A Phase 2b, Randomized, Double-Blind, Saline Placebo- and Active-Controlled, Multicenter Study of HTX-011 Via Infiltration for Postoperative Analgesia in Subjects Undergoing Total Knee Arthroplasty
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 285
- 试验地点
- 24
- 主要终点
- Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48).
研究概览
简要总结
This is a Phase 2b, randomized, double-blind, saline placebo- and active-controlled, multicenter study in subjects undergoing primary unilateral total knee arthroplasty (TKA) to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 administered via infiltration to the surgical site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
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
- •Is scheduled to undergo primary unilateral TKA under general anesthesia.
- •Has not previously undergone TKA in either knee.
- •Has an American Society of Anesthesiologists Physical Status of I, II, or III.
- •Is able to demonstrate motor function by performing a timed 20-meter walk unassisted, but with the optional use of a 4-legged walker for balance.
- •Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives.
排除标准
- •Has a planned concurrent surgical procedure (eg, bilateral TKA).
- •Has a pre-existing concurrent acute or chronic painful/restrictive physical condition that may require analgesic treatment in the postoperative period for pain.
- •Has a contraindication or a known or suspected history of hypersensitivity or idiosyncratic reaction to required study medications.
- •Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
- •Has taken NSAIDs within 10 days prior to the scheduled surgery.
- •Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting).
- •Has been administered bupivacaine within 5 days prior to the scheduled surgery.
- •Has initiated treatment with medications within 1 month prior to study drug administration that can impact pain control.
- •Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug.
- •Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments.
- •Has a known history of Hepatitis B, human immunodeficiency virus (HIV), or active Hepatitis C.
- •Has uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
- •Has any chronic neuromuscular deficit of either femoral nerve function or thigh musculature. Has any chronic condition or disease that would compromise neurological or vascular assessments.
- •Had a malignancy in the last year, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
- •Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse.
- •Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
- •Has undergone 3 or more surgeries within 12 months.
- •Has a body mass index (BMI) >38 kg/m2.
研究组 & 干预措施
Cohort 1, Group 1: HTX-011
HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via instillation
干预措施: HTX-011 (Drug)
Cohort 1, Group 2: HTX-011
HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via injection and instillation (combination)
干预措施: HTX-011 (Drug)
Cohort 1, Group 3: Saline Placebo
Saline placebo via injection
干预措施: Saline Placebo (Drug)
Cohort 1, Group 4: Bupivacaine HCI
Bupivacaine HCl without epinephrine, 125 mg via injection
干预措施: Bupivicaine HCl (Drug)
Cohort 2, Group 1: HTX-011
HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation
干预措施: HTX-011 (Drug)
Cohort 2, Group 2: HTX-011 + Ropivacaine
HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation; Ropivacaine, 50 mg via injection
干预措施: HTX-011 (Drug)
Cohort 2, Group 2: HTX-011 + Ropivacaine
HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation; Ropivacaine, 50 mg via injection
干预措施: Ropivacaine (Drug)
Cohort 2, Group 3: Saline Placebo
Saline placebo via injection
干预措施: Saline Placebo (Drug)
Cohort 2, Group 4: Bupivacaine HCI
Bupivacaine HCl without epinephrine, 125 mg via injection
干预措施: Bupivicaine HCl (Drug)
结局指标
主要结局
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48).
时间窗: 48 hours
Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-48 is 0-480.
次要结局
- Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 72 Hours Postsurgery (AUC0-72).(72 hours)
- Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)(72 hours)