Phase 2/3 Study of TLC590 for Postsurgical Pain Management

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

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 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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.