Phase 2/3 Study of TLC590 for Postsurgical Pain Management

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Postsurgical Pain Management

Intervention / Treatment
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* Drug: TLC590
* Drug: Bupivacain
* Drug: Ropivacaine
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TLC590 490mg<br>TLC590 490mg (20mL) | Drug: TLC590<br>* TLC590 490mg or 588mg<br>* Other names: intestigational drug;|
| Experimental: TLC590 588mg<br>TLC590 588mg (24mL) | Drug: TLC590<br>* TLC590 490mg or 588mg<br>* Other names: intestigational drug;|
| Active Comparator: Bupivacaine 75mg<br>Bupivacaine HCl 75mg (30mL) | Drug: Bupivacain<br>* Bupivacaine 75mg<br>* Other names: active comparator;|
| Active Comparator: Ropivacaine<br>Ropivacaine HCl 150mg (30mL) (Part 1) | Drug: Ropivacaine<br>* Ropivacaine 150mg<br>* Other names: active comparator;|
| Placebo Comparator: Normal saline<br>Normal Saline 0.9% (20mL or 24mL) | Drug: Normal saline<br>* Normal saline 20mL or 24mL<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 - AUC 0-24 of NPRS-M | AUC 0-24 of NPRS-M, evaluated comparing each dose of TLC590 with Placebo | 0-24 hours | 
| Part 2 - AUC 0-72 of NPRS-M | AUC 0-72 of NPRS-M, evaluated comparing each dose of TLC590 with Placebo | 0-72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-72 of NPRS-M (active comparator) | AUC 0-72 of NPRS-M (TLC590 vs Bupivacaine) | 0-72 hours | 
| Proportion of opioid-free subjects through 72 hours (placebo) | Proportion of opioid-free subjects through 72 hours (TLC590 vs. Placebo) | 0-72 hours | 
| Proportion of opioid-free subjects through 72 hours (active comparator) | Proportion of opioid-free subjects through 72 hours (TLC590 vs. Bupivacaine) | 0-72 hours |