A Phase 2 Randomized Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Single Intrathecal Preoperative Administration of AYX1 Injection in Patients Undergoing Unilateral Total Knee Arthroplasty
Overview
- Phase
- Phase 2
- Intervention
- AYX1 Injection 660 mg/6 mL
- Conditions
- Post-surgical Pain
- Sponsor
- Adynxx, Inc.
- Enrollment
- 210
- Locations
- 9
- Primary Endpoint
- Mean pain with walking during the 15 meter walk test Day 7 to Day 28
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The objectives of this study are to evaluate the safety and analgesic efficacy of a single preoperative intrathecal administration of AYX1 Injection in patients undergoing unilateral total knee arthroplasty.
Detailed Description
This is a multi-center, Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of AYX1 Injection administered intrathecally before surgery in patients undergoing primary unilateral total knee arthroplasty (TKA). Subjects will be randomized on the day of surgery to receive either intrathecal AYX1 Injection or intrathecal placebo just prior to surgery. Study assessments will be conducted during the inpatient period through 48 hours; follow-up visits will be performed through Study Day 90.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Scheduled to undergo primary unilateral TKA with spinal anesthesia for painful osteoarthritis without congenital knee pathology
- •American Society of Anesthesiologists Physical Status Classification System ≤ 3
- •Medically stable as determined by the Investigator based on pre-study medical history, physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings
- •Body Mass Index of 18-45 kg/m2
- •Stable medical regimen for at least 1 week before randomization
- •Able to read and understand study instructions in English, and willing and able to comply with all study procedures
Exclusion Criteria
- •More than 2 other current focal areas of pain, any pain areas greater in intensity than the target knee, or any other active chronic pain conditions that would compromise operative knee pain evaluation
- •Inflammatory arthridities (e.g., rheumatoid arthritis, lupus, ankylosing spondylitis, psoriatic arthritis), with the exception of clinically stable/non-active gout that does not affect the knee and does not interfere with walking
- •Surgery in either knee within 3 months prior to randomization, or surgery in either knee greater than 3 months prior to randomization with residual symptoms that would interfere with post-TKA study assessments; use of cryoneurolysis (including Iovera) on the current operative knee region within the 6 months prior to randomization and/or at any time through the duration of the study
- •Planned use of general anesthesia or potent inhalational agents, peripheral nerve block (e.g., femoral nerve block), neuroaxial (intrathecal or epidural) opioids, preoperative extended release/long acting opioids, or any use of ketamine preoperatively and/or at any time through the duration of the study
- •Use of more than 40 mg per day (on average) of oral morphine or its equivalent within 1 month prior to randomization
- •Use of gabapentin or pregabalin within 1 week prior to randomization or planned use post-operatively through Day 28
- •Use of systemic corticosteroids (IV or oral) within 3 months prior to randomization through Day 28; planned use of intra-articular steroid injections in the operative knee from the time of randomization through Day 28
- •Current neurologic disorder, which could confound the assessment of pain (e.g., Parkinson's, Multiple Sclerosis)
- •Untreated or inadequately treated (in the opinion of the Investigator) active depression
- •Mini Mental State Exam score \< 24 at screening
Arms & Interventions
AYX1 Injection 660 mg/6 mL
Single Intrathecal (spinal) administration of AYX1 Injection (660 mg in 6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery.
Intervention: AYX1 Injection 660 mg/6 mL
Placebo Injection 6 mL
Single Intrathecal (spinal) administration of Placebo Injection (6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery
Intervention: Placebo Injection 6 mL
Outcomes
Primary Outcomes
Mean pain with walking during the 15 meter walk test Day 7 to Day 28
Time Frame: 7-28 days post-surgery
Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 15 meter walk test during the outpatient period from Day 7 to Day 28
Secondary Outcomes
- Total use of postoperative opioid medications (morphine equivalents) post-discharge to Day 90(post-hospital discharge through 90 days post-surgery)
- Percentage of subjects with NRS pain score ≥ 4 during the 15 meter walk at Day 90(at 90 days post-surgery)
- Mean pain rating (NRS) at rest Day 7 to Day 28(7-28 days post-surgery)