An Open-Label Single-Dose Crossover Study Comparing the Plasma and Cerebrospinal Fluid Pharmacokinetics and Bioavailability of Fentanyl Delivered Intranasally Versus Sublingually Versus Intravenously in Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 主要终点
- Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) of Fentanyl in Plasma (3 of 5)
研究概览
简要总结
A partially randomized, open-label, 3-way crossover, single-center, systemic and CSF PK and bioavailability study in healthy volunteers.
详细描述
An Open-Label Single-Dose Crossover Study Comparing the Plasma and Cerebrospinal Fluid Pharmacokinetics and Bioavailability of Fentanyl Delivered Intranasally Versus Sublingually Versus Intravenously in Healthy Volunteers
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal healthy male or female between the ages of 18 to 65 years. Never smokers or Non-smokers (cessation of smoking ≥ 6 months ago). Body Mass Index (BMI = weight/height2) greater than or equal to 18.5 kg/m2 and less than or equal to 32.0 kg/m
- •No clinically meaningful findings in the physical examination, oral and nasal examination and 12-lead electrocardiogram.
- •Negative for drugs of abuse, alcohol, and nicotine. Negative for hepatitis A, B, and C and Human Immunodeficiency Virus (HIV). No clinical laboratory values outside of the acceptable range, unless, in the opinion of the Principal Investigator, they are deemed not clinically significant.
排除标准
- •Subject has a known history of allergic reaction, hypersensitivity, or clinically significant intolerance to opioids, fentanyl or components of the study drugs.
- •Subjects with a high potential for opioid addiction (personal or family history).
- •Subject is lactating or considered at risk of pregnancy.
- •Subject has impaired liver function (e.g., alanine aminotransferase [ALT] ≥ 3 times the upper limit of normal [ULN] or bilirubin ≥ 3 times ULN), known active hepatic disease (e.g., hepatitis), or evidence of clinically significant liver disease or other condition affecting the liver that may suggest the potential for an increased susceptibility to hepatic toxicity with oral diclofenac exposure.
- •Subject has any history of renal disease that, in the opinion of the investigator, would contraindicate study participation; or subject has significantly impaired renal function as evidenced by an estimated GFR of ≤60 ml/min/1.73m
- •Subject has a history or evidence of significant nasal pathology, including polyps or nasal obstructions.
研究组 & 干预措施
Nasal fentanyl
nasal fentanyl, 200 μg, administered as one 100 μg spray (100 μL) to each nostril; both completed within one minute.
Will be administered on either study day 1 or 3 per protocol and randomization.
干预措施: Fentanyl (Drug)
Sub-Lingual fentanyl
sublingual fentanyl, 200 μg, administered as a single spray (100 μL) under the tongue.
Will be administered on either study day 1 or 3 per protocol and randomization.
干预措施: Fentanyl (Drug)
IV fentanyl
IV fentanyl, 100 μg in 2 mL administered as an intravenous injection over 1-3 minutes.
Will be administered on study day 5 per protocol.
干预措施: Fentanyl (Drug)
结局指标
主要结局
Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) of Fentanyl in Plasma (3 of 5)
时间窗: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)
AUC 0-inf (pg\*h/mL)
Time to Reach Maximum Observed Concentration (Tmax) of Fentanyl in Plasma (4 of 5)
时间窗: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)
Tmax (h)
Terminal Elimination Half-Life (t1/2) of Fentanyl in Plasma (5 of 5)
时间窗: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)
t1/2 (h)
Time to Reach Maximum Observed Concentration (Tmax) of Fentanyl in Cerebrospinal Fluid (CSF) (1 of 3)
时间窗: 6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)
Maximum Observed Concentration (Cmax) of Fentanyl in Cerebrospinal Fluid (CSF) (2 of 3)
时间窗: 6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)
Maximum Observed Concentration (Cmax) of Fentanyl in Plasma (1 of 5)
时间窗: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)
Cmax (pg/mL)
Area Under the Concentration-Time Curve From Hour 0 to Hour 6 (AUC 0-6h) of Fentanyl in Cerebrospinal Fluid (CSF) (3 of 3)
时间窗: 6 hrs (pre-dose, 5, 10, 20, 30, 45, & 60 min, and 2, 3, 4, & 6 hrs post-dose on Study Days 1 & 3)
Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUC 0-tlast) of Fentanyl in Plasma (2 of 5)
时间窗: 24 hrs (pre-dose, 5, 10, 15, 20, 30, 45, & 60 min, and 1.5, 2, 3, 4, 6, 8, 12, & 24 hrs on Study Days 1 & 3 for Nasal Fentanyl / Sublingual Fentanyl; pre-dose, 2, 5, 10, 20, 30, & 60 min, and 2, 4, 6, 8, 12, & 24 hrs on Study Day 5 for IV Fentanyl)
AUC 0-tlast (pg\*h/mL)
次要结局
未报告次要终点