Overview

PRF-110 is a viscous, yellowish clear oily solution of ropivacaine intended for administration into surgical sites to provide post-operative analgesia. The pharmacokinetic profile for PRF-110 suggests that its effect could last up to 72 hours. This is A Phase 3, Randomized, Double-Blind, Saline Placebo- and Active-Controlled, Multicenter Study to Evaluate the Analgesic Efficacy and Safety of Intra-operative Administration of PRF-110 Following Unilateral Bunionectomy

Eligibility

Inclusion Criteria:

Inclusion criteria:

        Subjects must meet all of the following criteria to be eligible for inclusion into the
        study:
          1. Able to provide written informed consent prior to any study procedures.
          2. Able to communicate clearly with the Investigators and study staff.
          3. Males and females aged 18 years or older.
          4. Scheduled for elective primary unilateral first metatarsal bunionectomy surgery
             (osteotomy and internal fixation) with no ancillary procedures.
          5. Female subjects must be surgically sterile; or at least 2 years postmenopausal; or
             have a monogamous partner who is surgically sterile; or practicing doublebarrier
             contraception; or practicing abstinence (must agree to use double-barrier
             contraception in the event of sexual activity); or using an insertable, injectable,
             transdermal, or combination oral contraceptive approved by the FDA for greater than
             two months prior to screening and commit to the use of an acceptable form of birth
             control for the duration of the study and for 30 days after completion of the study.
          6. Negative alcohol breath/saliva test and urine drug screen for drugs of abuse at
             Screening and at Baseline. Subjects with positive results on the alcohol breath/saliva
             test or urine drug screen at Screening, and/or prior to surgery, will not be allowed
             to proceed in the study unless the results can be explained by a current prescription
             or acceptable over-the-counter medication as determined by the Investigator. Note that
             for those subjects who test positive for tetrahydrocannabinol (THC), if they are
             willing to abstain from use or consumption of THC-containing products from Screening
             thru last Follow-up Visit, they may be allowed to participate in the study.
          7. American Society of Anesthesiologists (ASA) Physical Status of I or II (see Appendix,
             Section 14.1).
          8. Body Mass Index (BMI) ≤35.
        Exclusion Criteria:
        subject will be excluded from the study if any of the following criteria are met:
          1. Has clinically significant allergies to an opioid, unless has subsequently tolerated
             other opioids and, in the opinion of the Investigator, could tolerate a rescue drug
             containing oxycodone.
          2. Has a known or suspected allergy to any local anesthetic or to acetaminophen.
          3. Has a known or suspected history of alcohol, opiate or other drug abuse or dependence
             within 12 months prior to screening.
          4. Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to
             surgery through the end of the 72 -hour evaluation period.
          5. Has taken any analgesic or non-opioid pain medication other than acetaminophen (e.g.,
             NSAIDs, cyclooxygenase-2 [COX 2] inhibitors) within 12 hours prior to surgery or any
             aspirin-containing product within 7 days of the Baseline assessments. Aspirin up to
             325 mg once daily for cardiovascular prophylaxis is allowed.
          6. Has taken any opioid analgesics or used systemic steroids within 4 days of surgery.
          7. Has been using opiates or any non-steroidal anti-inflammatory drug chronically (more
             than 10 consecutive days) anytime over the past 3 months.
          8. Has used antipsychotics or antiepileptics within 30 days prior to surgery. Use of
             sedatives, hypnotics, antianxiety agents, and antidepressants (other than monoamine
             oxidase inhibitors [MAOIs]) are allowed if being used for a nonpain indication and at
             a stable dose within the previous 30 days.
          9. Has history of or positive test results for HIV or hepatitis B or C at Screening.
         10. Has any history of epilepsy, other than childhood febrile seizures, before the age of
             6.
         11. Has any history of psychosis, current clinically significant symptomatic psychiatric
             disorder, or a history of suicide attempt in the past 10 years.
         12. Has taken herbal agents or nutraceuticals (e.g., chapparal, comfrey, germander, jin bu
             huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) during any of the 7
             days prior to surgery that could potentially confound the analgesic response in the
             Investigator's opinion.
         13. Has transaminase levels > 2 x ULN, or bilirubin level > 1.5 x ULN (unless Gilbert's
             syndrome), or estimated glomerular filtration rate (eGFR) < 60 mL/min. Has poorly
             controlled diabetes with hemoglobin A1c >7.5%.
        15. Has any clinically significant condition including an acute or chronic painful physical
        restrictive condition or any other significant laboratory abnormality that would, in the
        opinion of the Investigator, confound study assessments or adversely affect subject safety.
        16. Has received another investigational drug within 30 days of scheduled surgery.