ALGRX 4975 After Total Knee Replacement

• The subject (male or female) is aged 35 - 80 years. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to administration of study drug; must be nonlactating; and must be willing to use adequate and reliable contraception throughout the study.
• The subject is planned to undergo unilateral TKA.
• The subject is willing and able to understand the study procedures and the use of pain scales, and to communicate meaningfully with the study personnel.
• The subject is in good health and capable of undergoing TKA.
• The subject has signed the Informed Consent approved by the Institutional Review Board (IRB).

Exclusion Criteria:

• The subject has a laboratory test value outside the accepted range unless approved by the Sponsor.
• The subject is currently taking or has taken a chronic opioid (more than 30 consecutive days of daily use) for pain other than knee pain in the past two years.
• The use of capsaicin, opioids, bupivacaine, ropivacaine, muscle relaxants, or acetaminophen is contraindicated in this subject (e.g., significant history of allergic reactions or intolerance to these or related substances).
• The use of general anesthesia is contraindicated in this subject.
• The subject is taking central nervous system (CNS) active drugs such as benzodiazepines, tricyclic antidepressants, or selective serotonin reuptake inhibitors (SSRIs) for pain. These drugs are permitted for non-pain indications if the dose has been stable for at least 30 days. The use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen is permitted if stable over at least 30 days. The use of lorazepam and other sleep medications is permitted. Administration of ketorolac tromethamine (Toradol®) is permitted preoperatively, intraoperatively, and postoperatively no later than 8 PM on the day of surgery.
• The subject has a medical condition that, in the Investigator's opinion, could adversely impact the subject's participation or safety; conduct of the study; or interfere with the pain assessments, including fracture or active infection.
• The subject has diabetes mellitus and HbA1C > 9.5 or a history of prolonged uncontrolled diabetes.
• The subject has another painful physical condition that, in the opinion of the Investigator, may confound the assessments of postoperative pain or rehabilitation. The subject has a history of or current neuropathic pain condition.
• The subject is planned to undergo bilateral TKA.
• The subject has had arthroplasty (partial or total) of the index knee.
• The subject has a history of drug, prescription medicine or alcohol abuse within the past 2 years.
• The subject is taking an antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days
• The subject is taking any of the following medications: digoxin; all antiarrhythmics except beta-blockers; warfarin; theophylline preparations; aminoglycosides; anticonvulsants except benzodiazepines; and lithium.
• The subject has taken an investigational product within 3 months prior to the first dose of study drug (Visit 2), or is scheduled to receive an investigational product other than ALGRX 4975, while participating in the study.
• The subject has a known bleeding disorder or is taking agents affecting coagulation. Low dose aspirin is allowed as cardiac prophylaxis; NSAIDs, if stable for at least 30 days, are permitted; and deep venous thrombosis prophylaxis, of the surgeon's choice, is permitted postoperatively.
• The subject has previously participated in a clinical study with ALGRX 4975.