A Phase 1, Pilot, Open Label, Dose Escalation Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety, of EXPAREL Administered as Sciatic Nerve Block (In Popliteal Fossa), for Postsurgical Analgesia in Subjects Undergoing Bunionectomy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Pharmacodynamic 1 (duration of sensory and motor block)
研究概览
简要总结
This is a pilot, open label, single center study in 40 subjects undergoing bunionectomy. The study will assess and collect information on pharmacokinetics, pharmacodynamics, safety and efficacy of EXPAREL administered as a sciatic nerve block (in popliteal fossa).
A total of 10 subjects will be enrolled in each of the 4 cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Healthy adult male or female volunteers ages 18 or older
- •American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
- •Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
- •Body Mass Index ≥18 and ≤40 kg/m2
排除标准
- •Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (eg, amide-type local anesthetics, opioids, bupivacaine, NSAIDs)
- •Documented history of long-term diabetes or severe peripheral vascular disease
- •Renal (serum creatinine level >2mg/dL [176.8 μmol/L]) or hepatic dysfunction (serum alanine or aspartame transferase > 3 times the upper limit of normal).
- •Concurrent painful physical condition that may require analgesic treatment (such as long-term, consistent use of opioids) in the post dosing period for pain and which, in the investigator's opinion may confound the post dosing assessments
- •History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years
- •Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study
- •Previous participation in an EXPAREL study
- •Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance
- •Currently pregnant, nursing, or planning to become pregnant during the study
- •Clinically significant medical disease that, in the opinion of the investigator, would make participation in a clinical study inappropriate. This includes any psychiatric or other conditions that would constitute a contraindication to participation in the study
- •Currently on neuroleptic agent [e.g., gabapentin, pregabalin (Lyrica), duloxetine (Cymbalta) etc.]
- •Inadequate sensory function on the foot (monofilament test)
- •Chronic opioid use in the last 30 days (≥30 morphine equivalents/ day)
- •In addition, the subject may be withdrawn from the study if the subject meets the following criterion during or post-surgery:
- •Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that, in the opinion of the investigator, renders the subject medically unstable or complicates the subject's post-operative course
研究组 & 干预措施
Cohort 1 - EXPAREL
A total of 10 subjects will be enrolled. Subjects in this cohort will receive 266mg of EXPAREL admixed with bupivacaine.
干预措施: Exparel Injectable Product (Drug)
Cohort 1 - EXPAREL
A total of 10 subjects will be enrolled. Subjects in this cohort will receive 266mg of EXPAREL admixed with bupivacaine.
干预措施: Bupivacaine (Drug)
Cohort 2 - EXPAREL
A total of 10 subjects will be enrolled. Subjects in this cohort will receive 133mg of EXPAREL admixed with bupivacaine.
干预措施: Exparel Injectable Product (Drug)
Cohort 2 - EXPAREL
A total of 10 subjects will be enrolled. Subjects in this cohort will receive 133mg of EXPAREL admixed with bupivacaine.
干预措施: Bupivacaine (Drug)
Cohort 3 - EXPAREL
A total of 10 subjects will be enrolled. Subjects in this cohort will receive 266mg of EXPAREL only
干预措施: Exparel Injectable Product (Drug)
Cohort 4 - bupivacaine
A total of 10 subjects will be enrolled. Subjects in this cohort will receive 100mg Bupivacaine only.
干预措施: Bupivacaine (Drug)
结局指标
主要结局
Pharmacodynamic 1 (duration of sensory and motor block)
时间窗: up to 15 min before block, 15 min(±5 min), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1), 60(±2), 72(±2), 84(±2), 96(±3), 120(±3), 144(±3), and 168(±3) hours following block
Average duration of sensory block and motor block
Pharmacokinetic 1 (Area under the plasma concentration)
时间窗: predose (up to 15 min before block), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1), 60(±2), 72(±2), 84(±2), 96(±3), 120(±3), 144(±3), and 168(±3) hours following block
Area under the plasma concentration-versus-time curve (AUC).
Pharmacokinetic 3 (half-life )
时间窗: predose (up to 15 min before block), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1h), 60(±2h), 72(±2h), 84(±2h), 96(±3h), 120(±3h), 144(±3h), and 168(±3h) hours following block
The apparent terminal elimination half-life (t1/2el).
Pharmacokinetic 2 (Cmax)
时间窗: predose (up to 15 min before block), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1h), 60(±2h), 72(±2h), 84(±2h), 96(±3h), 120(±3h), 144(±3h), and 168(±3h) hours following block
Maximum plasma concentration (Cmax)
Pharmacokinetic 4 (Apparent clearance)
时间窗: predose (up to 15 min before block), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1h), 60(±2h), 72(±2h), 84(±2h), 96(±3h), 120(±3h), 144(±3h), and 168(±3h) hours following block
Apparent clearance (CL/F).
Pharmacokinetic 5 (volume of distribution)
时间窗: predose (up to 15 min before block), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1h), 60(±2h), 72(±2h), 84(±2h), 96(±3h), 120(±3h), 144(±3h), and 168(±3h) hours following block
Apparent volume of distribution (Vd).
Pharmacokinetic 6 (Tmax)
时间窗: predose (up to 15 min before block), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1h), 60(±2h), 72(±2h), 84(±2h), 96(±3h), 120(±3h), 144(±3h), and 168(±3h) hours following block
Time of Cmax (Tmax)
Pharmacodynamic 2 (duration of sensory and motor block)
时间窗: up to 15 min before block, 15 min(±5min), 30 min(±5min), 45 min(±5min), and 60 min (±15min) and 30 min(±5min), 45 min(±5min), 1(±15min), 2(±30min), 12(±30min), 24(±1), 60(±2), 72(±2), 84(±2), 96(±3), 120(±3), 144(±3), and 168(±3) hours following block
Average duration of sensory block and motor block
次要结局
未报告次要终点