Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia

A Phase 2b, Randomized, Double-Blind, Saline Placebo- and Active-Controlled, Multicenter Study of HTX-011 Via Infiltration for Postoperative Analgesia in Subjects Undergoing Total Knee Arthroplasty

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: HTX-011; Drug: Saline Placebo; Drug: Bupivicaine HCl; Drug: Ropivacaine

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
    • Sheffield, Alabama, United States, 35660
  • Arizona
    • Phoenix, Arizona, United States, 85015
    • Phoenix, Arizona, United States, 85023
  • California
    • La Jolla, California, United States, 92037
    • Riverside, California, United States, 92503
    • San Diego, California, United States, 92103
  • Florida
    • Miami, Florida, United States, 33136
    • Miami, Florida, United States, 33155
    • Miami, Florida, United States, 33143
    • Tamarac, Florida, United States, 33321
  • Nevada
    • Las Vegas, Nevada, United States, 89109
  • Ohio
    • Columbus, Ohio, United States, 43210
    • Columbus, Ohio, United States, 43203
    • Dayton, Ohio, United States, 45417
  • Texas
    • Bellaire, Texas, United States, 77401
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77027
    • Houston, Texas, United States, 77043
    • Plano, Texas, United States, 75093
    • San Antonio, Texas, United States, 78240
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78209
    • Webster, Texas, United States, 77598

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1, Group 1: HTX-011; HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via instillation	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), via instillation
Experimental: Cohort 1, Group 2: HTX-011; HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via injection and instillation (combination)	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), via instillation
Placebo Comparator: Cohort 1, Group 3: Saline Placebo; Saline placebo via injection	Drug: Saline Placebo; Saline placebo via injection
Active Comparator: Cohort 1, Group 4: Bupivacaine HCI; Bupivacaine HCl without epinephrine, 125 mg via injection	Drug: Bupivicaine HCl; Bupivacaine HCl without epinephrine
Experimental: Cohort 2, Group 1: HTX-011; HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), via instillation
Experimental: Cohort 2, Group 2: HTX-011 + Ropivacaine; HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation; Ropivacaine, 50 mg via injection	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), via instillation; Drug: Ropivacaine; Ropivacaine, via injection
Placebo Comparator: Cohort 2, Group 3: Saline Placebo; Saline placebo via injection	Drug: Saline Placebo; Saline placebo via injection
Active Comparator: Cohort 2, Group 4: Bupivacaine HCI; Bupivacaine HCl without epinephrine, 125 mg via injection	Drug: Bupivicaine HCl; Bupivacaine HCl without epinephrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48).	Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-48 is 0-480.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)		72 hours
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 72 Hours Postsurgery (AUC0-72).	Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720.	72 hours

Collaborators and Investigators

• Sponsor: Heron Therapeutics

Publications and helpful links

General Publications

• Lachiewicz PF, Lee GC, Pollak RA, Leiman DG, Hu J, Sah AP. HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial. J Arthroplasty. 2020 Oct;35(10):2843-2851. doi: 10.1016/j.arth.2020.05.044. Epub 2020 May 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2017
• Primary Completion (Actual): April 20, 2018
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: January 6, 2017
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimated): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: knee; arthroplasty; knee pain; knee replacement; joint replacement
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Ropivacaine
• Other Study ID Numbers: HTX-011-209