Type 2 Diabetes Mellitus
Conditions
Brief summary
To demonstrate bioequivalence of a 2.5 mg saxagliptin/850 mg metformin fixed dose combination (FDC) tablet relative to the 2.5 mg saxagliptin tablet and 850 mg metformin (Glucophage Marketed by Merck-Serono) tablet co-administered to healthy subjects in the fasted and fed condition.
Interventions
DRUGsaxagliptin
Tablets, Oral, 2.5 mg, once daily, single dose
DRUGmetformin
Tablets, Oral, 850 mg, once daily, single dose
DRUGsaxagliptin + metformin (FDC tablet)
Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose
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 ages 18 to 55 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/m\^2, inclusive. BMI = weight (kg)/ \[height (m)\]\^2
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 a dipeptidyl peptidase-IV (DPP4) inhibitor or related compound * 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 \< 80 mL/min using the Cockcroft Gault formula
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. |
| Metformin PK Parameter Cmax | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma. |
| Metformin PK Parameter AUC(0-inf) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. |
| Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC\[0-t\] is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. |
| 5-hydroxy Saxagliptin PK Parameter AUC(0-inf) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. |
| 5-hydroxy Saxagliptin PK Parameter Cmax | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma. |
| 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma. |
| 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration. |
| Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening). | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. |
| Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). | Abnormalities that were considered clinically significant and/or reported as an AE by the investigator. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Metformin PK Parameter Tmax | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration. |
| Saxagliptin PK Parameter Tmax | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration. |
| Saxagliptin PK Parameter T1/2 | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma. |
| Saxagliptin PK Parameter AUC(0-t) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-t) is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. |
| Metformin PK Parameter T1/2 | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma. |
| Metformin PK Parameter AUC(0-t) | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-t) is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. |
Countries
United States
Participant flow
Recruitment details
Participants (N = 24) who met all of the inclusion and none of the exclusion criteria were recruited from a single site in the United States.
Pre-assignment details
Participants were screened for eligibility within 21 days before Day 1 of period 1. On Day -1 of each period, the participants were admitted to the clinical facility and confined for 4 days. All the 24 participants were randomly assigned to 1 of 4 treatment sequences (ADBC, BACD, CBDA, or DCAB). The washout between each dose was at least 7 days.
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled and Treated Participants | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 3 | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Enrolled and Treated Participants |
|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 10.61 |
| Body Mass Index (BMI) | 27.4 kg/m^2 STANDARD_DEVIATION 3.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 170.2 cm STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 16 Participants |
| Weight | 79.7 kg STANDARD_DEVIATION 13.7 |
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 | 4 / 24 | 5 / 24 | 3 / 23 | 4 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Metformin PK Parameter AUC(0-inf)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Metformin PK Parameter AUC(0-inf) | 11998.00 ng*hr/mL | Geometric Coefficient of Variation 23.68 |
| Treatment B | Metformin PK Parameter AUC(0-inf) | 12271.61 ng*hr/mL | Geometric Coefficient of Variation 20.42 |
| Treatment C | Metformin PK Parameter AUC(0-inf) | 11988.30 ng*hr/mL | Geometric Coefficient of Variation 16.94 |
| Treatment D | Metformin PK Parameter AUC(0-inf) | 11838.11 ng*hr/mL | Geometric Coefficient of Variation 18.18 |
Comparison: If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 99% power to conclude BE with respect to each of Cmax and AUC0-inf. If there was a 5% difference, then 20 subjects would provide 97% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [97.26, 107.18]
Comparison: If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 99% power to conclude BE with respect to each of Cmax and AUC0-inf. If there was a 5% difference, then 20 subjects would provide 97% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [96.23, 102.21]
Comparison: Geometric least squares mean for Treatment A.
Comparison: Geometric least squares means for Treatment B.
Comparison: Geometric least squares means for Treatment C.
Comparison: Geometric least squares means for Treatment D.
