A Phase 1, Multiple Ascending Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fentanyl Sublingual Spray in Opioid Naive Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Dose normalized AUC
研究概览
简要总结
The primary objective of this trial is to determine the pharmacokinetic and pharmacodynamic relationship of multiple dose administration of fentanyl sublingual spray in opioid naive participants. The secondary objective is to determine the safety and tolerability of multiple dose administration of fentanyl sublingual spray in opioid naive subjects.
详细描述
For all cycles, blood will be drawn according to the following schedule:
The 0 time (pre-dose) blood sample will be collected within 60 minutes prior to first study drug administration.
Cohort l: 0 (pre-dose), 5, 15 and 30 minutes after the first dose and at 1, 2, 4 (prior to second-dose), 4.083, 4.25, 4.5, 5, 6, 8 (prior to third-dose), 8.083, 8.25, 8.5, 9, 10, 12, 16 and 24 hours after the first dose.
Cohort 2: 0 (pre-dose), 5, 15 and 30 minutes after the first dose and at 1, 2 (prior to second-dose), 2.083, 2.25, 2.5, 3, 4 (prior to third-dose), 4.083, 4.25, 4.5, 5, 6, 8, 10, 12, 16 and 24 hours after the first dose.
Cohort 3: 0 (pre-dose), 5, 15, 30 and 45 minutes after the first dose and at 1 (prior to second-dose), 1.083, 1.25, l.5, 1.75, 2 (prior to third-dose), 2.083, 2.25, 2.5, 2.75, 3, 4, 8, 12, 16 and 24 hours after the first dose.
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
- 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
- •Meets protocol-specified criteria for qualification and contraception
- •Willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related food, drink and medications
- •Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures
排除标准
- •History or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
- •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
Cycle 1, Cohort 1
Fentanyl Sublingual Spray (FSS) low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 1, Cohort 1
Fentanyl Sublingual Spray (FSS) low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 1, Cohort 2
FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 1, Cohort 2
FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 1, Cohort 3
FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 1, Cohort 3
FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 1, Cohort 4
FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 1, Cohort 4
FSS low dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 2, Cohort 1
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 2, Cohort 1
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 2, Cohort 2
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 2, Cohort 2
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 2, Cohort 3
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 2, Cohort 3
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 2, Cohort 4
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 2, Cohort 4
FSS medium dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 3, Cohort 1
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 3, Cohort 1
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every four hours for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 3, Cohort 2
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 3, Cohort 2
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every two hours for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 3, Cohort 3
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 3, Cohort 3
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every hour for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
Cycle 3, Cohort 4
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses.
干预措施: Fentanyl Sublingual Spray (Drug)
Cycle 3, Cohort 4
FSS high dose (n=6) or Fentanyl Citrate IV 50 mcg (n=2) will be administered once every 30 minutes for a maximum of three doses.
干预措施: Fentanyl Citrate IV (Drug)
结局指标
主要结局
Dose normalized AUC
时间窗: within 24 hours (see detailed description)
Categories: AUC0-1, AUC0-inf, AUCtau
Time to reach peak or maximum concentration following drug administration (Tmax)
时间窗: within 24 hours (see detailed description)
Apparent elimination rate constant in the terminal phase by non-compartmental analysis
时间窗: within 24 hours (see detailed description)
Trough concentration during multiple dosing prior to next dose (Ctrough)
时间窗: within 24 hours (see detailed description)
Area under the concentration-time curve
时间窗: within 24 hours (see detailed description)
Categories: during a dosing interval (AUCtau ), from the time of dosing to infinity (AUC0-inf), from the time of dosing to the last quantifiable time point (AUC0-t)
Corresponding half-life (t1/2)
时间窗: within 24 hours (see detailed description)
Accumulation ratios
时间窗: within 24 hours (see detailed description)
Categories: of Cmax (ARcmax), based on trough concentration (ARctrough), of AUCtau (ARauctau)
Maximum concentration (Cmax)
时间窗: within 24 hours (see detailed description)
Dose normalized Cmax
时间窗: within 24 hours (see detailed description)
次要结局
- Participants with respiratory depression requiring the use of naloxone(within 24 hours)
- Participants with hypoxia requiring oxygen administration(within 24 hours)
- Participants needing noninvasive respiratory maneuvers (e.g., jaw thrust, bag-valve mask) to improve respiratory status at any point during the study(within 24 hours)
- Participants with hypotension requiring intervention(within 24 hours)