A Phase 1, Open-label, Randomized, Three-period, Crossover Study to Evaluate Pharmacokinetic Interaction Between Bexagliflozin Tablets and Metformin, Glimepiride, or Sitagliptin in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Tmax (Time of Maximum Observed Plasma Concentration)
研究概览
简要总结
The purpose of this study is to examine the drug-drug interaction in your body when given the study drug, bexagliflozin, with three commonly used ant-diabetic medications, metformin, glimepiride or sitagliptin. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when taken with metformin, glimepiride or sitagliptin.
详细描述
A total of 54 healthy subjects were enrolled and assigned to one of three groups of eighteen. Each group participated in one of three open-label, randomized, three treatment period, crossover studies:
- Group 1: Bexagliflozin/metformin drug-drug interaction (DDI)
- Group 2: Bexagliflozin/glimepiride DDI
- Group 3: Bexagliflozin/sitagliptin DDI For each Group, every subject received a single dose of bexagliflozin tablet, 20 mg, alone, a single dose of an oral hypoglycemic agent (OHA) (1000 mg metformin, 2 mg glimepiride, or 100 mg sitagliptin) alone, and the combination of both (bexagliflozin tablet and OHA) alternately in a crossover fashion, with three treatment periods separated by a washout period of at least 7 days. Within each Group, subjects were randomized to one of six treatment sequences in an equal ratio.
To prevent hypoglycemia, subjects assigned to Group 2 (bexagliflozin/glimepiride DDI) received approximately 300 mL of a solution containing 50 g of glucose with study medication at the time of dosing, as well as approximately 75 mL of a solution containing 12.5 g of glucose every 15 minutes for 4 hours post-dose.
For each treatment period in Group 1 (bexagliflozin/metformin DDI) and Group 2 (bexagliflozin/glimepiride DDI), subjects were admitted to the clinic on the day before dosing and stayed in the clinic until 48 h post-dose. For Group 3 (bexagliflozin/sitagliptin DDI), subjects stayed in the clinic until 72 h post-dose.
For all Groups, blood samples for PK analysis were collected in each period prior to dosing (pre-dose) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose. For Group 3, PK blood samples were also collected at 60 and 72 h post-dose. Plasma concentrations of bexagliflozin and OHAs were determined by validated liquid chromatography tandem mass spectrometry (LC MS/MS) assays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2
- •Subjects who are non-smokers for at least 3 months prior to screening
- •Subjects who are willing and able to be confined to the clinical research facility as required by the protocol
排除标准
- •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
- •Female subjects who are pregnant or breastfeeding
- •Subjects who are not willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic
- •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 anti-diabetic medication, including metformin, sitagliptin, glimepiride or drugs of the same class (i.e. biguanides, DPP-4 inhibitors or sulfonylureas), or SGLT2 inhibitors, in the past 3 months
研究组 & 干预措施
Group 1: Metformin alone
干预措施: Metformin (Drug)
Group 1: Bexagliflozin + Metformin
干预措施: Bexagliflozin (Drug)
Group 1: Bexagliflozin + Metformin
干预措施: Metformin (Drug)
Group 1: Bexagliflozin alone
干预措施: Bexagliflozin (Drug)
Group 2: Bexagliflozin alone
干预措施: Bexagliflozin (Drug)
Group 2: Glimepiride alone
干预措施: Glimepiride (Drug)
Group 2: Bexagliflozin + Glimepiride
干预措施: Bexagliflozin (Drug)
Group 2: Bexagliflozin + Glimepiride
干预措施: Glimepiride (Drug)
Group 3: Bexagliflozin alone
干预措施: Bexagliflozin (Drug)
Group 3: Sitagliptin alone
干预措施: Sitagliptin (Drug)
Group 3: Bexagliflozin + Sitagliptin
干预措施: Bexagliflozin (Drug)
Group 3: Bexagliflozin + Sitagliptin
干预措施: Sitagliptin (Drug)
结局指标
主要结局
Tmax (Time of Maximum Observed Plasma Concentration)
时间窗: Up to 72 hours
Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Tmax was obtained directly from experimental observations.
Cmax (Maximum Observed Plasma Concentration)
时间窗: Up to 72 hours
Whole venous blood samples of 5 mL were be collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. Pharmacokinetic (PK) blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Cmax was obtained directly from experimental observations.
T1/2 (Apparent Terminal Elimination Half-life)
时间窗: Up to 72 hours
Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. T1/2 was obtained directly from experimental observations.
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
时间窗: Up to 72 hours
Whole venous blood samples of 5 mL were collected from a peripheral vein in each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. AUC0-inf was estimated for each subject.
次要结局
- Urinary Glucose Excretion up to 0-72 hr(up to 0-72 hr)