Primary
Metformin PK Parameter Cmax
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Metformin PK Parameter Cmax | 1724.38 ng/mL | Geometric Coefficient of Variation 25.49 |
| Treatment B | Metformin PK Parameter Cmax | 1715.79 ng/mL | Geometric Coefficient of Variation 23.59 |
| Treatment C | Metformin PK Parameter Cmax | 1571.21 ng/mL | Geometric Coefficient of Variation 15.64 |
| Treatment D | Metformin PK Parameter Cmax | 1541.76 ng/mL | Geometric Coefficient of Variation 17.45 |
Comparison: If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 99% power to conclude BE with respect to each of Cmax and AUC0-inf. If there was a 5% difference, then 20 subjects would provide 97% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [90.41, 109.5]
Comparison: If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 99% power to conclude BE with respect to each of Cmax and AUC0-inf. If there was a 5% difference, then 20 subjects would provide 97% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [94.28, 102.32]
Comparison: Geometric least squares means for Treatment A.
Comparison: Geometric least squares means for Treatment B.
Comparison: Geometric least squares means for Treatment C.
Comparison: Geometric least squares means for Treatment D.
Primary
Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | 49.23 ng*hr/mL | Geometric Coefficient of Variation 18.52 |
| Treatment B | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | 49.94 ng*hr/mL | Geometric Coefficient of Variation 19.72 |
| Treatment C | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | 52.50 ng*hr/mL | Geometric Coefficient of Variation 17.95 |
| Treatment D | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | 53.15 ng*hr/mL | Geometric Coefficient of Variation 17.81 |
Comparison: If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 98% and 99% power to conclude bioequivalence (BE) with respect to Cmax and AUC0-inf, respectively. If there was a 5% difference, then 20 participants would have provided 93% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [98.17, 104.84]
Comparison: If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 98% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively. If there was a 5% difference, then 20 participants would have provided 93% and 99% power to conclude BE with respect to Cmax and AUC0-inf,respectively.90% CI: [99.53, 105.42]
Comparison: Geometric least squares means for Treatment A.
Comparison: Geometric least squares means for Treatment B.
Comparison: Geometric least squares means for Treatment C.
Comparison: Geometric least squares means for Treatment D.
Primary
Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax) | 9.73 ng/mL | Geometric Coefficient of Variation 20.44 |
| Treatment B | Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax) | 9.97 ng/mL | Geometric Coefficient of Variation 29.07 |
| Treatment C | Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax) | 10.25 ng/mL | Geometric Coefficient of Variation 26.87 |
| Treatment D | Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax) | 10.88 ng/mL | Geometric Coefficient of Variation 23.72 |
Comparison: If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 98% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively. If there was a 5% difference, then 20 participants would have provided 93% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [94.68, 110.88]
Comparison: If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of saxagliptin and metformin tablets under both fasted and fed conditions, then 20 participants would have provided 98% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively. If there was a 5% difference, then 20 participants would have provided 93% and 99% power to conclude BE with respect to Cmax and AUC0-inf, respectively.90% CI: [98.43, 114.66]
Comparison: Geometric least squares means for Treatment A.
Comparison: Geometric least squares means for Treatment B.
Comparison: Geometric least squares means for Treatment C.
Comparison: Geometric least squares means for Treatment D.
