Total Knee Arthroplasty (TKA) Study of HTX-011 in an Multimodal Analgesic Regimen (MMA) Regimen

A Phase 3b, Open-Label Study of HTX-011 as Part of a Scheduled Non-Opioid Multimodal Analgesic Regimen in Subjects Undergoing Total Knee Arthroplasty

Phase 3b, open-label single-arm study in which all subjects receive HTX-011 as part of a scheduled non-opioid MMA regimen.

Inclusion Criteria:

• Is scheduled to undergo primary unilateral TKA under spinal anesthesia.
• Has not previously undergone TKA in either knee.
• Has an American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
• Is able to walk at least 20 feet with 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 is at least 2 years post-menopausal; or is in a monogamous relationship with a partner who is surgically sterile; or using acceptable contraceptives.

Exclusion Criteria:

• Has a planned concurrent surgical procedure.
• Has other pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
• Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
• Using or expected to use Factor IX Complex or anti-inhibitor coagulant concentrates during the study.
• 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 with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
• 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 been administered any local anesthetic within 72 hours 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.
• Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
• 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.
• 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.
• Is currently undergoing treatment for hepatitis B, hepatitis C, or HIV.
• Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, might interfere with study assessments.
• Has acquired defective color vision or acute gastrointestinal ulcers, either of which could interfere with scheduled study medications.
• 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 nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
• Has undergone 3 or more surgeries within 12 months.
• Has a body mass index (BMI) >39 kg/m2.