Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia

Heron Therapeutics

Status and phase: Completed; Phase 2

Conditions: Postoperative Pain

Treatments: Drug: HTX-011; Drug: Ropivacaine; Drug: Bupivicaine HCl; Drug: Saline Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03015532

HTX-011-209

Details and patient eligibility

About

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.

Enrollment: 285 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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285 participants in 8 patient groups, including a placebo group

Cohort 1, Group 1: HTX-011

Experimental group

Description:

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

Treatment:

Drug: HTX-011

Cohort 1, Group 2: HTX-011

Experimental group

Description:

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

Treatment:

Drug: HTX-011

Cohort 1, Group 3: Saline Placebo

Placebo Comparator group

Description:

Saline placebo via injection

Treatment:

Drug: Saline Placebo

Cohort 1, Group 4: Bupivacaine HCI

Active Comparator group

Description:

Bupivacaine HCl without epinephrine, 125 mg via injection

Treatment:

Drug: Bupivicaine HCl

Cohort 2, Group 1: HTX-011

Experimental group

Description:

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

Treatment:

Drug: HTX-011

Cohort 2, Group 2: HTX-011 + Ropivacaine

Experimental group

Description:

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

Treatment:

Drug: Ropivacaine

Drug: HTX-011

Cohort 2, Group 3: Saline Placebo

Placebo Comparator group

Description:

Saline placebo via injection

Treatment:

Drug: Saline Placebo

Cohort 2, Group 4: Bupivacaine HCI

Active Comparator group

Description:

Bupivacaine HCl without epinephrine, 125 mg via injection

Treatment:

Drug: Bupivicaine HCl