Secondary
5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC\[0-t\] is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) | 109.60 ng*hr/mL | Geometric Coefficient of Variation 25.81 |
| Treatment B | 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) | 110.61 ng*hr/mL | Geometric Coefficient of Variation 22.77 |
| Treatment C | 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) | 113.15 ng*hr/mL | Geometric Coefficient of Variation 26.53 |
| Treatment D | 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) | 117.04 ng*hr/mL | Geometric Coefficient of Variation 25.74 |
Secondary
5-hydroxy Saxagliptin PK Parameter AUC(0-inf)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | 5-hydroxy Saxagliptin PK Parameter AUC(0-inf) | 118.58 ng*hr/mL | Geometric Coefficient of Variation 24.08 |
| Treatment B | 5-hydroxy Saxagliptin PK Parameter AUC(0-inf) | 119.54 ng*hr/mL | Geometric Coefficient of Variation 21.16 |
| Treatment C | 5-hydroxy Saxagliptin PK Parameter AUC(0-inf) | 121.99 ng*hr/mL | Geometric Coefficient of Variation 25.42 |
| Treatment D | 5-hydroxy Saxagliptin PK Parameter AUC(0-inf) | 125.54 ng*hr/mL | Geometric Coefficient of Variation 24.82 |
Secondary
5-hydroxy Saxagliptin PK Parameter Cmax
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | 5-hydroxy Saxagliptin PK Parameter Cmax | 16.83 ng/mL | Geometric Coefficient of Variation 32.95 |
| Treatment B | 5-hydroxy Saxagliptin PK Parameter Cmax | 16.72 ng/mL | Geometric Coefficient of Variation 32.92 |
| Treatment C | 5-hydroxy Saxagliptin PK Parameter Cmax | 17.35 ng/mL | Geometric Coefficient of Variation 32.95 |
| Treatment D | 5-hydroxy Saxagliptin PK Parameter Cmax | 18.59 ng/mL | Geometric Coefficient of Variation 30.78 |
Secondary
5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2) | 7.58 hr | Standard Deviation 1.32 |
| Treatment B | 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2) | 7.58 hr | Standard Deviation 1.35 |
| Treatment C | 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2) | 7.48 hr | Standard Deviation 1.1 |
| Treatment D | 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2) | 7.22 hr | Standard Deviation 1.01 |
Secondary
5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) | 2.21 hr | Standard Deviation 0.75 |
| Treatment B | 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) | 1.86 hr | Standard Deviation 0.71 |
| Treatment C | 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) | 2.65 hr | Standard Deviation 0.83 |
| Treatment D | 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) | 2.46 hr | Standard Deviation 0.72 |
Secondary
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs).
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
Population: All participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Number of Participants With at Least 1 AE | 4 participants |
| Treatment A | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Discontinuation Due to AE | 1 participants |
| Treatment A | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Deaths | 0 participants |
| Treatment A | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | SAEs | 0 participants |
| Treatment B | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Discontinuation Due to AE | 0 participants |
| Treatment B | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Deaths | 0 participants |
| Treatment B | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | SAEs | 0 participants |
| Treatment B | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Number of Participants With at Least 1 AE | 5 participants |
| Treatment C | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Deaths | 0 participants |
| Treatment C | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Discontinuation Due to AE | 0 participants |
| Treatment C | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | SAEs | 0 participants |
| Treatment C | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Number of Participants With at Least 1 AE | 3 participants |
| Treatment D | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | SAEs | 0 participants |
| Treatment D | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Discontinuation Due to AE | 0 participants |
| Treatment D | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Number of Participants With at Least 1 AE | 4 participants |
| Treatment D | Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs). | Deaths | 0 participants |
Secondary
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Abnormalities that were considered clinically significant and/or reported as an AE by the investigator.
Time frame: From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening).
