Type 2 Diabetes Mellitus
Conditions
Brief summary
To demonstrate bioequivalence of a 2.5 mg saxagliptin/1000 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 1000 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.
Interventions
DRUGSaxagliptin
Tablet, Oral, 2.5 mg, Once Daily, 1 week
DRUGMetformin IR (glucophage)
Tablets, Oral, 1000 mg, Once Daily, 1 week
DRUGSaxagliptin + Metformin IR (FDC)
Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week
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 PK Parameter Tmax | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. |
| Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. |
| Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. |
| Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. |
| Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. |
| Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. |
| Metformin PK Parameter AUC(INF) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. |
| Metformin PK Parameter AUC(0-T) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. |
| Metformin PK Parameter Cmax | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. |
| Metformin PK Parameter T-HALF | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMS-510849 PK Parameter AUC(INF) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. |
| BMS-510849 PK Parameter AUC(0-T) | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. |
| BMS-510849 PK Parameter Cmax | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. |
| BMS-510849 PK Parameter T-Half | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective plasma concentration versus time data. |
| BMS-510849 PK Parameter T-Max | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. |
| Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study. | An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is 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, or is an important medical event. |
| AEs of Special Interest | AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). | See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class \[SOC\]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity. |
| Number of Participants With Marked Laboratory Abnormalities (MA) | Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. | Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10\^3 c/uL; absolute neutrophils/bands LN, 1.500x10\^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L. |
| Number of Participants With Marked Urinalysis Abnormalities | Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. | Protein, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). Glucose, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). Blood, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). White Blood Cell (WBC), Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 2+, then \>= 4+). Red Blood Cell (RBC), Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 2+, then \>= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.) |
| Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation | 12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs. |
Countries
United States
Participant flow
Pre-assignment details
58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled and Treated Participants | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Did not Return for the Clinic Visit | 2 |
| Overall Study | No Longer Met Study Criteria | 1 |
| Overall Study | Personal Reasons | 1 |
Baseline characteristics
| Characteristic | All Enrolled and Treated Participants |
|---|---|
| Age, Continuous | 30 years STANDARD_DEVIATION 6 |
| Body Mass Index | 26.5 kg/m^2 STANDARD_DEVIATION 3.8 |
| Race/Ethnicity, Customized Black | 4 participants |
| Race/Ethnicity, Customized White | 20 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 16 Participants |
| weight | 79.9 kg STANDARD_DEVIATION 15 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 2 / 19 | 2 / 21 | 3 / 24 | 0 / 34 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 21 | 0 / 24 | 0 / 34 |
Outcome results
Primary
Metformin PK Parameter AUC(0-T)
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Metformin PK Parameter AUC(0-T) | 13238.43 ng*h/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Metformin PK Parameter AUC(0-T) | 12400.41 ng*h/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Metformin PK Parameter AUC(0-T) | 12124.31 ng*h/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Metformin PK Parameter AUC(0-T) | 11996.88 ng*h/mL |
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.906, 1.02]
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.92, 1.032]
Primary
Metformin PK Parameter AUC(INF)
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Metformin PK Parameter AUC(INF) | 13363.46 ng*h/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Metformin PK Parameter AUC(INF) | 12677.92 ng*h/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Metformin PK Parameter AUC(INF) | 12357.87 ng*h/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Metformin PK Parameter AUC(INF) | 12126.19 ng*h/mL |
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.921, 1.03]
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.915, 1.02]
Primary
Metformin PK Parameter Cmax
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Metformin PK Parameter Cmax | 2004.99 ng/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Metformin PK Parameter Cmax | 1830.76 ng/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Metformin PK Parameter Cmax | 1666.55 ng/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Metformin PK Parameter Cmax | 1642.90 ng/mL |
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.864, 1.016]
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.891, 1.042]
Primary
Metformin PK Parameter T-HALF
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Metformin PK Parameter T-HALF | 8.43 hours | Standard Deviation 2.956 |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Metformin PK Parameter T-HALF | 10.58 hours | Standard Deviation 8.895 |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Metformin PK Parameter T-HALF | 11.78 hours | Standard Deviation 5.999 |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Metformin PK Parameter T-HALF | 7.63 hours | Standard Deviation 2.309 |
Primary
Metformin PK Parameter Tmax
