A Phase 1, Open-Label, Non-Randomized, Fixed-Sequence Composite Study to Evaluate the Effects of Probenecid, Rifampin, and Verapamil on the Pharmacokinetics and Pharmacodynamics of Bexagliflozin in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Cmax (Maximum Observed Plasma Concentration)
Study Overview
Brief Summary
The purpose of this study is to examine the drug-drug interaction when given the study drug, bexagliflozin, with three commonly prescribed medications, probenecid, verapamil or rifampin. The study is to evaluate how safe the study drug is and how well the study drug is tolerated when taken with probenecid, verapamil or rifampin.
Detailed Description
In this study, a total of 48 healthy subjects were enrolled and assigned to one of three groups of 16 subjects. Each group participated in an open-label, non-randomized, fixed-sequence studies to assess potential interaction of bexagliflozin tablets, 20 mg with probenecid, rifampin or verapamil.
Sequence 1: Bexagliflozin/probenecid Sixteen healthy subjects were dosed with bexagliflozin, qd and/or probenecid tablets, 500 mg, bid, in sequential order as follows: on Day 1 subjects took bexagliflozin; on Days 3 and 4 subjects took probenecid, bid; on Day 5 subjects took one bexagliflozin, and probenecid, bid; and on Day 6 subjects took probenecid tablets, 500 mg, bid.
Sequence 2: Bexagliflozin/rifampin Sixteen healthy subjects were dosed with bexagliflozin, qd and/or 600 mg of rifampin daily in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet; on Days 3 to 5, subjects took rifampin once daily; on Day 6 subjects took one bexagliflozin tablet and rifampin; and on Day 7 subjects took rifampin.
Sequence 3: Bexagliflozin/verapamil Sixteen healthy subjects were dosed with bexagliflozin, and/or verapamil tablets, 120 mg in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet, on Day 4 subjects took one verapamil tablet, 1 hour before taking a bexagliflozin tablet.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Bexagliflozin/rifampin
Sixteen healthy subjects were dosed with bexagliflozin, qd and/or 600 mg of rifampin daily in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet; on Days 3 to 5, subjects took rifampin once daily; on Day 6 subjects took one bexagliflozin tablet and rifampin; and on Day 7 subjects took rifampin.
Intervention: Bexagliflozin (Drug)
Bexagliflozin/rifampin
Sixteen healthy subjects were dosed with bexagliflozin, qd and/or 600 mg of rifampin daily in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet; on Days 3 to 5, subjects took rifampin once daily; on Day 6 subjects took one bexagliflozin tablet and rifampin; and on Day 7 subjects took rifampin.
Intervention: Rifampin (Drug)
Bexagliflozin/verapamil
Sixteen healthy subjects were dosed with bexagliflozin, and/or verapamil tablets, 120 mg in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet, on Day 4 subjects took one verapamil tablet, 1 hour before taking a bexagliflozin tablet.
Intervention: Bexagliflozin (Drug)
Bexagliflozin/verapamil
Sixteen healthy subjects were dosed with bexagliflozin, and/or verapamil tablets, 120 mg in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet, on Day 4 subjects took one verapamil tablet, 1 hour before taking a bexagliflozin tablet.
Intervention: Verapamil (Drug)
Bexagliflozin/probenecid
Sixteen healthy subjects were dosed with bexagliflozin, qd and/or probenecid tablets, 500 mg, bid, in sequential order as follows: on Day 1 subjects took bexagliflozin; on Days 3 and 4 subjects took probenecid, bid; on Day 5 subjects took one bexagliflozin, and probenecid, bid; and on Day 6 subjects took probenecid tablets, 500 mg, bid.
Intervention: Probenecid (Drug)
Bexagliflozin/probenecid
Sixteen healthy subjects were dosed with bexagliflozin, qd and/or probenecid tablets, 500 mg, bid, in sequential order as follows: on Day 1 subjects took bexagliflozin; on Days 3 and 4 subjects took probenecid, bid; on Day 5 subjects took one bexagliflozin, and probenecid, bid; and on Day 6 subjects took probenecid tablets, 500 mg, bid.
Intervention: Bexagliflozin (Drug)
Outcomes
Primary Outcomes
Cmax (Maximum Observed Plasma Concentration)
Time Frame: Up to 48 hours
Whole venous blood samples of 3 mL were collected from a peripheral vein prior to dosing and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin; On Day 1 and Day 5 for Study 1, Day 1 and Day 6 for Study 2, Day 1 and Day 4 for Study 3. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
T1/2 (Apparent Terminal Elimination Half-life)
Time Frame: Up to 48 hours
Whole venous blood samples of 3 mL were collected from a peripheral vein prior to dosing and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin; On Day 1 and Day 5 for Study 1, Day 1 and Day 6 for Study 2, Day 1 and Day 4 for Study 3. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Tmax (Time of Maximum Observed Plasma Concentration)
Time Frame: Up to 48 hours
Whole venous blood samples of 3 mL were collected from a peripheral vein prior to dosing and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin; On Day 1 and Day 5 for Study 1, Day 1 and Day 6 for Study 2, Day 1 and Day 4 for Study 3. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Time Frame: Up to 48 hours
Whole venous blood samples of 3 mL were collected from a peripheral vein prior to dosing and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h after administration of bexagliflozin; On Day 1 and Day 5 for Study 1, Day 1 and Day 6 for Study 2, Day 1 and Day 4 for Study 3. The pharmacokinetic parameters were estimated from the bexagliflozin plasma concentration data for each subject by non-compartmental analysis (NCA).
Secondary Outcomes
- Urinary Glucose Excretion 0-48 hr(0 to 48 hours)