A Phase 3, Randomized, Double-Blind, Active-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL vs. Bupivacaine Hydrochloric Acid (HCl) Administered as a Sciatic (in the Popliteal Fossa) Nerve Block for Postsurgical Analgesia in Subjects Undergoing Bunionectomy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 185
- 试验地点
- 7
- 主要终点
- NRS Pain Scores Through 96 Hours Post-surgery
研究概览
简要总结
The study is conducted sequentially in two parts.
Part A: The purpose is to obtain information on pharmacokinetic (PK) profile, pharmacodynamics (PD), efficacy, safety, and to assess the performance of 266 mg EXPAREL vs 133 mg EXPAREL.
Part B: The purpose is to evaluate the efficacy and safety of the preferred dosage of EXPAREL from Part A compared with bupivacaine HCl.
详细描述
This is a Phase 3, multicenter, randomized, double-blind, active controlled study in approximately 180 subjects undergoing bunionectomy. The study will be conducted in two parts (Part A and Part B). Part A will be completed and analyzed before enrollment in Part B is initiated.
Subjects may be screened up to 45 days prior to the day of surgery but eligibility must be re-confirmed on the day of surgery prior to randomization.
The following screening procedures will be performed after the informed consent form (ICF) is signed (if not standard of care): assess eligibility, record medical/surgical history, record prior and concomitant medications, record demographics and baseline characteristics, record subject height and weight for body mass index (BMI) calculation, assess chronic opioid use in the past 30 days, conduct urine pregnancy test for women of childbearing potential, perform 12-lead EKG, record serious adverse events (SAEs) starting when the ICF is signed, and record medications for treatment of SAEs.
On Day 1, prior to sciatic nerve block, study staff will review Pain Rating Guide with the subject and record their responses to:
- Numeric rating scale (NRS) score on the worst pain of their operative foot in the last 30 days.
- NRS score on the average pain of their operative foot in the last 30 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Individuals preparing and administering study drug, or transporting unblinded drug will not be allowed to perform any of the study assessments after randomization (with the possible logistical exception of drawing blood in the operating room (OR) to be processed by blinded staff for the PK assessments) or reveal the assigned study treatment to any other members of the study team at any time. Additionally, efforts will be made to prevent the subject from observing the study drug syringe. Staff members conducting study-specific, postsurgical assessments and the subjects will remain blinded to the assigned treatment throughout the study in part by not being present during the administration of the nerve block. The site PI must be blinded to the study drug and will not be involved in and/or present during study drug administration. No crossover will be permitted between the blinded and unblinded study personnel throughout the study.
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
- •Male or female, ages 18 or older at screening
- •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
- •Primary surgical indication is related to a bunion deformity (i.e., hallux valgus) and subject is scheduled to undergo a distal metaphyseal osteotomy procedure (e.g., Austin procedure as opposed to Lapiplasty, Lapidus bunionectomies or base wedge bunionectomies)
- •Indicated to undergo elective (i.e., not emergency) bunionectomy
- •Body Mass Index (BMI) ≥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 (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs)
- •Concurrent painful physical condition (e.g. arthritis, fibromyalgia, cancer) that may require analgesic treatment with NSAIDs or opioids in the post dosing period for pain that is not strictly related to the foot surgery and which, in the Investigator's opinion, may confound the post dosing assessments
- •Inadequate sensory function of the foot/ankle as assessed by the Investigator
- •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 diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction or other conditions that would constitute a contraindication to participation in the study
- •Currently on a neuromodulating agent (e.g., gabapentin, pregabalin [Lyrica], duloxetine [Cymbalta], etc.)
- •Current use of systemic glucocorticoids within 30 days of randomization in this study
- •Use of dexmedetomidine HCl (Precedex®) or clonidine within 3 days of study drug administration
- •Any use of marijuana (including tetrahydrocannabinol (THC) and cannabidiol (CBD)) within 30 days prior to randomization, or planned use during the course of the study
- •Chronic opioid use within 30 days prior to randomization (average ≥30 oral morphine equivalents/day)
研究组 & 干预措施
Part A: EXPAREL 266 mg arm
subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 10 mL saline
干预措施: Bupivacaine liposome injectable suspension 266 mg (Drug)
Part A: EXPAREL 133 mg arm
subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL mixed with 20 mL saline
干预措施: Bupivacaine liposome injectable suspension 133 mg (Drug)
Part A: Bupivacaine HCl arm
Subjects randomized to this treatment arm will receive 20 mL (50 mg) 0.25% bupivacaine HCl mixed with 10 mL saline
干预措施: Bupivacaine HCl (Drug)
Part B: EXPAREL 133 mg arm OR EXPAREL 266 mg arm
Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 10 mL saline OR 10 mL (133 mg) EXPAREL mixed with 20 mL saline. Dose will be determined following interim analysis of Part A.
干预措施: Bupivacaine liposome injectable suspension 133 mg (Drug)
Part B: Bupivacaine HCl arm
subjects randomized to this treatment arm will receive 20 mL (50 mg) 0.25% bupivacaine HCl mixed with 10 mL saline
干预措施: Bupivacaine HCl (Drug)
结局指标
主要结局
NRS Pain Scores Through 96 Hours Post-surgery
时间窗: 0- 96 hours post-surgery
The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.
次要结局
- First Opioid Consumption Post-surgery(0 to 96 hours post-surgery)
- Postsurgical Opioid Consumption Through 96 Hours Post-surgery(0 to 96 hours post-surgery)
- Opioid-free Subjects Through 96 Hours Post-surgery(0 to 96 hours post-surgery)
- NRS Pain Scores Post-surgery(0-24 hours, 24-48 hours, 48-72 hours, and 72-96 hours post-surgery)