Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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
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.


Options:
A: Inclusion Criteria:

* Age \> 18 years of age at the Screening visit
* American Society of Anesthesiologists (ASA) class 1-3
* Scheduled to have a two or three column excisional hemorrhoidectomy under general anesthesia using the Milligan-Morgan technique
* For female subjects, surgically sterile or at least two years menopausal, or using an acceptable method of birth control; must have a documented negative blood or urine pregnancy test within 24 hours before surgery
* Clinical lab values less than or equal to twice the upper limit of normal or, if abnormal, deemed not clinically significant per the Investigator.
* Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
* Able to speak, read, and understand the language of all subject-facing documents, including the ICF and study questionnaires
* Able and willing to comply with all study visits and procedures

Exclusion Criteria:

* Single-column hemorrhoidectomy or hemorrhoidectomy without an internal component
* Body weight less than 50 kilograms (110 pounds)
* History of hypersensitivity or idiosyncratic reactions or amide-type local anesthetics, opioids, or propofol
* Current painful physical condition or concurrent surgery other than hemorrhoids that may require analgesic treatment (such as non-steroidal anti-inflammatory drug \[NSAID\], opioid, selective serotonin reuptake inhibitor \[SSRI\], tricyclic antidepressant, gabapentin, pregabalin) in the postoperative period for pain that is not strictly related to the hemorrhoidectomy procedure and may confound the postoperative assessments
* Concurrent fissurectomy
* Use of any NSAID including selective COX-2 inhibitor, opioid, SSRI, tricyclic antidepressant, gabapentin, or pregabalin within three days of surgery
* Use of acetaminophen within 24 hours of surgery
* Chronic users of analgesic medications, including taking opioid medications for more than 14 days in the last 3 months, or non-opioid pain medications more than 5 times per week
* History of, suspected, or known addiction to or abuse of drugs or alcohol within the past two years
* Current use of glucocorticosteroids or use of glucocorticoids within one month of enrollment into this study
* HIV infection or hepatitis
* Currently pregnant, nursing, or planning to become pregnant during the course of the study or within one month of study drug administration
* Any psychiatric, psychological, medical, or laboratory condition that the investigator feels makes the subject an inappropriate candidate for this clinical trial
* Subjects who have received another investigational drug within the longer of the last 30 days or 10 elimination half-lives
* Previous participation in a SKY0402 study
* Failure to pass drug and alcohol screen
B: 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.
C: Inclusion Criteria:

* Male or female, at least 18 years of age.
* Patients scheduled to undergo laparoscopic segmental colectomy with planned primary anastamosis, as defined by cecectomy, right hemicolectomy, resection of transverse colon, left hemicolectomy, or sigmoidectomy. (Note: patients who converted from a planned laparoscopic colectomy to an open colectomy were not eligible.)
* Ability to provide informed consent, adhere to study visit schedule, and complete all study assessments.

Exclusion Criteria:

* Patients with a history of hypersensitivity or idiosyncratic reactions or intolerance to any local anesthetic, opioid, or propofol.
* Patients who abuse alcohol or other drug substance.
* Patients with severe hepatic impairment.
* Patients currently pregnant or who may become pregnant during the course of the study or who are unwilling to use acceptable means of contraception for at least 1 month before and 1 month after dosing. Acceptable means of contraception include hormonal contraceptives (e.g., oral, injectable, implantable), effective barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, non-heterosexual lifestyle, or in a strictly monogamous relationship with a partner who has had a vasectomy.
* Patients with any psychiatric, psychological, or other condition that the Investigator feels may make the patient an inappropriate candidate for this clinical study.
* Participation in an EXPAREL study within the last 30 days.
* Patients who have received any investigational drug within 30 days prior to study drug administration, or planned administration of another investigational product or procedure during the patient's participation in this study.

In addition, a patient was ineligible if he or she met the following criteria during surgery:

* Patients who had any concurrent surgical procedure.
* Patients with unplanned multiple segmental resections of large intestine.
* Patients who converted from laparoscopic-assisted colectomy to traditional open colectomy.
* Patients who had unplanned, temporary or permanent colostomies, ileostomies, or the like placed.
* Patients who received intraoperative administration of opioids (other than fentanyl or analogs) or any other analgesic, local anesthetics, or anti-inflammatory agents.
* Patients who received Entereg.
D: Inclusion Criteria:

1. Male or female, greater than or equal to 18 and less than or equal to 75 years of age at the Screening Visit.
2. Female subjects only: Postmenopausal, surgically sterile, or willing to use acceptable means of contraception for at least 30 days after surgery including any of the following: hormonal contraceptives (e.g., oral, injectable, implantable starting at least 30 days before study drug administration), effective double-barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, nonheterosexual lifestyle, or a strictly monogamous relationship with a partner who has had a vasectomy.
3. Scheduled to undergo primary unilateral total knee arthroplasty (TKA) under general anesthesia.
4. American Society of Anesthesiology (ASA) Physical Class 1-3.
5. Able and willing to comply with all study visits and procedures.
6. Able to speak, read, and understand the language of the Informed Consent, study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments.
7. Willing and capable of providing written informed consent.

Exclusion Criteria:

1. Pregnancy, nursing, or planning to become pregnant during the study or within one month after dosing.
2. Use of any of the following medications within the times specified before surgery:

   * Long-acting opioid medication within 3 days.
   * Any opioid medication within 24 hours.
3. Concurrent, painful, physical condition or concurrent surgery that may require analgesic treatment in the postoperative period for pain that is not strictly related to the surgical site administered study treatment, and which may confound the postoperative assessments (e.g., significant pain from other joints, chronic neuropathic pain, concurrent contralateral TKA, concurrent foot surgery, etc.).
4. Body weight less than 50 kilograms (110 pounds) or morbid obesity.
5. Contraindication to any of the pain-control agents planned for postoperative use (e.g., acetaminophen, morphine, oxycodone, ketorolac).
6. Contraindication to epinephrine, such as concurrent administration of monoamine oxidase (MAO) inhibitors or antidepressants of amitriptyline or imipramine types, conditions where the production or exacerbation of tachycardia could prove fatal (e.g., poorly controlled thyrotoxicosis or severe heart disease), or any other pathological conditions that might be aggravated by the effects of epinephrine.
7. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.
8. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
9. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance.
10. Current or historical evidence of any clinically significant disease or condition, especially cardiovascular or neurological conditions that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postoperative course.
11. Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures, and expose the subject to an unreasonable risk as a result of participating in this clinical trial, such as: debilitating diseases, acute illnesses, hypotension, partial or complete conduction block, impaired cardiac function, untreated hypertension, advanced arteriosclerotic heart disease, cerebral vascular insufficiency, pre-existing abnormal neurological or neuromuscular disease (e.g., epilepsy, myasthenia gravis), advanced liver disease, severe renal impairment, advanced diabetes comorbid conditions associated with an immunocompromised status, such as blood dyscrasias, HIV/AIDS, or recent chemotherapy.

    In addition, the subject will be ineligible to receive study drug if he or she meets the following criteria during surgery:
12. Any clinically significant event or condition uncovered during surgery(e.g., excessive bleeding), which occurs before study drug administration, that might render the subject medically unstable or complicate the subject's postoperative course.

Answer: B