Type2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to examine the drug-drug interaction in your body when given the study drug, bexagliflozin, with three commonly used ant-diabetic medications, metformin, glimepiride or sitagliptin. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when taken with metformin, glimepiride or sitagliptin.
Detailed description
A total of 54 healthy subjects were enrolled and assigned to one of three groups of eighteen. Each group participated in one of three open-label, randomized, three treatment period, crossover studies: * Group 1: Bexagliflozin/metformin drug-drug interaction (DDI) * Group 2: Bexagliflozin/glimepiride DDI * Group 3: Bexagliflozin/sitagliptin DDI For each Group, every subject received a single dose of bexagliflozin tablet, 20 mg, alone, a single dose of an oral hypoglycemic agent (OHA) (1000 mg metformin, 2 mg glimepiride, or 100 mg sitagliptin) alone, and the combination of both (bexagliflozin tablet and OHA) alternately in a crossover fashion, with three treatment periods separated by a washout period of at least 7 days. Within each Group, subjects were randomized to one of six treatment sequences in an equal ratio. To prevent hypoglycemia, subjects assigned to Group 2 (bexagliflozin/glimepiride DDI) received approximately 300 mL of a solution containing 50 g of glucose with study medication at the time of dosing, as well as approximately 75 mL of a solution containing 12.5 g of glucose every 15 minutes for 4 hours post-dose. For each treatment period in Group 1 (bexagliflozin/metformin DDI) and Group 2 (bexagliflozin/glimepiride DDI), subjects were admitted to the clinic on the day before dosing and stayed in the clinic until 48 h post-dose. For Group 3 (bexagliflozin/sitagliptin DDI), subjects stayed in the clinic until 72 h post-dose. For all Groups, blood samples for PK analysis were collected in each period prior to dosing (pre-dose) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose. For Group 3, PK blood samples were also collected at 60 and 72 h post-dose. Plasma concentrations of bexagliflozin and OHAs were determined by validated liquid chromatography tandem mass spectrometry (LC MS/MS) assays. Urine samples for PD analysis were collected in 12 h intervals. For all Groups, urine samples were collected pre-dose (-12 to 0 h) and post-dose at 0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h. For Group 3, additional samples at 48 to 60 h and 60 to 72 h post-dose were collected.
Interventions
DRUGBexagliflozin
Bexagliflozin tablets, 20 mg
DRUGMetformin
1000 mg metformin
DRUGGlimepiride
4 mg glimepiride
DRUGSitagliptin
100 mg sitagliptin
Sponsors
Theracos
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2 2. Subjects who are non-smokers for at least 3 months prior to screening 3. Subjects who are willing and able to be confined to the clinical research facility as required by the protocol
Exclusion criteria
1. Subjects with a clinically significant history of allergy to drugs or latex. 2. Subjects with a history of alcohol or drug dependence in the past 12 months. 3. Subjects who have donated a significant amount of blood in the past 2 months 4. Female subjects who are pregnant or breastfeeding 5. Subjects who are not willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic 6. Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer 7. Subjects who had previously received anti-diabetic medication, including metformin, sitagliptin, glimepiride or drugs of the same class (i.e. biguanides, DPP-4 inhibitors or sulfonylureas), or SGLT2 inhibitors, in the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Plasma Concentration) | Up to 72 hours | Whole venous blood samples of 5 mL were be collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. Pharmacokinetic (PK) blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Cmax was obtained directly from experimental observations. |
| Tmax (Time of Maximum Observed Plasma Concentration) | Up to 72 hours | Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Tmax was obtained directly from experimental observations. |
| T1/2 (Apparent Terminal Elimination Half-life) | Up to 72 hours | Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. T1/2 was obtained directly from experimental observations. |
| AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Up to 72 hours | Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. AUC0-inf was estimated for each subject. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Glucose Excretion up to 0-72 hr | up to 0-72 hr | Pre-dose urine samples were collected from -12 to 0 h for baseline measurement. Subjects was instructed to empty their bladder prior to dosing. Post-dose urine was collected in 4 batches for Groups 1 and 2 at 0 to 12 h, 12 to 24 h, 24 o 36 h, and 36 to 48 h collections. Post-dose urine was collected in batches for Group 3 at 0 to 12 h, 12 to 24 h, 24 to 36 h, 36 to 48 h, 48 to 60 h and 60 to 72 h. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Bexagliflozin + Metformin Bexagliflozin tablets 20 mg alone, Metformin tablets 1000 mg alone, or Bexagliflozin 20 mg + Metformin 1000 mg | 18 |
| Group 2: Bexagliflozin + Glimepiride Bexagliflozin tablets 20 mg alone, Glimepiride tablets 2 mg alone, or Bexagliflozin 20 mg + Glimepiride 2 mg | 18 |
| Group 3: Bexagliflozin + Sitagliptin Bexagliflozin tablets 20 mg alone, Sitagliptin 100 mg alone, or Bexagliflozin 20 mg + Sitagliptin 100 mg | 18 |
| Total | 54 |
Baseline characteristics
| Characteristic | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin + Sitagliptin | Total |
|---|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 15.69 | 37.6 years STANDARD_DEVIATION 8.25 | 43.6 years STANDARD_DEVIATION 14.52 | 41.1 years STANDARD_DEVIATION 13.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | 17 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 173.3 cm STANDARD_DEVIATION 9.16 | 172.3 cm STANDARD_DEVIATION 6.45 | 170.5 cm STANDARD_DEVIATION 8.37 | 172.0 cm STANDARD_DEVIATION 8.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 12 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 9 Participants | 34 Participants |
| Weight | 79.0 kg STANDARD_DEVIATION 11.75 | 77.9 kg STANDARD_DEVIATION 12.37 | 79.0 kg STANDARD_DEVIATION 13.21 | 78.6 kg STANDARD_DEVIATION 12.23 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 3 / 18 | 11 / 18 | 13 / 18 | 6 / 18 | 2 / 18 | 4 / 18 | 3 / 18 | 1 / 18 | 2 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. AUC0-inf was estimated for each subject.
Time frame: Up to 72 hours
Population: The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Bexagliflozin Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Bexagliflozin PK parameters | 1154.4 h*ng/mL | Geometric Coefficient of Variation 35.1 |
| Group 1: Metformin Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Metformin PK parameters | 13351.9 h*ng/mL | Geometric Coefficient of Variation 22.5 |
| Group 1: Bexagliflozin + Metformin | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Bexagliflozin PK parameters | 1008.6 h*ng/mL | Geometric Coefficient of Variation 40.2 |
| Group 1: Bexagliflozin + Metformin | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Metformin PK parameters | 13784.6 h*ng/mL | Geometric Coefficient of Variation 26 |
| Group 2: Bexagliflozin Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Bexagliflozin PK parameters | 1204.9 h*ng/mL | Geometric Coefficient of Variation 48.6 |
| Group 2: Glimepiride Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Glimepiride PK parameters | 496.1 h*ng/mL | Geometric Coefficient of Variation 53.3 |
| Group 2: Bexagliflozin + Glimepiride | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Bexagliflozin PK parameters | 1162.2 h*ng/mL | Geometric Coefficient of Variation 47.8 |
| Group 2: Bexagliflozin + Glimepiride | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Glimepiride PK parameters | 633.0 h*ng/mL | Geometric Coefficient of Variation 38.5 |
| Group 3: Bexagliflozin Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Bexagliflozin PK parameters | 1011.8 h*ng/mL | Geometric Coefficient of Variation 21.5 |
| Group 3: Sitagliptin Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Sitagliptin PK parameters | 3579.6 h*ng/mL | Geometric Coefficient of Variation 14.7 |
| Group 3: Bexagliflozin + Sitagliptin | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Sitagliptin PK parameters | 3692.8 h*ng/mL | Geometric Coefficient of Variation 16.9 |
| Group 3: Bexagliflozin + Sitagliptin | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Bexagliflozin PK parameters | 1158.1 h*ng/mL | Geometric Coefficient of Variation 21.9 |
Comparison: Geometric LS Mean was used as PK parameters90% CI: [80.02, 95.38]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [94.59, 112.68]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [80.34, 111.06]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [110.33, 146.62]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [107.61, 118.86]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [99.3, 107.17]
Primary
Cmax (Maximum Observed Plasma Concentration)
Whole venous blood samples of 5 mL were be collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. Pharmacokinetic (PK) blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Cmax was obtained directly from experimental observations.
