Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: HTX-011; Saline Placebo; Bupivicaine HCl; Ropivacaine
Intervention description: HTX-011 (bupivacaine/meloxicam), via instillation; Saline placebo via injection; Bupivacaine HCl without epinephrine; Ropivacaine, via injection
Intervention MeSH terms: Bupivacaine; Ropivacaine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 285.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: knee; knee replacement; arthroplasty; joint replacement; knee pain

Summary:

      This is a Phase 2b, randomized, double-blind, saline placebo- and active-controlled,
      multicenter study in subjects undergoing primary unilateral total knee arthroplasty (TKA) to
      evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 administered
      via infiltration to the surgical site.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is scheduled to undergo primary unilateral TKA under general anesthesia.

          -  Has not previously undergone TKA in either knee.

          -  Has an American Society of Anesthesiologists Physical Status of I, II, or III.

          -  Is able to demonstrate motor function by performing a timed 20-meter walk unassisted,
             but with the optional use of a 4-legged walker for balance.

          -  Female subjects are eligible only if not pregnant, not lactating, not planning to
             become pregnant during the study, sterile; or using acceptable contraceptives.

        Exclusion Criteria:

          -  Has a planned concurrent surgical procedure (eg, bilateral TKA).

          -  Has a pre-existing concurrent acute or chronic painful/restrictive physical condition
             that may require analgesic treatment in the postoperative period for pain.

          -  Has a contraindication or a known or suspected history of hypersensitivity or
             idiosyncratic reaction to required study medications.

          -  Has known or suspected daily use of opioids for 7 or more consecutive days within the
             previous 6 months.

          -  Has taken NSAIDs within 10 days prior to the scheduled surgery.

          -  Has taken opioids within 24 hours prior to the scheduled surgery (3 days for
             long-acting).

          -  Has been administered bupivacaine within 5 days prior to the scheduled surgery.

          -  Has initiated treatment with medications within 1 month prior to study drug
             administration that can impact pain control.

          -  Has been administered systemic steroids within 5 half-lives or 10 days prior to
             administration of study drug.

          -  Has a medical condition such that, in the opinion of the Investigator, participating
             in the study would pose a health risk to the subject or confound the postoperative
             assessments.

          -  Has a known history of Hepatitis B, human immunodeficiency virus (HIV), or active
             Hepatitis C.

          -  Has uncontrolled anxiety, psychiatric, or neurological disorder that might interfere
             with study assessments.

          -  Has any chronic neuromuscular deficit of either femoral nerve function or thigh
             musculature. Has any chronic condition or disease that would compromise neurological
             or vascular assessments.

          -  Had a malignancy in the last year, with the exception of non-metastatic basal cell or
             squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.

          -  Has a known or suspected history of drug abuse, a positive drug screen on the day of
             surgery, or a recent history of alcohol abuse.

          -  Received an investigational product or device in a clinical trial within 30 days or
             within 5 elimination half lives.

          -  Has undergone 3 or more surgeries within 12 months.

          -  Has a body mass index (BMI) >38 kg/m2.