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Metformin PK Parameter Tmax | 2.00 hours |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Metformin PK Parameter Tmax | 2.98 hours |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Metformin PK Parameter Tmax | 4.00 hours |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Metformin PK Parameter Tmax | 4.00 hours |
Primary
Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF])
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | 47.25 ng*h/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | 48.91 ng*h/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | 52.89 ng*h/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | 51.11 ng*h/mL |
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [1.009, 1.075]
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.958, 1.019]
Primary
Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T])
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | 44.90 ng*h/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | 46.57 ng*h/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | 50.50 ng*h/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | 49.09 ng*h/mL |
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [1.013, 1.077]
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.962, 1.022]
Primary
Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax)
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | 8.58 ng/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | 9.09 ng/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | 10.97 ng/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | 10.80 ng/mL |
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.978, 1.185]
Comparison: To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log\[AUC(INF)\] and log\[AUC(0-T)\] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.90% CI: [0.9, 1.083]
Primary
Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF)
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | 6.66 hours | Standard Deviation 1.185 |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | 6.34 hours | Standard Deviation 0.941 |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | 6.47 hours | Standard Deviation 1.529 |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | 5.78 hours | Standard Deviation 1.333 |
Primary
Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax)
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | 1.50 hours |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | 0.75 hours |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | 1.00 hours |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | 1.50 hours |
Secondary
AEs of Special Interest
See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class \[SOC\]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity.
Time frame: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days).
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | AEs of Special Interest | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | AEs of Special Interest | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | AEs of Special Interest | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | AEs of Special Interest | 0 participants |
Secondary
BMS-510849 PK Parameter AUC(0-T)
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter AUC(0-T) | 108.31 ng*h/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter AUC(0-T) | 106.11 ng*h/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter AUC(0-T) | 117.42 ng*h/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter AUC(0-T) | 117.43 ng*h/mL |
Secondary
BMS-510849 PK Parameter AUC(INF)
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter AUC(INF) | 118.54 ng*h/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter AUC(INF) | 116.19 ng*h/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter AUC(INF) | 127.67 ng*h/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter AUC(INF) | 127.25 ng*h/mL |
Secondary
BMS-510849 PK Parameter Cmax
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter Cmax | 16.77 ng/mL |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter Cmax | 15.17 ng/mL |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter Cmax | 18.24 ng/mL |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter Cmax | 18.58 ng/mL |
Secondary
BMS-510849 PK Parameter T-Half
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter T-Half | 8.05 hours | Standard Deviation 1.427 |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter T-Half | 7.31 hours | Standard Deviation 1.369 |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter T-Half | 7.48 hours | Standard Deviation 1.504 |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter T-Half | 7.35 hours | Standard Deviation 1.622 |
Secondary
BMS-510849 PK Parameter T-Max
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Population: Treated participants with PK measures
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter T-Max | 2.00 hours |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | BMS-510849 PK Parameter T-Max | 2.00 hours |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter T-Max | 2.00 hours |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | BMS-510849 PK Parameter T-Max | 2.00 hours |
Secondary
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is 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, or is an important medical event.
Time frame: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | AEs | 5 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Discontinuations dues to AEs | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | SAEs | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Deaths | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | SAEs | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | AEs | 2 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Deaths | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Discontinuations dues to AEs | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | SAEs | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Deaths | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Discontinuations dues to AEs | 1 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | AEs | 4 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Discontinuations dues to AEs | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | AEs | 3 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | Deaths | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | SAEs | 0 participants |
Secondary
Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities
12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs.
