Primary Outcome Measures:
- The daily average of the numerical rating scale (NRS) for pain with active range of motion of the operated knee at 8 AM ± 2 hours and at 3 PM ± 3 hours on Day 1, on Day 2, and on Days 1 through 2
Secondary Outcome Measures:
- The daily average of the numerical rating for pain with active range of motion of the operated knee at 8 AM ± 2 hours and at 3 PM ± 3 hours on Days 3 through 14, and Days 1 through 14
- The daily average of the numerical rating for pain during first ambulation in the morning and first ambulation after noon on Day 1, Day 2, Days 1 through 14, and Days 3 through 14
- Morphine sulfate that the subject self-administers for postoperative pain for each 12 hour period postoperatively starting at 8 AM on the day following surgery
- Time to first dose of supplemental pain medication (hydrocodone 7.5 mg/acetaminophen 500 mg) after self-administration of morphine sulfate is discontinued
- Number of tablets of hydrocodone 7.5 mg/acetaminophen 500 mg used during the first two postoperative weeks after total knee arthroplasty (TKA)
- The average quantity of hydrocodone 7.5 mg/acetaminophen 500 mg used during the first two postoperative weeks after surgery
- Pain and pain interference with activities at 2, 6, and 12 weeks using the Brief Pain Inventory-Short Form (BPI-SF)
- Effect of ALGRX 4975 on the use of assistive devices (cane, walker, wheelchair, bedside commode, or other assistive devices) at discharge, 2, 6, and 12 weeks
- Effect of ALGRX 4975 on active flexion range of motion of the operated knee, measured using a goniometer, at the 2 week postoperative visit
This is a multicenter, randomized, double-blind, placebo-controlled, study conducted in subjects undergoing unilateral TKA. Subjects will undergo a screening visit up to 28 days prior to surgery. A sufficient number of subjects will be enrolled to obtain at least 40 evaluable subjects. Upon enrollment, subjects will be randomized in a 1:1 ratio of ALGRX 4975 to placebo. Subjects will receive a femoral nerve block prior to induction of general anesthesia. Subjects will undergo total knee arthroplasty (TKA) under general anesthesia. Prior to closure of the surgical wound, a single dose of ALGRX 4975 5 mg in 60 mL or placebo will be instilled (dripped by syringe over approximately 1 minute) into the wound onto the cut muscles and soft tissues and allowed to dwell for 5 minutes. The Investigator will then inject bupivacaine 0.25% up to 40 mL into the area of the wound and cut muscles and close the wound by usual surgical procedures. Postoperative pain will be managed by morphine sulfate administered intravenously by patient controlled analgesia (PCA). Following discontinuation of the PCA pump, subjects will be provided with hydrocodone 7.5 mg/acetaminophen 500 mg for postoperative pain.
Each subject will undergo a screening visit; a hospitalization, during which TKA will be performed; and follow-up visits at 2, 6, and 12 weeks after surgery. Subjects will receive twice daily examinations while hospitalized for the TKA procedure. In addition, once discharged, subjects will be contacted by telephone daily up to Day 14, to remind them to complete pain and medication diaries, and then again at 4 weeks after surgery for follow-up. Subjects will complete pain and medication diaries during the first 2 weeks following surgery and will return these diaries at the 2 week visit.
Starting on the afternoon of Day 0 (the day of surgery), pain on active range of motion (ROM) of the operated knee will be measured using an 11 point numerical rating scale (NRS) each morning at 8 AM ± 2 hours and each afternoon at 3 PM ± 3 hours, not within one hour after physical therapy. In addition, if the subject ambulates, pain with ambulation will be measured during the first ambulation in the morning and during the first ambulation after noon. Subjects will complete the Brief Pain Inventory - Short Form (BPI-SF) preoperatively, and at the 2, 6, and 12 week visits. Subjects will be questioned regarding the use of assistive devices (cane, walker, wheelchair, bedside commode, or other assistive devices) at screening, at discharge, and at the 2, 6, and 12 week visits. The active ROM on flexion of the knee, measured using a goniometer, will be recorded at screening and at the 2 week visit. Sensory mapping of the knee will be performed at screening and at the 12 week visit.