A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Debio 1450 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Number of participants with clinically significant change from baseline in safety parameters
研究概览
简要总结
Debio 1450-103 is a trial to study the pharmacokinetics (PK) of an experimental drug called Debio 1450 in healthy adult volunteers. Originally, Part A was registered separately (in NCT02214355). The registrations have been revised so all parts of this single trial (Parts A-C) are now included in this single registration (NCT02214433).
The primary purpose of each part is provided below:
- 10 volunteers participate in PART A to assess the PK of a single oral dose of Debio 1450 (tablet formulation) under varying gastric conditions
- 40 volunteers participate in PART B to assess the safety, tolerability and PK of multiple ascending doses of Debio 1450, administered sequentially IV and orally, once or twice daily.
- An additional 10 volunteers participate in PART C which is designed to assess the absolute bioavailability of various formulations of Debio 1450 under varying gastric conditions
The dose administered during Part A is based on the safety, tolerability and PK data from study Debio 1450-102 [NCT02162199], a single ascending dose (SAD) study, in which single oral doses up to 800 mg/day are being investigated. Doses are adjusted during Parts B and C based on the available safety and PK data from preceding cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
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
- •Meets protocol-specified criteria for qualification and/or contraception
- •Is willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related to food, drink and medications
- •Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures
排除标准
- •Has a history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
- •Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:
- •the safety or well-being of the participant or study staff
- •the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
- •the analysis of results
研究组 & 干预措施
Part A Period 1 Debio 1450 IV Solution
Part A Debio 1450 IV solution infused over two hours on Day 1 after fasting
干预措施: Debio 1450 IV Solution (Drug)
Part A Period 2 Debio 1450 Tablet
Debio 1450 Tablet oral dosing once on Day 5, after fasting
干预措施: Debio 1450 Tablet (Drug)
Part A Period 3 Debio 1450 Tablet
Debio 1450 Tablet oral dosing once on Day 9, 30 minutes after a high calorie, high fat breakfast, after fasting
干预措施: Debio 1450 Tablet (Drug)
Part A Period 4 Debio 1450 Tablet
After preparation with Pantoprazole, Pantoprazole taken with Debio 1450 Tablet oral dosing once on Day 14, after fasting
干预措施: Debio 1450 Tablet (Drug)
Part A Period 4 Debio 1450 Tablet
After preparation with Pantoprazole, Pantoprazole taken with Debio 1450 Tablet oral dosing once on Day 14, after fasting
干预措施: Pantoprazole (Drug)
Part B Placebo All Cohorts
Placebo IV solution on days 1-5 and then Placebo Tablet or Capsule on Days 6-10, according to the cohort dosing schedule
干预措施: Placebo IV Solution (Drug)
Part B Placebo All Cohorts
Placebo IV solution on days 1-5 and then Placebo Tablet or Capsule on Days 6-10, according to the cohort dosing schedule
干预措施: Placebo Tablet or Capsule (Drug)
Part B Debio 1450 Cohort 1
Debio 1450 IV solution, once daily on days 1-5, then Debio 1450 Tablet, once daily on days 6-10
干预措施: Debio 1450 IV Solution (Drug)
Part B Debio 1450 Cohort 1
Debio 1450 IV solution, once daily on days 1-5, then Debio 1450 Tablet, once daily on days 6-10
干预措施: Debio 1450 Tablet (Drug)
Part B Debio 1450 Cohort 2a
Debio 1450 IV solution, once daily on day 1
干预措施: Debio 1450 IV Solution (Drug)
Part B Debio 1450 Cohort 3
Debio 1450 IV solution, twice daily on days 1-5, then Debio 1450 Capsule, twice daily on days 6-10
干预措施: Debio 1450 IV Solution (Drug)
Part B Debio 1450 Cohort 3
Debio 1450 IV solution, twice daily on days 1-5, then Debio 1450 Capsule, twice daily on days 6-10
干预措施: Debio 1450 Capsule (Drug)
Part B Debio 1450 Cohort 4
Debio 1450 IV solution, twice daily on days 1-5, then Debio 1450 Capsule, twice daily on days 6-10
干预措施: Debio 1450 IV Solution (Drug)
Part B Debio 1450 Cohort 4
Debio 1450 IV solution, twice daily on days 1-5, then Debio 1450 Capsule, twice daily on days 6-10
干预措施: Debio 1450 Capsule (Drug)
Part B Debio 1450 Cohort 2b
Debio 1450 IV solution, once daily on days 1-5, then Debio 1450 Capsule, once daily on days 6-10
干预措施: Debio 1450 IV Solution (Drug)
Part B Debio 1450 Cohort 2b
Debio 1450 IV solution, once daily on days 1-5, then Debio 1450 Capsule, once daily on days 6-10
干预措施: Debio 1450 Capsule (Drug)
Part C Debio 1450
Debio 1450 (IV formulation in Period 1, capsule formulation in Periods 2, 4 and 5 (with Pantoprazole), and Debio 1450 oral solution in Period 3).
干预措施: Debio 1450 IV Solution (Drug)
Part C Debio 1450
Debio 1450 (IV formulation in Period 1, capsule formulation in Periods 2, 4 and 5 (with Pantoprazole), and Debio 1450 oral solution in Period 3).
干预措施: Debio 1450 Capsule (Drug)
Part C Debio 1450
Debio 1450 (IV formulation in Period 1, capsule formulation in Periods 2, 4 and 5 (with Pantoprazole), and Debio 1450 oral solution in Period 3).
干预措施: Debio 1450 Oral Solution (Drug)
Part C Debio 1450
Debio 1450 (IV formulation in Period 1, capsule formulation in Periods 2, 4 and 5 (with Pantoprazole), and Debio 1450 oral solution in Period 3).
干预措施: Pantoprazole (Drug)
结局指标
主要结局
Number of participants with clinically significant change from baseline in safety parameters
时间窗: within 10 days post-dose
Categories: vital signs, 12-lead electrocardiogram (ECG), clinical laboratory parameters, adverse events, pulmonary function, physical examination, concomitant medication
Maximum observed plasma concentration (Cmax) of Debio 1450 (prodrug) and Debio 1452 (active moiety)
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Time of maximum observed plasma concentration (tmax) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Area under the plasma concentration-time curve (AUC) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Percentage of AUC(0-o) that is due to extrapolation beyond the last quantifiable concentration measurement (%AUCex) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Elimination half-life (t1/2) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Terminal elimination rate constant (Az) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Mean residence time (MRT) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Apparent clearance following oral administration (CL/F) of Debio 1450 and Debio 1452
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Apparent volume of distribution of Debio 1450 and Debio 1452 during terminal phase (Vz/F)
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae)
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Renal clearance following oral administration
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
Percentage of cumulative amount of unchanged Debio 1450 and Debio 1452 excreted in urine (Ae%)
时间窗: within 60 hours post-dose, depending on the assessment schedule for the cohort
Categories: Placebo Tablet or Capsule, Placebo IV Solution, Debio 1450 IV solution, Debio 1450 Tablet, Debio 1450 Capsule, Debio 1450 oral solution
次要结局
未报告次要终点