study to evaluate safety/efficacy of a single pre-op dose of ayx1 injection to treat pain after knee replacement surgery

Conditions: Postsurgical Pain

Summary: the objectives of this proof of concept study are to evaluate the safety and preventive analgesic efficacy of a single preoperative intrathecal administration of ayx1 injection in patients undergoing unilateral total knee arthroplasty.


Eligibility criteria:
inclusion criteria: * scheduled to undergo primary unilateral tka for painful osteoarthritis * 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 lab tests, and 12-lead ecg findings * body mass index of 18-40 kg/m2 * stable medical regimen for ≥ 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 (i.e., rheumatoid arthritis, lupus, ankylosing spondylitis, psoriatic arthritis, gout) * operative arthroscopy in the surgical knee in the last 6 months, 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 endotracheal anesthesia (geta), peripheral nerve block (i.e., femoral nerve block), neuroaxial (intrathecal or epidural) opioids postoperatively, or knee capsule injections * received aspirin within 1 week of randomization, or any nonsteroidal anti-inflammatory drug (nsaid) within 5 half-lives prior to randomization, 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 (i.e., gabapentin, pregabalin) during the month 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-op through day 28 * treatment with antibiotics or antivirals (exception: topical treatments), immunosuppressives, antipsychotics, anticholinergics, or anticonvulsants within 1 month of randomization, with the exception of prescribed pre-surgical prophylactic antibiotics, and aspirin for cardiac prophylaxis (as long as discontinued within 1 week of randomization * current neurologic disorder, which could confound the assessment of pain (i.e., parkinson's, multiple sclerosis) * current active depression symptoms * has had a change in dose or regimen of ssris or snris for depression within 1 month of randomization * mini mental state exam score \< 24 at screening * current history of insulin dependent diabetes mellitus, or autoimmune conditions * severe chronic obstructive or restrictive pulmonary disease, current diagnosis of obstructive sleep apnea documented by a sleep laboratory study, or current home use of continuous positive airway pressure (cpap) or bi-level positive airway pressure (bipap) * current evidence of alcohol abuse or history of alcohol-related complications within 1 year of randomization * known or suspected history of illicit drug abuse within 1 year before randomization, current or planned use of medical marijuana, or history of opioid dependence within 2 years before randomization * any malignancy within the past year, with the exception of basal cell carcinoma or uncomplicated or stable skin cancers documented to not require further or immediate treatment * women who are pregnant or nursing

Keywords: postsurgical pain total knee arthroplasty total knee replacement