Time frame: Up to 72 hours
Population: The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Bexagliflozin Alone | Cmax (Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 124.6 ng/mL | Geometric Coefficient of Variation 43.7 |
| Group 1: Metformin Alone | Cmax (Maximum Observed Plasma Concentration) | Metformin PK parameters | 2067.6 ng/mL | Geometric Coefficient of Variation 27.2 |
| Group 1: Bexagliflozin + Metformin | Cmax (Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 135.5 ng/mL | Geometric Coefficient of Variation 40 |
| Group 1: Bexagliflozin + Metformin | Cmax (Maximum Observed Plasma Concentration) | Metformin PK parameters | 1965.2 ng/mL | Geometric Coefficient of Variation 33.6 |
| Group 2: Bexagliflozin Alone | Cmax (Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 158.6 ng/mL | Geometric Coefficient of Variation 53.9 |
| Group 2: Glimepiride Alone | Cmax (Maximum Observed Plasma Concentration) | Glimepiride PK parameters | 59.9 ng/mL | Geometric Coefficient of Variation 32.2 |
| Group 2: Bexagliflozin + Glimepiride | Cmax (Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 143.7 ng/mL | Geometric Coefficient of Variation 37.9 |
| Group 2: Bexagliflozin + Glimepiride | Cmax (Maximum Observed Plasma Concentration) | Glimepiride PK parameters | 67.1 ng/mL | Geometric Coefficient of Variation 29.5 |
| Group 3: Bexagliflozin Alone | Cmax (Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 117.1 ng/mL | Geometric Coefficient of Variation 34.6 |
| Group 3: Sitagliptin Alone | Cmax (Maximum Observed Plasma Concentration) | Sitagliptin PK parameters | 356.6 ng/mL | Geometric Coefficient of Variation 22.3 |
| Group 3: Bexagliflozin + Sitagliptin | Cmax (Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 148.3 ng/mL | Geometric Coefficient of Variation 22.1 |
| Group 3: Bexagliflozin + Sitagliptin | Cmax (Maximum Observed Plasma Concentration) | Sitagliptin PK parameters | 351.2 ng/mL | Geometric Coefficient of Variation 32.9 |
Comparison: Geometric Least Square (LS) Mean was used as PK parameters95% CI: [94.35, 125.3]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [84.73, 106.63]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [70.39, 113.65]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [97.02, 129.19]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [112.08, 143.17]
Comparison: Geometric LS Mean was used as PK parameters90% CI: [84.9, 114.23]
Primary
T1/2 (Apparent Terminal Elimination Half-life)
Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. T1/2 was obtained directly from experimental observations.
