ALGRX 4975 After Total Knee Replacement
Condition: Arthroplasty, Replacement, Knee; Knee Injuries
MeSH terms: Knee Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      ALGRX 4975 or placebo will be dripped onto the cut muscles and soft tissues before the end of
      surgery for total replacement of the knee.

      Each subject will undergo a screening visit; a hospitalization, during which total
      replacement of the knee will be performed; and follow-up visits at 2, 6, and 12 weeks after
      surgery. In addition, once discharged, subjects will be contacted by telephone daily up to
      Day 14. 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 each morning at 8 AM ± 2 hours and each afternoon at 3
      PM ± 3 hours. 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.
    

Detailed description: 
      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.
    

Intervention name(s): ALGRX 4975
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Arthroplasty; Total knee arthroplasty; Capsaicin; Pain; Analgesia