Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty

This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled
study in adults who are scheduled for unilateral inguinal hernioplasty via open laparotomy
(tension-free technique). Patients will receive either 3 XaraColl Bupivacaine Implants each
containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose; or 3
placebo-sponges.

Three test article sponges will be implanted according to the patient's blinded treatment
assignment. Following surgery, patients will be transferred to a postanesthesia care unit
(PACU) and/or other postoperative recovery area for observation where they may receive
parenteral morphine as needed (rescue medication for breakthrough pain) and on request for
pain control. Once patients can tolerate oral medication, they will commence a standardized
oral analgesic regimen with additional PRN medication to manage breakthrough pain only when
it occurs.

Patients will assess their postoperative pain intensity (PI) using an 11-point numerical
rating scale (NRS) from 0 hour through 72 hours postoperatively.

Patients will be observed postoperatively for a minimum of 3 hours and may be discharged at
any time following completion of their 3-hour vital sign and PI assessments. Patients will
be contacted at approximately 6, 24 and 48 hours after implantation to ensure protocol
compliance and to perform safety assessments (including AEs and concomitant medications). At
72 hours, patients will return to the clinic to perform their final PI assessment, complete
a categorical assessment of their overall pain control, and for follow-up safety
assessments. They will also be asked to record the incidence of any ongoing or subsequent
AEs (and any associated treatment) through Day 7. Additional follow-up assessments for
safety will be performed at postoperative Day 7 (telephone call) and Days 15 and 30 (clinic
visits).

Inclusion Criteria:

- Has a planned (non-emergent) unilateral inguinal hernioplasty (open laparotomy,
tension-free technique) to be performed according to standard surgical technique
under general anesthesia. Repair of multiple hernias through a single incision is
permitted provided only a single mesh will be used.

- If female, is nonpregnant and nonlactating.

- If female, is either not of childbearing potential (defined as postmenopausal for ≥ 1
year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or
hysterectomy]) or practicing 1 of the protocol specified medically-acceptable methods
of birth control and agrees to continue with the regimen throughout the duration of
the study:

- Has the ability and willingness to comply with the study procedures and use of the
eDiary.

- Is willing to use only permitted medications throughout the study.

- Is willing to use opioid analgesia.

- Must be able to fluently speak and understand either English or Spanish and be able
to provide meaningful written informed consent for the study.

Exclusion Criteria:

- Has a known hypersensitivity to amide local anesthetics, morphine, acetaminophen or
bovine products.

- Is scheduled for bilateral inguinal hernioplasty or other significant concurrent
surgical procedures per investigator discretion.

- Has undergone major surgery within 3 months of the scheduled hernioplasty or plans to
undergo another laparotomy procedure within 30 days postoperatively.

- Has used any analgesic other than acetaminophen within 24 hours of surgery.
Acetaminophen may be used on the day of surgery but is subject to preoperative
restrictions for oral intake.

- 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 used systemic steroids, anticonvulsants, antiepileptics, antidepressants for the
management of chronic pain, or monoamine oxidase inhibitors on a regular basis within
10 days of surgery.

- Has used any opioid analgesic for an extended daily basis (30 - 60 mg oral morphine
equivalent per day for 3 or more days a week) within 4 weeks before surgery. Patients
who, in the investigator's opinion, may be developing opioid tolerance are also
excluded.

- Has any chronic painful condition (eg, fibromyalgia) or routinely uses pain
medication other than acetaminophen (including nonsteroidal anti-inflammatory drugs
[NSAIDs]) that, in the opinion of the investigator, may confound the assessment of
pain associated with the hernioplasty.

- Has a physical or mental condition that, in the opinion of the investigator, may
confound the assessment of postoperative pain after hernioplasty.

- Shows evidence of tolerance or physical dependency on opioid analgesics or
sedative-hypnotic medications.

- Has a urine drug screen that tests positive for drugs of abuse or misuse, including
cannabinoids.

- Has liver function test results greater than 3x the upper limit of normal or a
history of cirrhosis.

- Has any clinically significant unstable cardiac disease (eg, uncontrolled
hypertension, clinically significant arrhythmia at baseline, or an implantable
cardioverter-defibrillator [ICD])

- Has any clinically significant unstable neurological, immunological, renal, or
hematological disease (eg, uncontrolled diabetes or significantly abnormal laboratory
findings), 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.

- Has an open workman's compensation claim.

- Has participated in a clinical trial (investigational or marketed product) within 30
days of surgery.