Time frame: Up to 72 hours
Population: The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Bexagliflozin Alone | T1/2 (Apparent Terminal Elimination Half-life) | Bexagliflozin PK parameters | 10.3 hours | Geometric Coefficient of Variation 30.4 |
| Group 1: Metformin Alone | T1/2 (Apparent Terminal Elimination Half-life) | Metformin PK parameters | 9.0 hours | Geometric Coefficient of Variation 31.8 |
| Group 1: Bexagliflozin + Metformin | T1/2 (Apparent Terminal Elimination Half-life) | Metformin PK parameters | 10.2 hours | Geometric Coefficient of Variation 32.5 |
| Group 1: Bexagliflozin + Metformin | T1/2 (Apparent Terminal Elimination Half-life) | Bexagliflozin PK parameters | 7.8 hours | Geometric Coefficient of Variation 48.6 |
| Group 2: Bexagliflozin Alone | T1/2 (Apparent Terminal Elimination Half-life) | Bexagliflozin PK parameters | 8.0 hours | Geometric Coefficient of Variation 33.3 |
| Group 2: Glimepiride Alone | T1/2 (Apparent Terminal Elimination Half-life) | Glimepiride PK parameters | 7.8 hours | Geometric Coefficient of Variation 46.8 |
| Group 2: Bexagliflozin + Glimepiride | T1/2 (Apparent Terminal Elimination Half-life) | Glimepiride PK parameters | 6.6 hours | Geometric Coefficient of Variation 57.8 |
| Group 2: Bexagliflozin + Glimepiride | T1/2 (Apparent Terminal Elimination Half-life) | Bexagliflozin PK parameters | 7.8 hours | Geometric Coefficient of Variation 34.4 |
| Group 3: Bexagliflozin Alone | T1/2 (Apparent Terminal Elimination Half-life) | Bexagliflozin PK parameters | 12.6 hours | Geometric Coefficient of Variation 48 |
| Group 3: Sitagliptin Alone | T1/2 (Apparent Terminal Elimination Half-life) | Sitagliptin PK parameters | 14.3 hours | Geometric Coefficient of Variation 22.3 |
| Group 3: Bexagliflozin + Sitagliptin | T1/2 (Apparent Terminal Elimination Half-life) | Bexagliflozin PK parameters | 13.3 hours | Geometric Coefficient of Variation 38.2 |
| Group 3: Bexagliflozin + Sitagliptin | T1/2 (Apparent Terminal Elimination Half-life) | Sitagliptin PK parameters | 14.8 hours | Geometric Coefficient of Variation 24.5 |
Primary
Tmax (Time of Maximum Observed Plasma Concentration)
Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Tmax was obtained directly from experimental observations.
Time frame: Up to 72 hours
Population: The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: Bexagliflozin Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 4.0 hours |
| Group 1: Metformin Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Metformin PK parameters | 2.5 hours |
| Group 1: Bexagliflozin + Metformin | Tmax (Time of Maximum Observed Plasma Concentration) | Metformin PK parameters | 2.0 hours |
| Group 1: Bexagliflozin + Metformin | Tmax (Time of Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 3.0 hours |
| Group 2: Bexagliflozin Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 8.0 hours |
| Group 2: Glimepiride Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Metformin PK parameters | 0 hours |
| Group 2: Glimepiride Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Glimepiride PK parameters | 5.5 hours |
| Group 2: Bexagliflozin + Glimepiride | Tmax (Time of Maximum Observed Plasma Concentration) | Glimepiride PK parameters | 7.0 hours |
| Group 2: Bexagliflozin + Glimepiride | Tmax (Time of Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 6.0 hours |
| Group 3: Bexagliflozin Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 3.0 hours |
| Group 3: Sitagliptin Alone | Tmax (Time of Maximum Observed Plasma Concentration) | Sitagliptin PK parameters | 2.5 hours |
| Group 3: Bexagliflozin + Sitagliptin | Tmax (Time of Maximum Observed Plasma Concentration) | Bexagliflozin PK parameters | 4.0 hours |
| Group 3: Bexagliflozin + Sitagliptin | Tmax (Time of Maximum Observed Plasma Concentration) | Sitagliptin PK parameters | 2.5 hours |
Secondary
Urinary Glucose Excretion up to 0-72 hr
Pre-dose urine samples were collected from -12 to 0 h for baseline measurement. Subjects was instructed to empty their bladder prior to dosing. Post-dose urine was collected in 4 batches for Groups 1 and 2 at 0 to 12 h, 12 to 24 h, 24 o 36 h, and 36 to 48 h collections. Post-dose urine was collected in batches for Group 3 at 0 to 12 h, 12 to 24 h, 24 to 36 h, 36 to 48 h, 48 to 60 h and 60 to 72 h.
