Bexagliflozin Drug/Drug Interaction Study With Digoxin
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Digoxin Alone first, then Digoxin With Bexagliflozin
|
Drug: Digoxin
2 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin)
|
Active Comparator: Digoxin with Bexagliflozin, then Digoxin alone
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
Other Names:
Drug: Digoxin
2 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin)
|
Outcome Measures
Primary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2
-
Subjects who are non-smokers for at least 6 months prior to first dose
-
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:
-
Subjects with a clinically significant history of allergy to drugs or latex
-
Subjects with a history of alcohol or drug dependence in the past 12 months
-
Subjects who have donated a significant amount of blood in the past 2 months
-
Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer
-
Subjects who had previously received digoxin or drugs of the same class, or SGLT2 inhibitors, in the past 3 months
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Covance CRU | Daytona Beach | Florida | United States | 32117 |
Sponsors and Collaborators
- Theracos
Investigators
- Study Director: Mason Freeman, M.D., Massachusetts General Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.- THR-1442-C-443
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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). |
Arm/Group Title | Digoxin and Bexagliflozin Tablet, Then Digoxin Alone | Digoxin, Then Digoxin and Bexagliflozin |
---|---|---|
Arm/Group Description | 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. Subjects were discharged on Day 8. On Day 19, subjects received a single oral dose of 0.5 mg digoxin and were discharged on Day 22. | On Day 1, subjects received a single oral dose of 0.5 mg digoxin. Subjects were discharged on Day 6. 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. Subjects were discharged on Day 22. |
Period Title: Overall Study | ||
STARTED | 10 | 10 |
COMPLETED | 10 | 9 |
NOT COMPLETED | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Bexagliflozin and Digoxin, Then Digoxin Alone | Digoxin Alone, Then Bexagliflozin and Digoxin | Total |
---|---|---|---|
Arm/Group Description | 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 | 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. | Total of all reporting groups |
Overall Participants | 10 | 10 | 20 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
44.8
(8.84)
|
35.2
(6.37)
|
40.0
(8.97)
|
Sex: Female, Male (Count of Participants) | |||
Female |
5
50%
|
5
50%
|
10
50%
|
Male |
5
50%
|
5
50%
|
10
50%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
5
50%
|
7
70%
|
12
60%
|
Not Hispanic or Latino |
5
50%
|
3
30%
|
8
40%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
1
10%
|
1
5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
4
40%
|
2
20%
|
6
30%
|
White |
6
60%
|
7
70%
|
13
65%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Weight (kg) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kg] |
73.6
(11.28)
|
74.2
(13.67)
|
73.9
(12.20)
|
Height (cm) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [cm] |
167.1
(8.44)
|
165.6
(9.35)
|
166.4
(8.71)
|
Outcome Measures
Title | Digoxin Cmax (Maximum Observed Plasma Concentration) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Digoxin Alone | Digoxin With Bexagliflozin |
---|---|---|
Arm/Group Description | Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) | Bexagliflozin: Bexagliflozin tablets, 20 mg Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) |
Measure Participants | 20 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
2.315
(28.8)
|
2.301
(40.9)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Digoxin Alone, Digoxin With Bexagliflozin |
---|---|---|
Comments | Geometric LS Mean was used as PK parameters | |
Type of Statistical Test | Equivalence | |
Comments | The acceptance range for bioequivalence is 80.0 - 125.00%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
Estimated Value | 100.40 | |
Confidence Interval |
(2-Sided) 90% 86.49 to 116.56 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Digoxin group is the denominator and Digoxin with Bexagliflozin is the numerator. Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subjects as a random effect. |
Title | Digoxin Tmax (Time of Maximum Observed Plasma Concentration) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Digoxin Alone | Digoxin With Bexagliflozin |
---|---|---|
Arm/Group Description | Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) | Bexagliflozin: Bexagliflozin tablets, 20 mg Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) |
Measure Participants | 20 | 19 |
Median (Full Range) [hours] |
1.00
|
1.00
|
Title | Digoxin T1/2 (Apparent Terminal Elimination Half-life) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Digoxin Alone | Digoxin With Bexagliflozin |
---|---|---|
Arm/Group Description | Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) | Bexagliflozin: Bexagliflozin tablets, 20 mg Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) |
Measure Participants | 18 | 18 |
Geometric Mean (Geometric Coefficient of Variation) [hours] |
34.3
(15.5)
|
38.2
(15.7)
|
Title | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Digoxin Alone | Digoxin With Bexagliflozin |
---|---|---|
Arm/Group Description | Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) | Bexagliflozin: Bexagliflozin tablets, 20 mg Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) |
Measure Participants | 18 | 18 |
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL] |
35.558
(16.6)
|
37.805
(27.5)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Digoxin Alone, Digoxin With Bexagliflozin |
---|---|---|
Comments | Geometric LS Mean was used as PK parameters | |
Type of Statistical Test | Superiority | |
Comments | Compare if co-administration of digoxin with bexagliflozin had significant impact on the PK of digoxin | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
Estimated Value | 106.12 | |
Confidence Interval |
(2-Sided) 90% 95.82 to 117.53 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Digoxin group is the denominator and Digoxin with Bexagliflozin is the numerator. Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subjects as a random effect. |
Adverse Events
Time Frame | Adverse event data were collected from Day 0 up to Day 24 of the study | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Digoxin Alone | Digoxin With Bexagliflozin | ||
Arm/Group Description | Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) | Bexagliflozin: Bexagliflozin tablets, 20 mg Digoxin: Two 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin) | ||
All Cause Mortality |
||||
Digoxin Alone | Digoxin With Bexagliflozin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 0/19 (0%) | ||
Serious Adverse Events |
||||
Digoxin Alone | Digoxin With Bexagliflozin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 0/19 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Digoxin Alone | Digoxin With Bexagliflozin | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/20 (15%) | 5/19 (26.3%) | ||
Cardiac disorders | ||||
Palpitations | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Eye disorders | ||||
Vision blurred | 1/20 (5%) | 1 | 0/19 (0%) | 0 |
Gastrointestinal disorders | ||||
Nausea | 1/20 (5%) | 1 | 1/19 (5.3%) | 1 |
General disorders | ||||
Fatigue | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Medical device site reaction | 1/20 (5%) | 1 | 0/19 (0%) | 0 |
Infections and infestations | ||||
Upper respiratory tract infection | 1/20 (5%) | 1 | 1/19 (5.3%) | 1 |
Urinary tract infection | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Injury, poisoning and procedural complications | ||||
Excoriation | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Metabolism and nutrition disorders | ||||
Hypoglycemia | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Nervous system disorders | ||||
Dizziness | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
PI does not have the right to publish trial results.
Results Point of Contact
Name/Title | Albert Collinson, Ph.D. |
---|---|
Organization | Theracos Sub, LLC |
Phone | 508-688-4221 |
acollinson@theracos.com |
- THR-1442-C-443