Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia

Phase 2

Completed

• Conditions: Postoperative Pain
• Interventions: Drug: HTX-011; Drug: Saline Placebo; Drug: Bupivicaine HCl; Drug: Ropivacaine

• Registration Number: NCT03015532
• Lead Sponsor: Heron Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-01-06
• Study First Submitted QC: 2017-01-06
• Study First Posted: 2017-01-10
• Study Start: 2017-01-13
• Primary Completion: 2018-04-20
• Study Completion: 2018-05-16
• Disposition First Submitted: 2018-06-08
• Disposition First Submitted QC: 2018-06-08
• Disposition First Posted: 2018-06-12
• Results First Submitted: 2021-06-11
• Results First Submitted QC: 2021-09-29
• Results First Posted: 2021-10-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 285

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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).	48 hours	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.

Secondary Outcome Measures

Name	Time	Method
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	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.
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)	72 hours