A Phase 2/3, Randomized, Double-blind, Comparator- and Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Efficacy of TLC590 for Postsurgical Pain Management Following Inguinal Hernia Repair
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 415
- 主要终点
- Part 1 - AUC 0-24 of NPRS-M
研究概览
简要总结
A phase 2/3 randomized, double-blind, 2-part, comparator- and placebo-controlled study to assess the safety, pharmacokinetics and efficacy of postsurgical local infiltration in adult subjects following inguinal hernia repair surgery.
详细描述
This is a phase 2/3 randomized, double-blind, 2-part, comparator- and placebo-controlled study to assess the safety, pharmacokinetics and efficacy of postsurgical local infiltration in adult subjects following inguinal hernia repair surgery. This study includes 2 parts. An unblinded interim analysis will be performed after completion of part 1 (phase 2, approximately 115 subjects to be randomized for 2 different doses of TLC590, bupivacaine, ropivacaine, or placebo), for selecting a TLC590 dose for part 2 (phase 3, approximately 300 subjects to be randomized for TLC590, bupivacaine, or placebo).In this study, 2 doses of TLC590 24.5 mg/mL in inguinal hernia repair will be assessed in an initial phase 2 part before proceeding to a phase 3 pivotal evaluation.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Male or female at least 18 years old
- •BMI 18-39 kg/m2
- •Scheduled to undergo a primary, unilateral Lichtenstein inguinal hernia repair with mesh
- •ASA Physical Status Classification of 1, 2 or 3
排除标准
- •Clinically significant abnormal clinical laboratory test value
- •Clinically significant 12-lead ECG
- •History of orthostatic hypotension or syncope
- •History of significant renal, hepatic, gastrointestinal, cardiovascular, metabolic, neurologic, psychiatric, or other condition
- •History of seizure or currently taking anticonvulsants
- •History of hypersensitivity to bupivacaine/ropivacaine, any other amide-type local anesthetic, propofol, oxycodone or morphine (or other opioids)
- •History of severe or refractory post-operative nausea or vomiting (PONV)
- •Abnormalities of laboratory parameters: HbA1c, platelet, hemoglobin, WBC, serun bilirubin/alanine aminotransferase/aspartate aminotrasferase, serum creatinine, PTT/INR
- •Concurrent acute, or chronic painful restrictive/physical condition
- •Received opioid therapy for longer than 4 days per week
- •Prohibited medication: aspirin and other anti-platelet medication, anticoagulants, class III antiarrhythmic drugs, strong CYP1A2 inhibitors,systemic corticosteroids, NSAID, opioid, bupivacaine or ropivacaine, any investigational product
- •History of drug abuse or alcohol abuse
- •Positive results on the urine drug screen or alcohol breath test
- •History of HIV; active HBV or HCV
- •An inguinal hernia repair in the last 3 months or has undergone 3 or more surgeries within 12 months
- •Malignancy in the last 2 years
- •Documented sleep apnea or on home continuous positive airway pressure treatment (CPAP)
- •Personal or family history of malignant hyperthermia.
研究组 & 干预措施
TLC590 490mg
TLC590 490mg (20mL)
干预措施: TLC590 (Drug)
TLC590 588mg
TLC590 588mg (24mL)
干预措施: TLC590 (Drug)
Bupivacaine 75mg
Bupivacaine HCl 75mg (30mL)
干预措施: Bupivacain (Drug)
Ropivacaine
Ropivacaine HCl 150mg (30mL) (Part 1)
干预措施: Ropivacaine (Drug)
Normal saline
Normal Saline 0.9% (20mL or 24mL)
干预措施: Normal saline (Drug)
结局指标
主要结局
Part 1 - AUC 0-24 of NPRS-M
时间窗: 0-24 hours
AUC 0-24 of NPRS-M, evaluated comparing each dose of TLC590 with Placebo
Part 2 - AUC 0-72 of NPRS-M
时间窗: 0-72 hours
AUC 0-72 of NPRS-M, evaluated comparing each dose of TLC590 with Placebo
次要结局
- AUC 0-72 of NPRS-M (active comparator)(0-72 hours)
- Proportion of opioid-free subjects through 72 hours (active comparator)(0-72 hours)
- Proportion of opioid-free subjects through 72 hours (placebo)(0-72 hours)