A Randomized, Open-Label, Single Dose, Four-Period Crossover Clinical Trial to Assess the Relative Bioavailability of a Tablet Compared to a Capsule of GSK3640254 and to Assess the Effect of Food on the GSK3640254 Tablet in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
研究概览
简要总结
This is an open-label, single-dose, four-period, four sequential, and crossover study conducted to assess the relative bioavailability of GSK3640254 mesylate tablets and GSK3640254 mesylate capsules (in the presence of a moderate fat meal). This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of GSK3640254 mesylate tablet formulation. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 16 participants will be enrolled and the duration of the study will be approximately 54 days.
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
盲法说明
This is an open-label study.
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
Sequence 1 - Treatment ABCD
Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Tablet (Drug)
Sequence 1 - Treatment ABCD
Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Capsule (Drug)
Sequence 2 - Treatment BADC
Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Tablet (Drug)
Sequence 2 - Treatment BADC
Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Capsule (Drug)
Sequence 3 - Treatment CDAB
Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Tablet (Drug)
Sequence 3 - Treatment CDAB
Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Capsule (Drug)
Sequence 4 - Treatment DCBA
Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Tablet (Drug)
Sequence 4 - Treatment DCBA
Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention.
干预措施: GSK3640254 Capsule (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.
AUC(0-infinity) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Maximum Observed Concentration (Cmax) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time of Cmax (Tmax) for GSK3640254 200 mg Tablets Under Fed, Fasted and High Fat Condition (Treatment B, C and D)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
AUC(0-t) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time of Cmax (Tmax) for GSK3640254 200 mg Capsules Under Fed Condition (Treatment A)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Cmax for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)
时间窗: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
次要结局
- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Day 14)
- Absolute Values for Hematology Parameter: Hematocrit(Day 2)
- Absolute Values for Body Temperature(Days 2, 3, 4, and 5)
- Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin(Baseline (Day -1) and at Day 2)
- Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Day 2)
- Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count(Day 2)
- Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase(Day 2)
- Absolute Values for Hematology Parameter: Erythrocytes(Day 2)
- Absolute Values for Hematology Parameter: Hemoglobin(Day 2)
- Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen(Day 2)
- Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin(Day 2)
- Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein(Day 2)
- Absolute Values for Urine Parameter: Specific Gravity(Day 2)
- Absolute Values for Urine Parameter: Urobilinogen(Day 2)
- Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF), Corrected QT Interval Using Bazett's Formula (QTcB)(Day 1: 2 hours and 4 hours)
- Change From Baseline in Hematology Parameter: Erythrocytes(Baseline (Day -1) and at Day 2)
- Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein(Baseline (Day -1) and at Day 2)
- Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB(Baseline (Day 1, Pre-dose), Day 1: 2 hours and 4 hours)
- Change From Baseline in Pulse Rate(Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5)
- Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Day 2)
- Absolute Values for Chemistry Parameters: Amylase, Lipase(Day 2)
- Absolute Values for Pulse Rate(Days 2, 3, 4, and 5)
- Change From Baseline in Hematology Parameter: Hemoglobin(Baseline (Day -1) and at Day 2)
- Change From Baseline in Hematology Parameter: Hematocrit(Baseline (Day -1) and at Day 2)
- Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase(Baseline (Day -1) and at Day 2)
- Change From Baseline in Respiratory Rate(Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5)
- Absolute Values for Urine Parameter: Potential of Hydrogen (pH)(Day 2)
- Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Days 2, 3, 4, and 5)
- Absolute Values for Respiratory Rate(Days 2, 3, 4, and 5)
- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count(Baseline (Day -1) and at Day 2)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Baseline (Day -1) and at Day 2)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Baseline (Day -1) and at Day 2)
- Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen(Baseline (Day -1) and at Day 2)
- Change From Baseline in Chemistry Parameters: Amylase, Lipase(Baseline (Day -1) and at Day 2)
- Change From Baseline in Urinalysis Parameter: Urobilinogen(Baseline (Day -1) and at Day 2)
- Change From Baseline in Body Temperature(Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5)
- Change From Baseline in Urinalysis Parameter: Specific Gravity(Baseline (Day -1) and at Day 2)
- Change From Baseline in Urinalysis Parameter: pH(Baseline (Day -1) and at Day 2)
- Plasma Pharmacokinetic Concentration of GSK3640254(Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Change From Baseline in SBP and DBP(Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5)
- Lag Time for Absorption (Tlag) for GSK3640254(Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Apparent Terminal Phase Half-life (t1/2) for GSK3640254(Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Apparent Oral Clearance (CL/F) for GSK3640254(Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Apparent Volume of Distribution (Vz/F) for GSK3640254(Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)