Bexagliflozin Drug/Drug Interaction Study With Digoxin

Type2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effect of Bexagliflozin on the Pharmacokinetics of Digoxin in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03197324
• Other study ID #: THR-1442-C-443
• Status: Completed
• Phase: Phase 1
• Start date: July 24, 2017
• Est. completion date: September 17, 2017

Study information

• Verified date: July 2021
• Source: Theracos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 17, 2017
• Est. primary completion date: September 17, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Drug:
• Bexagliflozin
Bexagliflozin tablets, 20 mg
• Digoxin
2 0.25 mg Digoxin tablets (total dose 0.5 mg digoxin)

Locations

Country	Name	City	State
United States	Covance CRU	Daytona Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Up to 120 hours
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	Up to 120 hours
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	Up to 120 hours
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	Up to 120 hours