A Phase 2 Study to Evaluate the Safety & Efficacy of Two Dose/Volume Levels 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
- Postsurgical Pain
- Sponsor
- Adynxx, Inc.
- Enrollment
- 120
- Primary Endpoint
- Pain with walking during 5 meter walk test
- Status
- Completed
- Last Updated
- 10 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 at two dose/volume levels.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Scheduled to undergo primary unilateral TKA 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/neurological examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings
- •Body Mass Index of 18-40 kg/m2
- •Stable medical regimen for at least 1 month 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, none greater in intensity than the target knee and no 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
- •Operative arthroscopy in the surgical knee in the last 4 months (except for meniscal repair which will be no shorter than 6 months before randomization) or in the contralateral knee in the last 2 months (or 3 months for meniscal repair), or other prior surgery in either knee in the last 12 months, except for diagnostic arthroscopy
- •Planned use of any of the following for TKA: general anesthesia using potent inhalational agents, peripheral nerve block (i.e., femoral nerve block), neuroaxial (intrathecal or epidural) opioids postoperatively, or knee capsule injections
- •Received aspirin or any nonsteroidal anti-inflammatory drug (NSAID) prior to randomization within the washout period required by the surgical team for surgery with spinal anesthetic, or planned use of NSAIDS post-operatively through Day 28
- •Use of more than 20 mg per day (on average) of oral morphine or its equivalent within 1 month prior to randomization
- •Use of adjuvant analgesics for chronic pain control (e.g., gabapentin, pregabalin) within 2 weeks prior to randomization or planned use post-operatively through Day 28
- •Daily use of benzodiazepines in the 3 months prior to randomization (unless used for sleep and dosage will be consistent after surgery)
- •Use of systemic corticosteroids (does not include inhaled steroids) within 3 months or intra-articular steroid injections within 1 month prior to randomization, or planned use of either post-operatively through Day 28
- •Treatment with immunosuppressives, antipsychotics, anticholinergics, or anticonvulsants within 1 month of randomization, with the exception of aspirin for cardiac prophylaxis (as long as discontinued within 1 week of randomization)
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
AYX1 Injection 1100 mg / 10 mL
Single Intrathecal (spinal) administration of AYX1 Injection (1100 mg in 10 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery
Intervention: AYX1 Injection 1100 mg / 10 mL
Placebo Injection 10 mL
Single Intrathecal (spinal) administration of Placebo Injection (10 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery
Intervention: Placebo Injection 10 mL
Outcomes
Primary Outcomes
Pain with walking during 5 meter walk test
Time Frame: 0-48 hours after surgery
Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 5 meter walk test during the inpatient stay (0-48 hours)
Pain with walking during 15 meter walk test
Time Frame: Hospital Discharge to Day 28
Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 15 meter walk test during the outpatient period up to Day 28
Secondary Outcomes
- Pain with 45 degrees of knee flexion(0-48 hours after surgery)
- Pain with 90 degrees of knee flexion(Hospital discharge to Day 28)
- Total use of opioid medications (morphine equivalents) during hospital stay(0-48 hours after surgery)
- Total use of opioid medications (morphine equivalents) post-discharge to Day 28(Hospital Discharge to Day 28)