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 the heart failure medication digoxin. The study will evaluate whether bexagliflozin effects the amount of digoxin in your blood and how safe the study drug is and how well the study drug is tolerated when taken with digoxin.
Detailed description
This was a phase 1, single center, open-label, two-period, two-treatment, crossover study to evaluate the effect of bexagliflozin tablets, 20 mg, on the pharmacokinetics (PK) of digoxin, 0.5 mg after co-administration in healthy subjects. Each subject was randomized into one of 2 treatment groups and participated in 2 treatment periods as outlined below. During the duration of the study, each subject received 8 single doses of bexagliflozin and 2 single doses of digoxin. Clinical laboratory tests and safety monitoring were conducted during Periods 1 and 2. Group 1 - Period 1, Treatment A Subjects were admitted to the clinic on Day 0. Subjects received daily oral doses of a bexagliflozin tablet, 20 mg, starting on Day 1 for 8 days, and a single oral dose of 0.5 mg digoxin (two 0.25 mg tablets) was co-administered with bexagliflozin on Day 3. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (h) on Day 3, 24 h (Day 4), 48 h (Day 5), 72 h (Day 6), 96 h (Day 7), and 120 h (Day 8) after administration of digoxin. Subjects were discharged on Day 8. Group 1 - Period 2, Treatment B Subjects were admitted to the clinic on Day 18. On Day 19, subjects received a single oral dose of 0.5 mg digoxin. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h on Day 19, 24 h (Day 20), 48 h (Day 21), 72 h (Day 22), 96 h (Day 23), and 120 h (Day 24) after administration of digoxin. Subjects were discharged on Day 24. Group 2 - Period 1, Treatment B Subjects were admitted to the clinic on Day 0. On Day 1, subjects received a single oral dose of 0.5 mg digoxin. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h on Day 1, 24 h (Day 2), 48 h (Day 3), 72 h (Day 4), 96 h (Day 5), and 120 h (Day 6) after administration of digoxin. Subjects were discharged on Day 6. Group 2 - Period 2, Treatment A Subjects were admitted to the clinic on Day 14. Subjects received daily oral doses of a bexagliflozin tablet, 20 mg, for 8 days starting on Day 15, and a single oral dose of 0.5 mg digoxin (two 0.25 mg tablets) was co-administered with bexagliflozin on Day 17. Blood samples for PK were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h on Day 17, 24 h (Day 18), 48 h (Day 19), 72 h (Day 20), 96 h (Day 21), and 120 h (Day 22) after administration of digoxin. Subjects were discharged on Day 22.
Interventions
DRUGBexagliflozin
Bexagliflozin tablets, 20 mg
DRUGDigoxin
2 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin)
Sponsors
Theracos
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 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 6 months prior to first dose 3. Subjects who are willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic
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. Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer 5. Subjects who had previously received digoxin or drugs of the same class, or SGLT2 inhibitors, in the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Digoxin Cmax (Maximum Observed Plasma Concentration) | Up to 120 hours | Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin |
| Digoxin Tmax (Time of Maximum Observed Plasma Concentration) | Up to 120 hours | Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin |
| Digoxin T1/2 (Apparent Terminal Elimination Half-life) | Up to 120 hours | Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin |
| AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | Up to 120 hours | Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin |
Countries
United States
Participant flow
Pre-assignment details
In this crossover study, the subject was to participate in 2 periods during which subjects received 2 treatments (A: Bexagliflozin co-administered with digoxin, B: Digoxin alone).
Participants by arm
| Arm | Count |
|---|---|
| Bexagliflozin and Digoxin, Then Digoxin Alone Subjects received daily oral doses of a bexagliflozin tablet, 20 mg, starting on Day 1 for 8 days, and a single oral dose of 0.5 mg digoxin (two 0.25 mg tablets) was co-administered with bexagliflozin on Day 3 | 10 |
| Digoxin Alone, Then Bexagliflozin and Digoxin On Day 1, subjects received a single oral dose of 0.5 mg digoxin. Subjects received daily oral doses of a bexagliflozin tablet, 20 mg, for 8 days starting on Day 15, and a single oral dose of 0.5 mg digoxin (two 0.25 mg tablets) was co-administered with bexagliflozin on Day 17. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Bexagliflozin and Digoxin, Then Digoxin Alone | Digoxin Alone, Then Bexagliflozin and Digoxin | Total |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 8.84 | 35.2 years STANDARD_DEVIATION 6.37 | 40.0 years STANDARD_DEVIATION 8.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.1 cm STANDARD_DEVIATION 8.44 | 165.6 cm STANDARD_DEVIATION 9.35 | 166.4 cm STANDARD_DEVIATION 8.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
| Weight | 73.6 kg STANDARD_DEVIATION 11.28 | 74.2 kg STANDARD_DEVIATION 13.67 | 73.9 kg STANDARD_DEVIATION 12.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 3 / 20 | 5 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 |
Outcome results
Primary
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin
Time frame: Up to 120 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Alone | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | 35.558 h*ng/mL | Geometric Coefficient of Variation 16.6 |
| Digoxin With Bexagliflozin | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) | 37.805 h*ng/mL | Geometric Coefficient of Variation 27.5 |
Comparison: Geometric LS Mean was used as PK parameters90% CI: [95.82, 117.53]
Primary
Digoxin Cmax (Maximum Observed Plasma Concentration)
Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin
Time frame: Up to 120 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Alone | Digoxin Cmax (Maximum Observed Plasma Concentration) | 2.315 ng/mL | Geometric Coefficient of Variation 28.8 |
| Digoxin With Bexagliflozin | Digoxin Cmax (Maximum Observed Plasma Concentration) | 2.301 ng/mL | Geometric Coefficient of Variation 40.9 |
Comparison: Geometric LS Mean was used as PK parameters90% CI: [86.49, 116.56]
Primary
Digoxin T1/2 (Apparent Terminal Elimination Half-life)
Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin
Time frame: Up to 120 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Alone | Digoxin T1/2 (Apparent Terminal Elimination Half-life) | 34.3 hours | Geometric Coefficient of Variation 15.5 |
| Digoxin With Bexagliflozin | Digoxin T1/2 (Apparent Terminal Elimination Half-life) | 38.2 hours | Geometric Coefficient of Variation 15.7 |
Primary
Digoxin Tmax (Time of Maximum Observed Plasma Concentration)
Blood samples for pharmacokinetic parameters were drawn at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after administration of digoxin
Time frame: Up to 120 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Digoxin Alone | Digoxin Tmax (Time of Maximum Observed Plasma Concentration) | 1.00 hours |
| Digoxin With Bexagliflozin | Digoxin Tmax (Time of Maximum Observed Plasma Concentration) | 1.00 hours |