Time frame: At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation
Population: Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | ECG Abnormalities | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Vital Sign Abnormalities | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Physical Finding Abnormalities | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Physical Finding Abnormalities | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | ECG Abnormalities | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Vital Sign Abnormalities | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Vital Sign Abnormalities | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Physical Finding Abnormalities | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | ECG Abnormalities | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Vital Sign Abnormalities | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | ECG Abnormalities | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | Physical Finding Abnormalities | 0 participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities (MA)
Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10\^3 c/uL; absolute neutrophils/bands LN, 1.500x10\^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L.
Time frame: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.
Population: Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Creatine Kinase - High (>1.5 ULN) | 1 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Blood Urea Nitrogen - High (1.1 * ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Leukocytes - High(>1.2 * upper limit normal [ULN]) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Alanine Aminotransferase - High (>1.25 * ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Lactate Dehydrogenase - High (>1.25 ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Aspartate Aminotransferase - High (>1.25 * ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Abs. Neutrophils/Bands-Low (<=lower LN [LLN]) | 1 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Alanine Aminotransferase - High (>1.25 * ULN) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Leukocytes - High(>1.2 * upper limit normal [ULN]) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Abs. Neutrophils/Bands-Low (<=lower LN [LLN]) | 1 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Aspartate Aminotransferase - High (>1.25 * ULN) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Blood Urea Nitrogen - High (1.1 * ULN) | 1 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Creatine Kinase - High (>1.5 ULN) | 1 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Laboratory Abnormalities (MA) | Lactate Dehydrogenase - High (>1.25 ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Leukocytes - High(>1.2 * upper limit normal [ULN]) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Alanine Aminotransferase - High (>1.25 * ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Blood Urea Nitrogen - High (1.1 * ULN) | 1 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Aspartate Aminotransferase - High (>1.25 * ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Lactate Dehydrogenase - High (>1.25 ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Creatine Kinase - High (>1.5 ULN) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Abs. Neutrophils/Bands-Low (<=lower LN [LLN]) | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Creatine Kinase - High (>1.5 ULN) | 2 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Lactate Dehydrogenase - High (>1.25 ULN) | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Alanine Aminotransferase - High (>1.25 * ULN) | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Aspartate Aminotransferase - High (>1.25 * ULN) | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Leukocytes - High(>1.2 * upper limit normal [ULN]) | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Abs. Neutrophils/Bands-Low (<=lower LN [LLN]) | 1 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Laboratory Abnormalities (MA) | Blood Urea Nitrogen - High (1.1 * ULN) | 0 participants |
Secondary
Number of Participants With Marked Urinalysis Abnormalities
Protein, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). Glucose, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). Blood, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). White Blood Cell (WBC), Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 2+, then \>= 4+). Red Blood Cell (RBC), Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 2+, then \>= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.)
Time frame: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.
Population: Number of Participants Analyzed=treated participants; n=number of participants evaluated for this measure (among the 6 participants who had the urinary WBC and RBC test, there are only 2 had a pre-study evaluation, and were therefore evaluable for these measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | White Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Blood, Urine (n=19, 19, 20, 21) | 1 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Red Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Protein, Urine (n=19, 19, 20, 21) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Glucose, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Glucose, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Protein, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | White Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Blood, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Number of Participants With Marked Urinalysis Abnormalities | Red Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Blood, Urine (n=19, 19, 20, 21) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Protein, Urine (n=19, 19, 20, 21) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Red Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | White Blood Cells, Urine (n=2, 2, 2, 2) | 1 participants |
| 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Glucose, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | White Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Blood, Urine (n=19, 19, 20, 21) | 2 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Protein, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Glucose, Urine (n=19, 19, 20, 21) | 0 participants |
| FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Number of Participants With Marked Urinalysis Abnormalities | Red Blood Cells, Urine (n=2, 2, 2, 2) | 0 participants |