NCT03015532

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
285

participants targeted

Target at P75+ for phase_2 postoperative-pain

Timeline
Completed

Started Jan 2017

Typical duration for phase_2 postoperative-pain

Geographic Reach
1 country

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 6, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 10, 2017

Completed
3 days until next milestone

Study Start

First participant enrolled

January 13, 2017

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 20, 2018

Completed
26 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 16, 2018

Completed
3.5 years until next milestone

Results Posted

Study results publicly available

October 27, 2021

Completed
Last Updated

March 2, 2026

Status Verified

February 1, 2026

Enrollment Period

1.3 years

First QC Date

January 6, 2017

Results QC Date

June 11, 2021

Last Update Submit

February 10, 2026

Conditions

Keywords

kneeknee replacementarthroplastyjoint replacementknee pain

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • 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).

    72 hours

  • Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)

    72 hours

Study Arms (8)

Cohort 1, Group 1: HTX-011

EXPERIMENTAL

HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via instillation

Drug: HTX-011

Cohort 1, Group 2: HTX-011

EXPERIMENTAL

HTX-011 (bupivacaine/meloxicam), 200 mg/6 mg via injection and instillation (combination)

Drug: HTX-011

Cohort 1, Group 3: Saline Placebo

PLACEBO COMPARATOR

Saline placebo via injection

Drug: Saline Placebo

Cohort 1, Group 4: Bupivacaine HCI

ACTIVE COMPARATOR

Bupivacaine HCl without epinephrine, 125 mg via injection

Drug: Bupivicaine HCl

Cohort 2, Group 1: HTX-011

EXPERIMENTAL

HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation

Drug: HTX-011

Cohort 2, Group 2: HTX-011 + Ropivacaine

EXPERIMENTAL

HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via instillation; Ropivacaine, 50 mg via injection

Drug: HTX-011Drug: Ropivacaine

Cohort 2, Group 3: Saline Placebo

PLACEBO COMPARATOR

Saline placebo via injection

Drug: Saline Placebo

Cohort 2, Group 4: Bupivacaine HCI

ACTIVE COMPARATOR

Bupivacaine HCl without epinephrine, 125 mg via injection

Drug: Bupivicaine HCl

Interventions

HTX-011 (bupivacaine/meloxicam), via instillation

Cohort 1, Group 1: HTX-011Cohort 1, Group 2: HTX-011Cohort 2, Group 1: HTX-011Cohort 2, Group 2: HTX-011 + Ropivacaine

Saline placebo via injection

Cohort 1, Group 3: Saline PlaceboCohort 2, Group 3: Saline Placebo

Bupivacaine HCl without epinephrine

Cohort 1, Group 4: Bupivacaine HCICohort 2, Group 4: Bupivacaine HCI

Ropivacaine, via injection

Cohort 2, Group 2: HTX-011 + Ropivacaine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Unknown Facility

Mobile, Alabama, 36608, United States

Location

Unknown Facility

Sheffield, Alabama, 35660, United States

Location

Unknown Facility

Phoenix, Arizona, 85015, United States

Location

Unknown Facility

Phoenix, Arizona, 85023, United States

Location

Unknown Facility

La Jolla, California, 92037, United States

Location

Unknown Facility

Riverside, California, 92503, United States

Location

Unknown Facility

San Diego, California, 92103, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Miami, Florida, 33143, United States

Location

Unknown Facility

Miami, Florida, 33155, United States

Location

Unknown Facility

Tamarac, Florida, 33321, United States

Location

Unknown Facility

Las Vegas, Nevada, 89109, United States

Location

Unknown Facility

Columbus, Ohio, 43203, United States

Location

Unknown Facility

Columbus, Ohio, 43210, United States

Location

Unknown Facility

Dayton, Ohio, 45417, United States

Location

Unknown Facility

Bellaire, Texas, 77401, United States

Location

Unknown Facility

Houston, Texas, 77004, United States

Location

Unknown Facility

Houston, Texas, 77027, United States

Location

Unknown Facility

Houston, Texas, 77043, United States

Location

Unknown Facility

Plano, Texas, 75093, United States

Location

Unknown Facility

San Antonio, Texas, 78209, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

San Antonio, Texas, 78240, United States

Location

Unknown Facility

Webster, Texas, 77598, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Ropivacaine

Condition Hierarchy (Ancestors)

Postoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and SymptomsPainNeurologic ManifestationsSigns and Symptoms

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAmines

Results Point of Contact

Title
Tricia Mulford
Organization
Heron Therapeutics, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 6, 2017

First Posted

January 10, 2017

Study Start

January 13, 2017

Primary Completion

April 20, 2018

Study Completion

May 16, 2018

Last Updated

March 2, 2026

Results First Posted

October 27, 2021

Record last verified: 2026-02

Locations