A Phase 3 Study of F14 for Management of Pain Following Total Knee Replacement

Exclusion Criteria

• •Known allergy or hypersensitivity to active ingredient celecoxib, OR known allergy or hypersensitivity to sulfonamide antibiotics or sulfa containing drugs when an allergy to celecoxib is unknown
• •Unwilling or unable to discontinue use of nonsteroidal anti-inflammatory drugs (NSAIDs) at least 7 days before study surgery and for 6 weeks following study surgery
• •Unwilling or unable to discontinue use of medical or recreational marijuana or cannabidiol (CBD) at least 10 days before study surgery and for 3 months following study surgery
• •Unwilling or unable to discontinue use of pregabalin, gabapentin or other drugs for neuropathic pain at least 7 days prior to study surgery and for 3 months following study surgery
• •Unwilling or unable to discontinue opioid analgesics at least 7 days prior to surgery
• •Has an allergy or contraindication to opioids or NSAIDs or acetaminophen
• •Active or past infection in the index knee
• •Total or partial knee arthroplasty in the contralateral knee \< 6 months prior to study surgery
• •Knee surgery (including cruciate ligament, cartilage or osteotomy) other than simple arthroscopy in either knee in the last 12 months (excluding contralateral total or partial knee replacement)
• •Documented osteonecrosis within previous 12 months
• •Prior or current presence of hardware in index knee other than screws from previous ligament repair that do not require manipulation or removal for TKR surgery
• •Other planned major surgery within 12 months of study surgery
• •Concurrent painful physical condition that is unrelated to the study knee (e.g., back, shoulder or contralateral knee pain) that will require analgesic treatment, such as NSAIDs or opioids, during study follow-up
• •Current NRS pain intensity in the contralateral knee with a severity ≥ 4
• •Current or historical evidence of any clinically significant disease or condition, especially cardiovascular, pulmonary or neurological, that, in the opinion of the Investigator, may increase the risk of surgery or complicate or affect the subject's study follow-up
• •Suspected opioid abuse in the last 12 months with a score exceeding 5 on the DAST-10 questionnaire, and/or taking opioids ≥ 46 of the previous 90 days, and currently taking \>90 mg in morphine milligram equivalents (MME) at least 5 days per week in the month prior to screening.
• •History of alcohol abuse within previous 12 months (score of 4 on CAGE questionnaire)
• •Anxiety Sensitivity Index (ASI) score \>40
• •Fear of Pain Score (FPQ-III) score \>120
• •Uncontrolled depression, mood or anxiety disorder (score exceeding 14 on PHQ-9 questionnaire)
• •Participation or scheduled participation in another clinical study involving an investigational drug or device within one calendar month before screening or during study follow-up
• •Current medical diagnosis or patient-reported seizure disorder
• •Current peripheral neuropathy
• •History of complex regional pain syndrome (CRPS)
• •Diagnosis of clinically significant liver and/or renal abnormalities within previous 2 years
• •Diagnosis of diabetes with HbA1c ≥7
• •Current inflammatory arthritides (e.g., rheumatoid arthritis, lupus erythematosus, ankylosing spondylitis, psoriatic arthritis), or traumatic bone injuries within 12 months before scheduled surgery, except for clinically stable/non-active gout that does not affect the knee and does not interfere with walking
• •Treatment with immunosuppressants within one calendar month of intervention. Also, antipsychotics, anticholinergics, or anticonvulsants within one calendar month of intervention unless stable dosage established for \> one calendar month and does not plan to change during 3 month follow up
• •Diagnosis of skin disorders including psoriasis, vascular insufficiency ulcers, and chronic venous stasis
• •Subjects with sleep apnea associated with a history of postoperative delirium. If symptomatic sleep apnea is currently treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP), use must be continued post-operatively
• •History of coronary or vascular stent placed within 3 months
• •Had a malignancy in the last 12 months, except for non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix
• •Positive urine drug screen for disallowed medication pre-operatively on day of study surgery
• •Participation in active or pending personal injury or workers' compensation litigation related to index knee
• •Any reason based on investigator clinical judgment, that subject may be non-compliant with respect to study obligations or assessments