Type 2 Diabetes Mellitus
Conditions
Brief summary
To demonstrate the bioequivalence of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet to that of 2.5-mg saxagliptin (Onglyza) and 500-mg metformin (Glucophage, marketed in Canada by Sanofi-Aventis) tablets coadministered to healthy participants in the fasted and fed states.
Interventions
DRUGSaxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week
DRUGSaxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state)
Tablets, oral, 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC), once daily, 1 week
DRUGSaxagliptin, 2.5 mg + Metformin, 500 mg (fed state)
Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week
DRUGSaxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)
Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin FDC, once daily, 1 week
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women, aged 18 to 55 years, inclusive * Healthy participants as determined by a lack of clinically significant deviation from normal in medical history, physical examination, electrocardiograms, and clinical laboratory determinations * Body Mass Index of 18 to 32 kg/m\^2, inclusive
Exclusion criteria
* Any significant acute or chronic medical illness * Current or recent (within 3 months) gastrointestinal disease * Any major surgery within 4 weeks of study drug administration * History of allergy to DPP-4 inhibitors or related compounds * History of allergy or intolerance to metformin or other similar acting agents * Previous exposure to saxagliptin * Exposure to metformin within 3 months pervious to study drug administration * Estimated creatinine clearance of \<80 mL/min using the Cockcroft Gault formula
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
| Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Days 1, 2, and 3 of Periods 1, 2, 3, and 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | At screening visit, Day -1 of Period 1, and at study discharge | Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes. |
| Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate | At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge. | Clinically significant was determined by the investigator. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes. |
| Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4 | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | At screening visit, at Day -1 of Periods 1 through 4, and at discharge | Clinically significant was determined by the investigator. Hematology tests included hemoglobin, hematocrit, red blood cell count, total leukocyte count (including differential), and platelet count. Serum chemistry tests included aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, fasting glucose, total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, and creatine kinase. Urinalysis included protein, glucose, blood, leukocyte esterase, specific gravity, and pH. |
Countries
United States
Participant flow
Pre-assignment details
A total of 27 participants were enrolled and randomly assigned to 1 of 4 treatment sequences: ADBC, BACD, CBDA, or DCAB. One participant withdrew from the study on Day -1 of Period 2 due to a family emergency and returned for early termination assessments on Day 4 of Period 2. She did not receive study drug in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| All Treated All participants who received study medication. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1: Treatment Schedule Phase 1 | Patient withdrew; returned for period 3 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Treated |
|---|---|
| Age, Customized | 32 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized White | 22 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 14 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 | 2 / 27 | 1 / 26 | 7 / 26 | 4 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 26 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 50.28 ng*h/mL | Geometric Coefficient of Variation 24 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 51.60 ng*h/mL | Geometric Coefficient of Variation 23 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 59.00 ng*h/mL | Geometric Coefficient of Variation 20 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 58.94 ng*h/mL | Geometric Coefficient of Variation 19 |
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [97.96, 106.91]
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [96.61, 103.05]
Primary
AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States | 8142.68 ng*h/mL | Geometric Coefficient of Variation 22 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States | 8070.25 ng*h/mL | Geometric Coefficient of Variation 20 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States | 7612.94 ng*h/mL | Geometric Coefficient of Variation 24 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States | 7690.69 ng*h/mL | Geometric Coefficient of Variation 18 |
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.95% CI: [92.9, 105.59]
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.95% CI: [96.82, 109.09]
Primary
AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States | 8035.25 ng*h/mL | Geometric Coefficient of Variation 22 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States | 7906.00 ng*h/mL | Geometric Coefficient of Variation 21 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States | 7497.56 ng*h/mL | Geometric Coefficient of Variation 23 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States | 7654.00 ng*h/mL | Geometric Coefficient of Variation 19 |
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [97.96, 106.91]
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [96.1, 107.88]
Primary
AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 52.17 ng*h/mL | Geometric Coefficient of Variation 24 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 53.73 ng*h/mL | Geometric Coefficient of Variation 23 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 61.31 ng*h/mL | Geometric Coefficient of Variation 20 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States | 60.88 ng*h/mL | Geometric Coefficient of Variation 20 |
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [98.31, 107.16]
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [96.48, 102.04]
