Study to Evaluate Safety/Efficacy of a Single Pre-Op Dose of AYX1 Injection to Treat Pain After Knee Replacement Surgery

Adynxx

Status and phase: Completed; Phase 2

Conditions: Postsurgical Pain

Treatments: Drug: AYX1 Injection 110 mg; Drug: AYX1 Injection 330 mg; Drug: Placebo Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT01731730

ADYX-002

Details and patient eligibility

About

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.

Enrollment: 102 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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102 participants in 3 patient groups, including a placebo group

Placebo (Vehicle) Injection

Placebo Comparator group

Description:

Single Intrathecal (spinal) administration of Placebo Injection just prior to intrathecal administration of spinal anesthetic for knee surgery

Treatment:

Drug: Placebo Injection

AYX1 Injection 110 mg

Experimental group

Description:

Single Intrathecal (spinal) administration of AYX1 Injection (110 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery

Treatment:

Drug: AYX1 Injection 110 mg

AYX1 Injection 330 mg

Experimental group

Description:

Single Intrathecal (spinal) administration of AYX1 Injection (330 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery

Treatment:

Drug: AYX1 Injection 330 mg