A Phase 1, 2-part, Open-label, Fixed-sequence Study Evaluating Potential Drug-drug Interactions Between Gemfibrozil (Part 1) or Dabigatran Etexilate (Part 2) and Camlipixant (BLU-5937) 50 mg Tablet in Healthy Participants Under Fasting Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) of Camlipixant
研究概览
简要总结
This is a phase 1, 2-part, open-label, fixed-sequence study evaluating potential drug-drug interactions between gemfibrozil (part 1) or dabigatran etexilate (part 2) and camlipixant (BLU-5937) 50 mg tablet in healthy participants under fasting conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Healthy males or non-pregnant, non-lactating healthy females
排除标准
- •History of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disorder, as judged by the investigator.
研究组 & 干预措施
Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg
Participants received a single oral dose of camlipixant 50 milligram (mg) tablet on Day 1, followed by repeat oral doses of gemfibrozil 600 mg tablet twice daily (BID), every 12 hours, (total daily dose of 1200 mg) on Days 5 to 11, with co-administration of a single oral dose of camlipixant 50 mg tablet with the gemfibrozil on Day 9. There was a washout of at least 4 days between the dose of camlipixant on Day 1 and the dose of gemfibrozil on Day 5.
干预措施: Camlipixant (Drug)
Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg
Participants received a single oral dose of camlipixant 50 milligram (mg) tablet on Day 1, followed by repeat oral doses of gemfibrozil 600 mg tablet twice daily (BID), every 12 hours, (total daily dose of 1200 mg) on Days 5 to 11, with co-administration of a single oral dose of camlipixant 50 mg tablet with the gemfibrozil on Day 9. There was a washout of at least 4 days between the dose of camlipixant on Day 1 and the dose of gemfibrozil on Day 5.
干预措施: Gemfibrozil (Drug)
Part 2: Dabigatran etexilate 150 mg + camlipixant 50 mg
Participants received single oral dose of dabigatran etexilate 150 mg capsule on Day 1, followed by repeated oral doses of camlipixant 50 mg tablet twice daily (BID) (total daily dose of 100 mg) from Days 5 to 9, with co-administration of a single oral dose of dabigatran etexilate 150 mg capsule with the morning dose of camlipixant on Day 10. There was a washout of at least 4 days between the dose of dabigatran etexilate on Day 1 and the dose of camlipixant on Day 5.
干预措施: Camlipixant (Drug)
Part 2: Dabigatran etexilate 150 mg + camlipixant 50 mg
Participants received single oral dose of dabigatran etexilate 150 mg capsule on Day 1, followed by repeated oral doses of camlipixant 50 mg tablet twice daily (BID) (total daily dose of 100 mg) from Days 5 to 9, with co-administration of a single oral dose of dabigatran etexilate 150 mg capsule with the morning dose of camlipixant on Day 10. There was a washout of at least 4 days between the dose of dabigatran etexilate on Day 1 and the dose of camlipixant on Day 5.
干预措施: Dabigatran etexilate (Drug)
结局指标
主要结局
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) of Camlipixant
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Maximal Observed Concentration (Cmax) of Camlipixant
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: AUC(0-t) of Free Dabigatran
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Part 2: AUC(0-Infinity) of Free Dabigatran
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Part 2: Cmax of Free Dabigatran
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Part 2: AUC(0-Infinity) of Total Dabigatran
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Part 2: AUC(0-t) of Total Dabigatran
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Part 2: Cmax of Total Dabigatran
时间窗: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
次要结局
- Part 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9)
- Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9)
- Part 1: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Camlipixant(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9)
- Part 1: Terminal Elimination Rate Constant of Camlipixant (Kel)(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9)
- Part 1: Apparent Clearance (CL/F) of Camlipixant(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9)
- Part 1: Apparent Volume of Distribution (Vz/F) of Camlipixant(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9)
- Part 2: Tmax of Free Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: T1/2 Following Administration Free Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Free Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Kel Free Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: CL/F Free Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Vz/F Free Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Tmax of Total Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: T1/2 Following Administration of Total Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Total Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Kel of Total Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: CL/F of Total Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 2: Vz/F of Total Dabigatran(Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10)
- Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Treatment-emergent Adverse Events of Medical Interest (TEAEMIs)(Day 1 post-dose until Day 5 pre-dose of gemfibrozil [camlipixant 50mg]; from Day 5 dosing until Day 9 pre-dose of camlipixant [gemfibrozil 600mg]; from camlipixant dosing on Day 9 until end of study [Day 21] [camlipixant 50mg+gemfibrozil 600mg])
- Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs(Day1 postdose until Day5 predose of camlipixant [dabigatran etexilate 150mg];from Day5 dosing until Day10 predose of dabigatran [camlipixant 50mg];from dabigatran dosing on Day10 until end of study [Day 22][dabigatran etexilate 150mg+camlipixant 50mg])
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings(Day 5, Day 9 pre-dose and 1 hour post-dose, Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings(Day 5, Day 10 and Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), and Heart Rate(Day 9 and Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate(Day 10 and Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature(Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature(Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes During Physical Examination(Up to Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes During Physical Examination(Up to Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters(Up to Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters(Up to Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters(Up to Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters(Up to Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters(Up to Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters(Up to Day 13)
- Part 1: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis(Up to Day 12)
- Part 2: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis(Up to Day 13)