Primary
Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | 1058.19 ng/mL | Geometric Coefficient of Variation 23 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | 1044.70 ng/mL | Geometric Coefficient of Variation 25 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | 810.08 ng/mL | Geometric Coefficient of Variation 22 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | 811.94 ng/mL | Geometric Coefficient of Variation 20 |
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states90% CI: [91.29, 107.41]
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [96.86, 103.67]
Primary
Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States | 10.54 ng/mL | Geometric Coefficient of Variation 26 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States | 11.53 ng/mL | Geometric Coefficient of Variation 26 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States | 12.71 ng/mL | Geometric Coefficient of Variation 36 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States | 12.79 ng/mL | Geometric Coefficient of Variation 37 |
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [102.67, 116.85]
Comparison: To demonstrate the bioequivalence of FDC tablet versus coadministration of saxagliptin and metformin tablets in the fasted and fed states, 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 measurements within each subject as repeated measurements allowing for different covariance structures for the fasted and fed states.90% CI: [85.7, 117.56]
Primary
Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 metformin | 11.05 Hours | Standard Deviation 3.94 |
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 saxagliptin | 6.16 Hours | Standard Deviation 1.06 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 saxagliptin | 6.69 Hours | Standard Deviation 0.9 |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 metformin | 13.02 Hours | Standard Deviation 5.37 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 metformin | 10.72 Hours | Standard Deviation 2.61 |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 saxagliptin | 5.99 Hours | Standard Deviation 0.91 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 metformin | 10.96 Hours | Standard Deviation 4.03 |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | t1/2 saxagliptin | 6.15 Hours | Standard Deviation 0.79 |
Primary
Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
Time frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax saxagliptin | 1.00 Hours |
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax metformin | 3.00 Hours |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax metformin | 3.00 Hours |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax saxagliptin | 0.75 Hours |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax saxagliptin | 1.50 Hours |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax metformin | 4.00 Hours |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax saxagliptin | 1.00 Hours |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States | Tmax metformin | 4.00 Hours |
Secondary
Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate
Clinically significant was determined by the investigator. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes.
Time frame: At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge.
Population: All enrolled participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes.
Time frame: At screening visit, Day -1 of Period 1, and at study discharge
Population: All enrolled participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results
Clinically significant was determined by the investigator. Hematology tests included hemoglobin, hematocrit, red blood cell count, total leukocyte count (including differential), and platelet count. Serum chemistry tests included aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, fasting glucose, total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, and creatine kinase. Urinalysis included protein, glucose, blood, leukocyte esterase, specific gravity, and pH.
Time frame: At screening visit, at Day -1 of Periods 1 through 4, and at discharge
Population: All enrolled participants who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Hematology test results | 0 Participants |
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Urinalysis results | 0 Participants |
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Serum chemistry test results | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Hematology test results | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Urinalysis results | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Serum chemistry test results | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Serum chemistry test results | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Hematology test results | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Urinalysis results | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Hematology test results | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Urinalysis results | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results | Serum chemistry test results | 0 Participants |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4
Population: All enrolled participants who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Death | 0 Participants |
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Treatment A: Saxagliptin and Metformin Tablets, Fasted | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Serious Adverse Events | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Death | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Treatment B: Saxagliptin and Metformin FDC, Fasted | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Serious Adverse Events | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Serious Adverse Events | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Death | 0 Participants |
| Treatment C: Saxagliptin and Metformin Tablets, Fed | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Death | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Treatment D: Saxagliptin and Metformin FDC, Fed | Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation | Serious Adverse Events | 0 Participants |