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

This is a Phase 3, randomized, double blind, multicenter study to evaluate the analgesic efficacy and safety of a single intra-articular dose of F14 (625 mg sustained release celecoxib) administered concurrent with multimodal analgesia in patients undergoing total knee replacement surgery, compared to multimodal analgesia alone.

Inclusion Criteria:Male and/or females indicated for primary, unilateral total knee replacement (TKR)Between 45-80 years of age inclusive at the time of signing the informed consentCapable of giving signed informed consent and complying with requirements and restrictions listed in the informed consent form (ICF) and in this protocolBody Mass Index (BMI) ≤ 40 kg/m2Medically stable as determined by the Investigator, based on physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings, as well as medical history from patient and pre-study source documents from other care providersAbsence of moderate to severe fixed flexion deformityAbsence of moderate to severe varus or valgus deformityMinimum pre-operative flexion arc of 100 degreesAbsence of steroid, hyaluronic acid, platelet rich plasma, or any other type of therapeutic injection(s) in the index knee within 3 months before scheduled surgeryAmerican Society of Anesthesiologists Physical Status Classification System (ASA-PSC) score ≤ 3Females of childbearing potential with a negative serum pregnancy test at screening, or males that have a partner who is a woman of child-bearing potential (WOCBP), who agree to employ adequate birth control measures for the full duration of the study.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 unknownUnwilling or unable to discontinue use of nonsteroidal anti-inflammatory drugs (NSAIDs) at least 7 days before study surgery and for 6 weeks following study surgeryUnwilling 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 surgeryUnwilling 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 surgeryUnwilling or unable to discontinue opioid analgesics at least 7 days prior to surgeryHas an allergy or contraindication to opioids or NSAIDs or acetaminophenActive or past infection in the index kneeTotal or partial knee arthroplasty in the contralateral knee < 6 months prior to study surgeryKnee 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 monthsPrior or current presence of hardware in index knee other than screws from previous ligament repair that do not require manipulation or removal for TKR surgeryOther planned major surgery within 12 months of study surgeryConcurrent 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-upCurrent NRS pain intensity in the contralateral knee with a severity ≥ 4Current 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-upSuspected 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 >40Fear of Pain Score (FPQ-III) score >120Uncontrolled 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-upCurrent medical diagnosis or patient-reported seizure disorderCurrent peripheral neuropathyHistory of complex regional pain syndrome (CRPS)Diagnosis of clinically significant liver and/or renal abnormalities within previous 2 yearsDiagnosis of diabetes with HbA1c ≥7Current 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 walkingTreatment 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 upDiagnosis of skin disorders including psoriasis, vascular insufficiency ulcers, and chronic venous stasisSubjects 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-operativelyHistory of coronary or vascular stent placed within 3 monthsHad 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 cervixPositive urine drug screen for disallowed medication pre-operatively on day of study surgeryParticipation in active or pending personal injury or workers' compensation litigation related to index kneeAny reason based on investigator clinical judgment, that subject may be non-compliant with respect to study obligations or assessments