Efficacy, Safety and Pharmacokinetic Profile of a Collagen Bupivacaine Implant in Men After Open Mesh Herniorrhaphy

• Total use of opioid rescue analgesia [ Time Frame: 0 to 48 hours postoperatively ] [ Designated as safety issue: No ]
• Total use of opioid rescue analgesia [ Time Frame: 0 to 72 hours postoperatively ] [ Designated as safety issue: No ]
• Pain intensity on the VAS at rest and after aggravated movement (cough) [ Time Frame: 1, 1.5, 2, 3, 4, 5, 6, 24, 48 and 72 hours after Time 0 ] [ Designated as safety issue: No ]
• Pain intensity rating on a 4-point Likert scale at rest and after aggravated movement (cough) [ Time Frame: At 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 24, 48 and 72 hours after Time 0 ] [ Designated as safety issue: No ]
• Pain relief rating on a 5-point Likert scale at rest and after aggravated movement (cough) [ Time Frame: At 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 24, 48 and 72 hours after Time 0 ] [ Designated as safety issue: No ]
• Patient's global evaluation of the study treatment on a 5 point Likert scale [ Time Frame: At 72 hours after time 0 ] [ Designated as safety issue: No ]
• Time to first use of opioid rescue analgesia [ Time Frame: actual time ] [ Designated as safety issue: No ]
• Pharmacokinetic parameters [ Time Frame: at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 24, 48 and 72 hours after Time 0 ] [ Designated as safety issue: No ]
• Treatment emergent adverse events [ Time Frame: Through 30 days after surgery ] [ Designated as safety issue: Yes ]
• Vital signs (heart rate, respiratory rate, systolic and diastolic blood pressure and body temperature) [ Time Frame: Screening, Baseline and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 24, 48 and 72 hours after Time 0 ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine whether the CollaRx Bupivacaine implant is safe and effective in reducing the amount of narcotic pain medication needed to control pain during the first 24 hours after herniorrhaphy.

Inguinal herniorrhaphy is a common surgery; and common surgical methods used include laparoscopic and open placement of synthetic mesh. The use of synthetic mesh can greatly reduce the risk of hernia recurrence regardless of the method used for its placement. Managing postoperative pain and preventing morbidity after open mesh herniorrhaphy remain considerable medical challenges.

Bupivacaine is a local anesthetic (pain medicine) that has an established safety profile. Collagen is a protein that is found in all mammals. The CollaRx Bupivacaine implant is a thin flat sponge made out of collagen that comes from cow tendons and contains bupivacaine. When inserted into a surgical site, the collagen breaks down and bupivacaine is released at the site but very little is absorbed into the blood stream. The high levels of bupivacaine at the surgical site may result in less pain for several days after surgery.

This study will compare the amount of narcotic pain medication required after surgery in patients who receive either the CollaRx Bupivacaine implant or a plain collagen sponge.

• Postoperative Pain
• Inguinal Hernia

• Drug: Bupivacaine Collagen Sponge
  collagen; Bupivacaine hydrocholoride
  Other Name: CollaRx Bupivacaine Implant
• Drug: placebo collagen sponge
  collagen
  Other Name: Placebo

• Experimental: 1
  Two, 5x5cm bupivacaine collagen sponges implanted during surgery
  Intervention: Drug: Bupivacaine Collagen Sponge
• Placebo Comparator: 2
  Placebo collagen sponge implanted during surgery
  Intervention: Drug: placebo collagen sponge

Inclusion Criteria:

• Has body mass index (BMI) > 19 and < 40 kg/m2.
• Has a planned unilateral inguinal herniorrhaphy (open mesh, tension free technique) to be performed according to standard surgical technique under general anesthesia.
• Has a risk classification of I, II or III according to the ASA.
• Is free of other physical or mental conditions that, in the opinion of the Investigator, may confound the quantification of postoperative pain after herniorrhaphy.
• Has the ability and willingness to comply with the study procedures and the use of the pain scales.
• Is willing to use only permitted medications and anesthetics throughout the study.
• Is willing to use opioid rescue analgesia for moderate to severe incisional pain only.
• Must voluntarily sign and date an informed consent form (ICF) that is approved by an Institutional Review Board (IRB) before the conduct of any study specific procedures.
• Must be able to fluently speak and understand English and be able to provide meaningful written informed consent for the study.

Exclusion Criteria:

• Has a known hypersensitivity to amide local anesthetics, opioids, bovine products or inactive ingredients of the test article.
• Is scheduled for bilateral inguinal herniorrhaphy.
• Has undergone a prior herniorrhaphy on the side that is currently scheduled for repair.
• Has cardiac arrhythmias or atrioventricular (AV) conduction disorders.
• Concomitantly uses antiarrhythmics (eg, amiodarone), propranolol or strong/moderate cytochrome P450 (CYP) 3A4 inhibitors or inducers (eg, macrolide antibiotics and grapefruit juice).
• Has used long acting analgesics within 24 hours of surgery. Short acting analgesics such as acetaminophen may be used on the day of surgery
• Has used aspirin or aspirin containing products within 7 days of surgery. Aspirin at a dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the patient has been on a stable dose regimen for ≥ 30 days before Screening.
• Has undergone major surgery within 3 months of the scheduled herniorrhaphy.
• Has known or suspected history of alcohol or drug abuse or misuse within 3 years of Screening or evidence of tolerance or physical dependency on opioid analgesics or sedative-hypnotic medications.
• Has used opioids or tramadol on an extended daily basis (> 7 days) before surgery. Patients who, in the Investigator's opinion, are developing opioid tolerance are to be excluded.
• Has impaired liver function, aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin ≥ 3.0 times the upper limit of normal (ULN), active hepatic disease, evidence of clinically significant liver disease or another condition (eg, alcoholism, cirrhosis or hepatitis) that may suggest the potential for an increased susceptibility to hepatic toxicity with exposure to test article.
• Has any clinically significant unstable cardiac, neurological, immunological, renal or hematological disease or any other condition that, in the opinion of the Investigator, could compromise the patient's welfare, ability to communicate with the study staff or otherwise contraindicate study participation.
• Is judged by the Investigator to be at risk for infection or slow wound healing.
• Has a chronic painful condition that might confound the assessment of pain associated with the herniorrhaphy.
• Routinely uses pain medication that, in the opinion of the Investigator, could confound the pain assessments during the study.
• Has been treated with agents that could affect the analgesic response (such as central alpha agents, neuroleptic agents and other antipsychotic agents) within 2 weeks of surgery.
• Has been treated with monoamine oxidase inhibitors (MAOIs) within 10 days of surgery.
• Has been treated with systemic corticosteroids within 7 days of surgery (inhaled and topical corticosteroids are allowed).
• Has participated in a clinical trial within 30 days of surgery.