relevant Physical Examination Abnormalities | 0 participants |