Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 500 mg Metformin Immediate Release (IR) Tablet Relative to 2.5 mg Saxagliptin Tablet and 500 mg Metformin IR Tablet Co-administered to Healthy Subjects in a Fasted and in a Fed State
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])
研究概览
简要总结
To demonstrate bioequivalence of a 2.5 mg saxagliptin/500 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 500 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women ages 19 to 45 inclusive
- •Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
- •Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2
排除标准
- •Women of child-bearing potential (WOCBP) who are unwilling or unable to use acceptable barrier methods (condoms and spermicides) to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product
- •Any significant acute or chronic medical illness
- •Current or recent (within 3 months) gastrointestinal disease
- •Any major surgery within 4 weeks of study drug administration
- •History of allergy to Dipeptidyl peptidase 4 (DPP4) inhibitor or related compounds
- •History of allergy or intolerance to metformin or other similar acting agents
- •Prior exposure to saxagliptin
- •Prior exposure to metformin within 3 months of study drug administration.
- •Estimated creatinine clearance (Clcr) of < 80ml/min using the Cockcroft Gault formula
研究组 & 干预措施
S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)
Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M [fasted]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M [fed]) followed by S/M under fasting conditions (S/M [fasted]) followed by S + M under fed conditions (S + M [fed])
干预措施: Co-administration of Saxagliptin and Metformin IR, Fasted (Drug)
S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)
Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M [fasted]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M [fed]) followed by S/M under fasting conditions (S/M [fasted]) followed by S + M under fed conditions (S + M [fed])
干预措施: Saxagliptin/Metformin, Fasting (Drug)
S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)
Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M [fasted]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M [fed]) followed by S/M under fasting conditions (S/M [fasted]) followed by S + M under fed conditions (S + M [fed])
干预措施: Co-administration of Saxagliptin and Metformin IR, Fed (Drug)
S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)
Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M [fasted]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M [fed]) followed by S/M under fasting conditions (S/M [fasted]) followed by S + M under fed conditions (S + M [fed])
干预措施: Saxagliptin/Metformin, Fed (Drug)
S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)
Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)
干预措施: Co-administration of Saxagliptin and Metformin IR, Fasted (Drug)
S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)
Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)
干预措施: Saxagliptin/Metformin, Fasting (Drug)
S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)
Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)
干预措施: Co-administration of Saxagliptin and Metformin IR, Fed (Drug)
S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)
Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)
干预措施: Saxagliptin/Metformin, Fed (Drug)
S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)
Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)
干预措施: Co-administration of Saxagliptin and Metformin IR, Fasted (Drug)
S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)
Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)
干预措施: Saxagliptin/Metformin, Fasting (Drug)
S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)
Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)
干预措施: Co-administration of Saxagliptin and Metformin IR, Fed (Drug)
S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)
Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)
干预措施: Saxagliptin/Metformin, Fed (Drug)
S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)
干预措施: Co-administration of Saxagliptin and Metformin IR, Fasted (Drug)
S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)
干预措施: Saxagliptin/Metformin, Fasting (Drug)
S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)
干预措施: Co-administration of Saxagliptin and Metformin IR, Fed (Drug)
S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)
干预措施: Saxagliptin/Metformin, Fed (Drug)
结局指标
主要结局
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin Mean AUC (0-T)
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
AUC (0-T for single-dose metformin (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin T-half and T-max
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
T-half and T-max for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg), or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Cmax of single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max)
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
T-half and T-max for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg) or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin Mean Cmax
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Cmax of single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin Mean AUC(0-INF)
时间窗: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
AUC (0-INF) for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
次要结局
- BMS-510849 Mean T-half and T-max(Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr)
- BMS-510849 Mean AUC (0-T)(Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr)
- BMS-510849 Mean Cmax(Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr)
- Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities(Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3)
- Number of Participants With Clinically Relevant Vital Sign Abnormalities(Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3)
- BMS-510849 Mean AUC (0-INF)(Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr)
- Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation(From Day 1 through Day 45, including up to 56 days after last dose of study medication)
- Number of Participants With Laboratory Marked Abnormalities(From Day 1 through Day 45, including up to 56 days after last dose of study medication)
- Number of Participant With Clinically Relevant Physical Examination Abnormalities(Screen, Period 1 Day -1, prior to discharge)