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
• Genders Eligible for Study: All

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
• 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 NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores	Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded at rest (NRS-R).	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores	Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded at rest (NRS-R).	72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)		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 (ESTIMATE): January 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: knee; arthroplasty; knee pain; knee replacement; joint replacement
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine; Ropivacaine
• Other Study ID Numbers: HTX-011-209