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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Cmax (Maximum Observed Plasma Concentration)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Bexagliflozin (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.
干预措施: Probenecid (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.
干预措施: 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.
干预措施: 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.
干预措施: 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.
干预措施: Verapamil (Drug)
结局指标
主要结局
Cmax (Maximum Observed Plasma Concentration)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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).
次要结局
- Urinary Glucose Excretion 0-48 hr(0 to 48 hours)