Evaluation of the Safety, Efficacy, and Pharmacokinetics of SKY0402 in Subjects Undergoing Inguinal Hernia Repair

Study Overview
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Brief Summary
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The primary objective of this study was to determine the appropriate dose of SKY0402 for the management of postoperative pain following inguinal hernia repair. This study evaluated the safety, efficacy, and pharmacokinetics of SKY0402 compared with a 100 mg dose of bupivacaine HCl for the treatment of postoperative pain in subjects undergoing inguinal hernia repair. Study drug was administered by surgical wound infiltration at the end of the hernia repair procedure.

Detailed Description
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SKY0402 was administered in a dose escalating/de-escalating fashion, with a low starting dose in Cohort 1 that was to be increased or decreased in subsequent cohorts based on safety and analgesic effects. The decision to proceed to the next cohort (i.e., increase or decrease the dose) was made by a Cohort Data Review Committee following a review of the data from the previous cohort. Subjects were randomized to receive either SKY0402 or bupivacaine HCl at a ratio of 1:1 in Cohort 1 and at a ratio of 3:1 in subsequent cohorts. The dose of bupivacaine HCl (100 mg) remained constant for all cohorts.

Official Title
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A Phase 2, Multicenter, Randomized, Double Blind, Dose Escalating/ De Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of a Single Dose of Sustained Release Encapsulated Bupivacaine (SKY0402) in the Management of Postoperative Pain in Subjects Undergoing Inguinal Hernia Repair

Conditions
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Inguinal Hernia

Intervention / Treatment
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* Drug: SKY0402
* Drug: Bupivacaine HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males ≥18 years of age at the Screening visit. Scheduled to undergo unilateral inguinal hernia repair under general anesthesia, using an open, tension free procedure (e.g., Lichtenstein technique with or without mesh). American Society of Anesthesiology (ASA) Physical Class 1 or 2. Able and willing to comply with all study visits and procedures. Capable of speaking and understanding the local language sufficiently to provide responses to pain assessment scales. Willing and capable of providing written informed consent. Exclusion Criteria: Clinically significant electrocardiogram abnormalities at Screening or on Day 1 (pre administration). Albumin and/or alpha 1 acid glycoprotein (AAG) below normal levels. Current or historical evidence of any clinically significant disease or condition that, in the opinion of the Investigator, might have increased the risk of surgery or complicated the subject's postoperative course. Opioid medication usage during the 7 day period preceding the administration of study drug. Current medical conditions that could have required treatment with analgesic medications in the postoperative period for pain that was not surgically related (e.g., rheumatoid arthritis). Body mass index >30 kg/m^2 Body weight <60 kg. History of hypersensitivity or idiosyncratic reaction to amide type local anesthetic agents. History of hypersensitivity, idiosyncratic reactions, and other contraindications to the pain control agents (opioid or non-opioid) anticipated to be used postoperatively. These contraindications may have included: angioedema and bronchospastic reactivity to non steroidal anti inflammatory drug, peptic ulcer (active within the last three months), hepatic or renal insufficiency. Coagulation disorders or ongoing anticoagulation treatment. Administration of an investigational drug within 30 days or five half lives (of elimination), whichever was longer, prior to study drug administration. Suspected or known history of substance abuse and/or alcoholism. Clinically significant complications during the hernia repair surgery (e.g., excessive bleeding), which might have rendered the subject medically unstable or might have complicated the subject's postoperative course.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bupivacaine HCl<br>(e.g., Marcaine with epinephrine 1:200,000) is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402 | Drug: SKY0402<br>* Single dose of SKY0402 administered locally into the surgical wound.<br>|
| Active Comparator: SKY0402<br>Low dose, low-mid dose, mid-dose, and high dose | Drug: Bupivacaine HCl<br>* Single dose of bupivacaine HCl (100 mg) administered locally into the surgical wound.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Use of Supplemental Pain Medication | The primary efficacy endpoint was the time to first use of supplemental pain medication (opioid or non-opioid) postoperatively for surgical wound pain | Through 96 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Safety assessments included monitoring of treatment-emergent adverse events | Through 30 days postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative pain, Analgesia