Population: All participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Clinical Laboratory Abnormalities | 0 participants |
| Treatment A | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Vital Sign Abnormalities | 0 participants |
| Treatment A | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Physical Examination Abnormalities | 0 participants |
| Treatment A | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | 12-Lead ECG Abnormalities | 0 participants |
| Treatment B | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Vital Sign Abnormalities | 0 participants |
| Treatment B | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Physical Examination Abnormalities | 0 participants |
| Treatment B | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | 12-Lead ECG Abnormalities | 0 participants |
| Treatment B | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Clinical Laboratory Abnormalities | 0 participants |
| Treatment C | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Physical Examination Abnormalities | 0 participants |
| Treatment C | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Vital Sign Abnormalities | 0 participants |
| Treatment C | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | 12-Lead ECG Abnormalities | 0 participants |
| Treatment C | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Clinical Laboratory Abnormalities | 1 participants |
| Treatment D | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | 12-Lead ECG Abnormalities | 0 participants |
| Treatment D | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Vital Sign Abnormalities | 0 participants |
| Treatment D | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Clinical Laboratory Abnormalities | 0 participants |
| Treatment D | Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities | Physical Examination Abnormalities | 0 participants |
Other Pre-specified
Metformin PK Parameter AUC(0-t)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-t) is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Metformin PK Parameter AUC(0-t) | 11826.52 ng*hr/mL | Geometric Coefficient of Variation 23.86 |
| Treatment B | Metformin PK Parameter AUC(0-t) | 11875.08 ng*hr/mL | Geometric Coefficient of Variation 21.47 |
| Treatment C | Metformin PK Parameter AUC(0-t) | 11796.60 ng*hr/mL | Geometric Coefficient of Variation 17.03 |
| Treatment D | Metformin PK Parameter AUC(0-t) | 11681.05 ng*hr/mL | Geometric Coefficient of Variation 17.59 |
90% CI: [95.4, 105.68]
90% CI: [96.19, 102.02]
Other Pre-specified
Metformin PK Parameter T1/2
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Metformin PK Parameter T1/2 | 10.94 hr | Standard Deviation 4.13 |
| Treatment B | Metformin PK Parameter T1/2 | 13.15 hr | Standard Deviation 6.67 |
| Treatment C | Metformin PK Parameter T1/2 | 10.82 hr | Standard Deviation 3.18 |
| Treatment D | Metformin PK Parameter T1/2 | 11.13 hr | Standard Deviation 3.08 |
Other Pre-specified
Metformin PK Parameter Tmax
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Metformin PK Parameter Tmax | 2.41 hr | Standard Deviation 0.78 |
| Treatment B | Metformin PK Parameter Tmax | 2.54 hr | Standard Deviation 0.92 |
| Treatment C | Metformin PK Parameter Tmax | 3.74 hr | Standard Deviation 0.54 |
| Treatment D | Metformin PK Parameter Tmax | 3.74 hr | Standard Deviation 0.45 |
Other Pre-specified
Saxagliptin PK Parameter AUC(0-t)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-t) is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Saxagliptin PK Parameter AUC(0-t) | 47.15 ng*hr/mL | Geometric Coefficient of Variation 17.98 |
| Treatment B | Saxagliptin PK Parameter AUC(0-t) | 47.83 ng*hr/mL | Geometric Coefficient of Variation 19.77 |
| Treatment C | Saxagliptin PK Parameter AUC(0-t) | 50.69 ng*hr/mL | Geometric Coefficient of Variation 17.74 |
| Treatment D | Saxagliptin PK Parameter AUC(0-t) | 51.37 ng*hr/mL | Geometric Coefficient of Variation 17.63 |
90% CI: [98.07, 104.9]
90% CI: [99.56, 105.57]
Other Pre-specified
Saxagliptin PK Parameter T1/2
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Saxagliptin PK Parameter T1/2 | 6.45 hr | Standard Deviation 1 |
| Treatment B | Saxagliptin PK Parameter T1/2 | 6.21 hr | Standard Deviation 1.25 |
| Treatment C | Saxagliptin PK Parameter T1/2 | 5.86 hr | Standard Deviation 0.92 |
| Treatment D | Saxagliptin PK Parameter T1/2 | 6.09 hr | Standard Deviation 0.94 |
Other Pre-specified
Saxagliptin PK Parameter Tmax
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Time frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Population: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Saxagliptin PK Parameter Tmax | 1.38 hr | Standard Deviation 0.79 |
| Treatment B | Saxagliptin PK Parameter Tmax | 0.96 hr | Standard Deviation 0.61 |
| Treatment C | Saxagliptin PK Parameter Tmax | 1.94 hr | Standard Deviation 0.95 |
| Treatment D | Saxagliptin PK Parameter Tmax | 1.48 hr | Standard Deviation 0.58 |