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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2020

Interventions

  • Drug: HTX-011
    • Dual-acting local anesthetic. Dose 1.
  • Drug: Ibuprofen
    • NSAID.
  • Drug: Acetaminophen
    • Analgesic.
  • Drug: Celecoxib
    • NSAID.
  • Drug: +/- Bupivacaine HCl
    • Local anesthetic.
  • Device: Luer Lock Applicator
    • Applicator for instillation.
  • Drug: HTX-011
    • Dual-acting local anesthetic. Dose 2.

Arms, Groups and Cohorts

  • Experimental: Cohort 1
    • HTX-011 + MMA
  • Experimental: Cohort 2
    • HTX-011 + MMA
  • Experimental: Cohort 3
    • HTX-011 + MMA
  • Experimental: Cohort 4
    • HTX-011 + MMA

Clinical Trial Outcome Measures

Primary Measures

  • Mean area under the curve (AUC) of the the visual analogue scale (VAS).
    • Time Frame: 12 through 48 hours

Secondary Measures

  • Mean AUC of VAS scores.
    • Time Frame: 72 hours
  • Mean AUC of the NRS of pain intensity at rest (NRS-R).
    • Time Frame: 72 hours
  • Proportion of subjects with severe pain.
    • Time Frame: 10 timepoints through 72 hours, and Day 11 and Day 29
  • Mean total postoperative opioid consumption (in IV morphine milligram equivalents [MME]).
    • Time Frame: 72 hours
  • Proportion of subjects who are opioid-free.
    • Time Frame: through 72 hours, and through Day 11
  • Proportion of subjects who are opioid-free through 72 hours who remain opioid-free through 72 hours who remain opioid-free.
    • Time Frame: 72 hours through Day 11
  • Median time to first opioid rescue medication.
    • Time Frame: 72 hours
  • Proportion of subjects who do not receive an opioid prescription at discharge.
    • Time Frame: 72 hours
  • Proportion of subjects who do not receive an opioid prescription between discharge and the Day 11 visit.
    • Time Frame: 72 hours through Day 11
  • Proportion of subjects achieving a score of “good” or better (>1) pain control based on Patient Global Assessment (PGA).
    • Time Frame: 24 hours, 48 hours, 72 hours, Day 11
  • Median time to first ambulation postsurgery.
    • Time Frame: 72 hours
  • Proportion of subjects unable to participate in each rehabilitation session because of pain.
    • Time Frame: 72 hours
  • Proportion of subjects who first achieve an MPADSS score ≥9.
    • Time Frame: 10 timepoints through 72 hours
  • Proportion of subjects who are discharged home vs to a skilled nursing facility.
    • Time Frame: 72 hours
  • Mean overall benefit of analgesia score (OBAS).
    • Time Frame: 24 hours, 48 hours, 72 hours, Day 11
  • Mean total TSQM-9 score
    • Time Frame: 72 hours through Day 11
    • Treatment Satisfaction Questionnaire for Medication (9-question)
  • Maximum concentration (Cmax)
    • Time Frame: 72 hours
  • Time of occurrence of maximum concentration (Tmax)
    • Time Frame: 72 hours

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Heron Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Chris Storgard, MD, (858) 251-4452, cstorgard@herontx.com

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