Clinical trial NCT03197324: Bexagliflozin Drug/Drug Interaction Study With Digoxin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type2 Diabetes Mellitus
Lead sponsor: Theracos
Sponsor class: INDUSTRY
First posted: 2017-06-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Digoxin Cmax (Maximum Observed Plasma Concentration)
timeFrame: Up to 120 hours
measure: Digoxin Tmax (Time of Maximum Observed Plasma Concentration)
timeFrame: Up to 120 hours
measure: Digoxin T1/2 (Apparent Terminal Elimination Half-life)
timeFrame: Up to 120 hours
measure: AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
timeFrame: Up to 120 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance CRU
state: Florida
Study officials:
affiliation: Massachusetts General Hospital
name: Mason Freeman, M.D.
role: STUDY_DIRECTOR
References: