Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Active Control Study to Evaluate the Safety and Efficacy of a Single Intraoperative Administration of SKY0402 For Prolonged Postoperative Analgesia in Subject Undergoing Total Knee Arthroplasty
Brief Summary: The primary objective is to demonstrate that SKY0402 is superior when compared to bupivacaine HCl in the management of postoperative pain for patients undergoing total knee arthroplasty.


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. Male or female, ≥18 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 TKA under general or spinal anesthesia.
4. American Society of Anesthesiology (ASA) Physical Classification System class 1-4.
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 form, 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 being administered study drug (e.g., significant pain from other joints, chronic neuropathic pain, concurrent contralateral TKA, concurrent foot surgery, etc.), which have the potential to confound the postoperative study assessments.
4. Body weight less than 60 kilograms (\~132 pounds).
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 ergot-type drugs, monoamine oxidase (MAO) inhibitors or antidepressants of triptoline 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. 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 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 criterion 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.
C: Inclusion Criteria:

* Age ≥ 18 years at the Screening visit
* Scheduled to undergo primary unilateral first metatarsal osteotomy without hammertoe
* Female subjects must be surgically sterile or at least two years menopausal, or using an acceptable method of birth control. If of childbearing potential, have a documented negative blood or urine pregnancy test within 24 hours before surgery
* Clinical laboratory values less than or equal to twice the upper limit of normal or, if abnormal, deemed not clinically significant per the Investigator
* Ability to provide informed consent, adhere to the study visit schedule and complete all study assessments

Exclusion Criteria:

* Currently pregnant, nursing, or planning to become pregnant during the study or within one month after study drug administration
* Chronic user 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
* Use of any non-steroidal anti-inflammatory drug (NSAID) including selective COX-2 inhibitor within three days of surgery
* Use of acetaminophen within 24 hours of surgery
* Use of selective serotonin reuptake inhibitors (SSRIs), gabapentin, pregabalin (Lyrica), duloxetine (Cymbalta) within three days of surgery
* Current use of systemic glucocorticosteroids or use of systemic glucocorticoids within one month of enrollment into this study
* Peripheral neuropathy including diabetic neuropathy, chemotherapy-induced neuropathy, HIV neuropathy
* History of hepatitis
* History of, suspected, or known addiction to or abuse of drugs or alcohol within the past two years
* Failure to pass urine drug screen
* Current evidence of alcohol abuse (greater than 4 units of alcohol per day: 1 unit = ½ pint of beer, 1 glass of wine or 1 oz. of spirits)
* Evidence of peripheral ischemic disease
* Type I or Type II diabetes
* Current acute or chronic medical or major psychiatric disease that, in the opinion of the Investigator, would interfere with the evaluation of study drug efficacy or safety
* Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix
* Administration of an investigational drug within 30 days prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study
* Previous participation in a SKY0402 study
* Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures
* Current painful physical conditions or concurrent surgery other than bunionectomy that may require analgesic treatment (such as NSAID or opioid) in the postoperative period for pain that is not strictly related to the bunionectomy procedure and may confound the postoperative assessments
D: Inclusion Criteria:

* Male or female equal or greater than 18 years of age at Screening
* Female subjects: postmenopausal, surgically sterile, or willing to use acceptable means of contraception for at least 30 days after surgery, nonheterosexual lifestyle, or strictly monogamous relationship with a partner who has had a vasectomy.
* Scheduled to undergo 2-or3-column excisional hemorrhoidectomy
* American Society of Anesthesiology (ASA) Physical Class 1-4
* Able and willing to complete with all study visits and procedures
* Able to speak, read, and understand the language of all study forms and instruments used for collecting subject-reported outcomes to provide accurate study assessments
* Willing and capable of provide written informed consent.

Exclusion Criteria:

* Pregnant, nursing or planning to become pregnant during the study period
* Use of any long-acting opioid medication within 3 days of surgery or any opioid medication with 24 hours of surgery.
* Concurrent painful physical condition or concurrent surgery that may require analgesic treatment in the postoperative period for pain not strictly related to the procedure or that may interfere with study assessments.
* Single-column hemorrhoidectomy
* Body weight less than 50 kg (110 pounds)
* History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics, opioid medication, or any ingredient of the medications administered in this study (e.g., sulfites in Marcaine with epinephrine)
* contraindication to epinephrine
* contraindication to any of the pain-control agents planned for postoperative use
* Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug prior to study drug administration
* History of, known addiction, or abuse of illicit drugs, prescription medicines or alcohol within the past 2 years.
* Uncontrolled anxiety schizophrenic, or other psychiatric disorder that may interfere with study assessments or compliance.
* Significant medical conditions or laboratory results that 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.
* Any clinically significant event or condition uncovered during surgery
* A cumulative incision length less than 3 cm

Answer: B