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

Phase 2

Completed

• Conditions: Inguinal Hernia
• Interventions: Drug: SKY0402; Drug: Bupivacaine HCl

• Registration Number: NCT01203644
• Lead Sponsor: Pacira Pharmaceuticals, Inc

Brief Summary

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

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.

Study Timeline

• Study Start: 2004-12
• Primary Completion: 2006-01
• Study Completion: 2006-12
• Study First Submitted: 2010-09-15
• Study First Submitted QC: 2010-09-15
• Study First Posted: 2010-09-16
• Disposition First Submitted: 2010-09-22
• Disposition First Submitted QC: 2010-09-22
• Disposition First Posted: 2010-09-27
• Results First Submitted: 2011-11-23
• Results First Submitted QC: 2012-04-15
• Results First Posted: 2012-05-14
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-04
• Last Update Posted: 2021-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 76

Inclusion Criteria

1. Males ≥18 years of age at the Screening visit.
2. Scheduled to undergo unilateral inguinal hernia repair under general anesthesia, using an open, tension free procedure (e.g., Lichtenstein technique with or without mesh).
3. American Society of Anesthesiology (ASA) Physical Class 1 or 2.
4. Able and willing to comply with all study visits and procedures.
5. Capable of speaking and understanding the local language sufficiently to provide responses to pain assessment scales.
6. Willing and capable of providing written informed consent.

Exclusion Criteria

1. Clinically significant electrocardiogram abnormalities at Screening or on Day 1 (pre administration).
2. Albumin and/or alpha 1 acid glycoprotein (AAG) below normal levels.
3. 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.
4. Opioid medication usage during the 7 day period preceding the administration of study drug.
5. 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).
6. Body mass index >30 kg/m^2
7. Body weight <60 kg.
8. History of hypersensitivity or idiosyncratic reaction to amide type local anesthetic agents.
9. 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.
10. Coagulation disorders or ongoing anticoagulation treatment.
11. Administration of an investigational drug within 30 days or five half lives (of elimination), whichever was longer, prior to study drug administration.
12. Suspected or known history of substance abuse and/or alcoholism.
13. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bupivacaine HCl	SKY0402	(e.g., Marcaine with epinephrine 1:200,000) is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402
SKY0402	Bupivacaine HCl	Low dose, low-mid dose, mid-dose, and high dose

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adverse Events	Through 30 days postdose	Safety assessments included monitoring of treatment-emergent adverse events