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

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

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.

Study Overview

• Status: Completed
• Conditions: Inguinal Hernia
• Intervention / Treatment: Drug: SKY0402; Drug: Bupivacaine HCl

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 Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bupivacaine HCl; (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; Single dose of SKY0402 administered locally into the surgical wound.
Active Comparator: SKY0402; Low dose, low-mid dose, mid-dose, and high dose	Drug: Bupivacaine HCl; Single dose of bupivacaine HCl (100 mg) administered locally into the surgical wound.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Investigators: Study Director: Kay Warnott, RN, ACNP, Pacira Pharmaceuticals, Inc

Publications and helpful links

General Publications

• Dasta J, Ramamoorthy S, Patou G, Sinatra R. Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. Curr Med Res Opin. 2012 Oct;28(10):1609-15. doi: 10.1185/03007995.2012.721760. Epub 2012 Sep 3.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 16, 2010

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Analgesia; Postoperative pain
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hernia, Abdominal; Hernia; Hernia, Inguinal; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: SKY0402-C-201