Time frame: up to 0-72 hr
Population: Only subjects with data in the specific category is analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 23.94 g | Standard Deviation 9.16 |
| Group 1: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 17.32 g | Standard Deviation 11.81 |
| Group 1: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 8.91 g | Standard Deviation 4.97 |
| Group 1: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 31.57 g | Standard Deviation 8.06 |
| Group 1: Metformin Alone | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 0.02 g | Standard Deviation 0.01 |
| Group 1: Metformin Alone | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 0.04 g | Standard Deviation 0.04 |
| Group 1: Metformin Alone | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 0.04 g | Standard Deviation 0.03 |
| Group 1: Metformin Alone | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 0.02 g | Standard Deviation 0.01 |
| Group 1: Bexagliflozin + Metformin | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 22.57 g | Standard Deviation 8.29 |
| Group 1: Bexagliflozin + Metformin | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 26.26 g | Standard Deviation 8.86 |
| Group 1: Bexagliflozin + Metformin | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 19.50 g | Standard Deviation 8.94 |
| Group 1: Bexagliflozin + Metformin | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 5.53 g | Standard Deviation 4.17 |
| Group 2: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 36.99 g | Standard Deviation 14.24 |
| Group 2: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 26.85 g | Standard Deviation 9.51 |
| Group 2: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 11.03 g | Standard Deviation 7.84 |
| Group 2: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 29.79 g | Standard Deviation 10.24 |
| Group 2: Glimepiride Alone | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 0.04 g | Standard Deviation 0.05 |
| Group 2: Glimepiride Alone | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 0.20 g | Standard Deviation 0.42 |
| Group 2: Glimepiride Alone | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 1.26 g | Standard Deviation 4.37 |
| Group 2: Glimepiride Alone | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 0.03 g | Standard Deviation 0.01 |
| Group 2: Bexagliflozin + Glimepiride | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 22.59 g | Standard Deviation 11.15 |
| Group 2: Bexagliflozin + Glimepiride | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 28.46 g | Standard Deviation 11.37 |
| Group 2: Bexagliflozin + Glimepiride | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 9.34 g | Standard Deviation 7.55 |
| Group 2: Bexagliflozin + Glimepiride | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 31.02 g | Standard Deviation 11.19 |
| Group 3: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 48 - 60 hours | 11.32 g | Standard Deviation 8.09 |
| Group 3: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 29.01 g | Standard Deviation 6.84 |
| Group 3: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 24.38 g | Standard Deviation 7.92 |
| Group 3: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 22.31 g | Standard Deviation 8.97 |
| Group 3: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 9.83 g | Standard Deviation 6.67 |
| Group 3: Bexagliflozin Alone | Urinary Glucose Excretion up to 0-72 hr | 60 - 72 hours | 2.67 g | Standard Deviation 3.55 |
| Group 3: Sitagliptin Alone | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 0.17 g | Standard Deviation 0.56 |
| Group 3: Sitagliptin Alone | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 0.04 g | Standard Deviation 0.05 |
| Group 3: Sitagliptin Alone | Urinary Glucose Excretion up to 0-72 hr | 60 - 72 hours | 0.02 g | Standard Deviation 0.01 |
| Group 3: Sitagliptin Alone | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 0.03 g | Standard Deviation 0.01 |
| Group 3: Sitagliptin Alone | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 0.03 g | Standard Deviation 0.01 |
| Group 3: Sitagliptin Alone | Urinary Glucose Excretion up to 0-72 hr | 48 - 60 hours | 0.05 g | Standard Deviation 0.07 |
| Group 3: Bexagliflozin + Sitagliptin | Urinary Glucose Excretion up to 0-72 hr | 24 - 36 hours | 24.15 g | Standard Deviation 9.27 |
| Group 3: Bexagliflozin + Sitagliptin | Urinary Glucose Excretion up to 0-72 hr | 12 - 24 hours | 22.85 g | Standard Deviation 9.59 |
| Group 3: Bexagliflozin + Sitagliptin | Urinary Glucose Excretion up to 0-72 hr | 0 - 12 hours | 23.94 g | Standard Deviation 7.17 |
| Group 3: Bexagliflozin + Sitagliptin | Urinary Glucose Excretion up to 0-72 hr | 48 - 60 hours | 11.50 g | Standard Deviation 7.52 |
| Group 3: Bexagliflozin + Sitagliptin | Urinary Glucose Excretion up to 0-72 hr | 60 - 72 hours | 2.70 g | Standard Deviation 2.91 |
| Group 3: Bexagliflozin + Sitagliptin | Urinary Glucose Excretion up to 0-72 hr | 36 - 48 hours | 10.17 g | Standard Deviation 5.23 |