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

• ClinicalTrials.gov Identifier: NCT03974932
• Recruitment Status: Completed
• First Posted: June 5, 2019
• Last Update Posted: March 9, 2021
• Sponsor: Heron Therapeutics
• Information provided by (Responsible Party): Heron Therapeutics

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Analgesia	Drug: HTX-011; Drug: Ibuprofen; Drug: Acetaminophen; Drug: Celecoxib; Drug: +/- Bupivacaine HCl; Device: Luer Lock Applicator	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 5, 2019
• Actual Primary Completion Date: December 7, 2020
• Actual Study Completion Date: January 7, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; HTX-011 + MMA	Drug: HTX-011; Dual-acting local anesthetic. Dose 1.; Drug: Ibuprofen; NSAID.; Drug: Acetaminophen; Analgesic.; Drug: Celecoxib; NSAID.; Device: Luer Lock Applicator; Applicator for instillation.
Experimental: Cohort 2; HTX-011 + MMA	Drug: HTX-011; Dual-acting local anesthetic. Dose 1.; Drug: Ibuprofen; NSAID.; Drug: Acetaminophen; Analgesic.; Drug: Celecoxib; NSAID.; Device: Luer Lock Applicator; Applicator for instillation.
Experimental: Cohort 3; HTX-011 + MMA	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.
Experimental: Cohort 4; HTX-011 + MMA	Drug: HTX-011; Dual-acting local anesthetic. Dose 1.; Drug: Ibuprofen; NSAID.; Drug: Acetaminophen; Analgesic.; Device: Luer Lock Applicator; Applicator for instillation.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Mean AUC of VAS scores. [ Time Frame: 72 hours ]
2. Mean AUC of the NRS of pain intensity at rest (NRS-R). [ Time Frame: 72 hours ]
3. Proportion of subjects with severe pain. [ Time Frame: 10 timepoints through 72 hours, and Day 11 and Day 29 ]
4. Mean total postoperative opioid consumption (in IV morphine milligram equivalents [MME]). [ Time Frame: 72 hours ]
5. Proportion of subjects who are opioid-free. [ Time Frame: through 72 hours, and through Day 11 ]
6. 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 ]
7. Median time to first opioid rescue medication. [ Time Frame: 72 hours ]
8. Proportion of subjects who do not receive an opioid prescription at discharge. [ Time Frame: 72 hours ]
9. Proportion of subjects who do not receive an opioid prescription between discharge and the Day 11 visit. [ Time Frame: 72 hours through Day 11 ]
10. 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 ]
11. Median time to first ambulation postsurgery. [ Time Frame: 72 hours ]
12. Proportion of subjects unable to participate in each rehabilitation session because of pain. [ Time Frame: 72 hours ]
13. Proportion of subjects who first achieve an MPADSS score ≥9. [ Time Frame: 10 timepoints through 72 hours ]
14. Proportion of subjects who are discharged home vs to a skilled nursing facility. [ Time Frame: 72 hours ]
15. Mean overall benefit of analgesia score (OBAS). [ Time Frame: 24 hours, 48 hours, 72 hours, Day 11 ]
16. Mean total TSQM-9 score [ Time Frame: 72 hours through Day 11 ]
    Treatment Satisfaction Questionnaire for Medication (9-question)
17. Maximum concentration (Cmax) [ Time Frame: 72 hours ]
18. Time of occurrence of maximum concentration (Tmax) [ Time Frame: 72 hours ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Helen Keller Hospital

Sheffield, Alabama, United States, 35660

United States, Florida

Phoenix Clinical Research, LLC

Tamarac, Florida, United States, 33321

United States, Ohio

Midwest Clinical Research Center, LLC

Dayton, Ohio, United States, 45417

United States, Texas

First Surgical Hospital

Bellaire, Texas, United States, 77401

Plano Surgical Hospital

Plano, Texas, United States, 75093

Endeavor Clinical Trials, LLC.

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Heron Therapeutics

More Information

• Responsible Party: Heron Therapeutics
• ClinicalTrials.gov Identifier: NCT03974932
• Other Study ID Numbers: HTX-011-306
• First Posted: June 5, 2019
• Last Update Posted: March 9, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Heron Therapeutics:

total knee arthroplasty; postoperative pain; multimodal analgesia

Additional relevant MeSH terms:

Acetaminophen; Ibuprofen; Celecoxib; Bupivacaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cyclooxygenase 2 Inhibitors