| Eligibility |
Inclusion Criteria:
1. Written consent to participate in the study
2. Be willing and able to complete study procedures and pain scales, follow instructions
and communicate meaningfully in English with study personnel, and return for
outpatient follow-up visits as required.
3. Male or female =18 to =65 years of age, inclusive
4. Planning to undergo an elective primary unilateral, distal, first metatarsal
bunionectomy with osteotomy and internal fixation, without collateral procedure or
additional surgeries, to be performed under Monitored Anesthesia Care (MAC) and be
eligible to receive a popliteal sciatic nerve block
5. Classified as either ASA 1 or ASA 2 by the American Society of Anesthesiologists
Physical Status Classification System (Appendix 1).
6. Has a BMI of =18 to = 35 kg/m2.
7. Willing to washout from all prohibited medications for the longer of 14 days or five
half-lives prior to dosing, and abstain from those medications through the end of
study (Appendix 5).
8. If a male, unless he has a same sex partner, be either sterile (surgically or
biologically) or commit to an acceptable method of birth control while participating
in the study.
9. If a woman of childbearing potential (WOCBP), must meet all of the following:
- Not be pregnant (WOCBP must have a negative serum pregnancy test at screening and
negative urine pregnancy test before surgery);
- Not plan to become pregnant or to breast feed during the study; and
- Be surgically sterile (at least one year post total hysterectomy, bilateral
oophorectomy or bilateral tubal ligation) or at least one year post-menopausal,
have a monogamous partner who is surgically sterile, have a same sex partner, or
(one of the following must apply):
- is practicing double-barrier contraception
- is practicing abstinence (must agree to use double-barrier contraception in
the event of sexual activity)
- is using a non-hormonal contraceptive approved by the FDA for at least 2
months prior to screening and commits to the use of an acceptable form of
birth control while participating in the study..
Exclusion Criteria:
1. Has a concurrent painful condition, other than bunion-related pain, that may require
analgesic treatment during the study period or may confound post-surgical pain
assessments.
2. Has an active skin disease or other clinically significant abnormality at the
anticipated site of surgery or nerve block insertion site that could interfere with
the planned surgery.
3. Has had previous bunionectomy or other surgical procedure on the index foot that could
impact the current bunion surgery.
4. Has any clinically significant cardiac, respiratory, neurological, immunological,
hematological, or renal disease or any other condition that, in the opinion of the
investigator, could compromise the subject's welfare, ability to communicate with the
study staff, or otherwise contraindicate study participation.
5. Has a known history of allergic reaction or clinically significant intolerance to
acetaminophen, aspirin, opioids, or any NSAIDs; history of NSAID-induced bronchospasm
(subjects with the triad of asthma, nasal polyps, and chronic rhinitis are at greater
risk for bronchospasm and should be considered carefully); or hypersensitivity,
allergy, or significant reaction to any other drugs used in the study, including
anesthetics and antibiotics that may be required on the day of surgery.
6. Has known or suspected daily use of opioids for 7 or more consecutive days within the
previous 6 months.
7. Has taken any opioids, NSAIDS, or acetaminophen within 3 days prior to the scheduled
surgery. Low dose aspirin (<100 mg) for cardiovascular protection is acceptable.
8. Has initiated treatment with any of the following medications within 30 days prior to
study medication administration or is taking any of these medications to control pain:
selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors,
gabapentin, pregabalin, or cyclooxygenase-2 inhibitors. (Note: If a subject is taking
one of these medications for a reason other than pain control, the subject must be on
a stable scheduled dose [i.e., not "as needed"] for at least 1 month prior to study
medication administration.)
9. Within the 14 days prior to surgery, be taking parenteral or oral corticosteroids
(steroid inhalers for allergy or asthma treatment, topical steroids for a
non-clinically significant skin condition not involving the area of surgery, or
ophthalmic steroids are permissible).
10. Is currently receiving antianginal therapy
11. Has a known or suspected history of alcoholism or drug abuse or misuse within 1 year
of screening or evidence of opioid tolerance or physical dependence before dosing with
the study medication.
12. Has positive results on the alcohol test (breath or saliva) indicative of alcohol
abuse or urine drug screen (UDS) indicative of illicit drug use at screening, and/or
prior to surgery. Note that for those subjects have a history of, or who test positive
for tetrahydrocannabinol (THC), if they are willing to abstain from use or consumption
of THC-containing products from 14 days prior to surgery to Day 85, they may be
allowed to participate in the study. Additionally, it may be permissible for the
subject to participate if the results of the UDS can be explained by a current
prescription or acceptable over-the-counter medication as determined by the
investigator at screening and/or prior to surgery.
13. Has significant difficulties swallowing tablets or is unable to tolerate oral
medication.
14. Has received any investigational drug or device or investigational therapy within the
last 30 days.
15. Has a history of a clinically significant (in the investigator's opinion) GI event
within 6 months before screening or has any history of peptic or gastric ulcers or GI
bleeding.
16. Has a surgical or medical condition of the GI or renal system that might significantly
alter the absorption, distribution, or excretion of any drug substance.
17. Is considered by the investigator to be an unsuitable candidate to receive the study
medication for any reason (including, but not limited to, the risks described as
precautions, warnings, and contraindications in the current version of the IB).
18. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been
diagnosed with cancer within 2 years before screening (excluding squamous or basal
cell carcinoma of the skin that has been clinically stable and/or fully excised in a
curative procedure).
19. Has significant renal disease, as indicated by clinical laboratory assessment
(creatinine > 1.9 mg/dL).
20. Has significant hepatic disease, as indicated by clinical laboratory assessment
(results = 2 times the upper limit of normal for any liver function test (LFT),
including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and
lactate dehydrogenase (LDH)).
21. Has a known history of seizure disorder, a family history of seizures, or previous
head trauma.
22. Has loss of sensation in extremities or significant peripheral neuropathy.
23. Laboratory evidence of infection with HIV, positive test for HBsAg, or positive
serology for hepatitis C virus (HCV) with positive test for HCV RNA.
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