Study to Evaluate Safety/Efficacy of a Single Pre-Op Dose... | NCT02081703

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
AYX1 Injection 660 mg / 6 mL	Experimental	Single Intrathecal (spinal) administration of AYX1 Injection (660 mg in 6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: AYX1 Injection 660 mg / 6 mL
Placebo Injection 6 mL	Placebo Comparator	Single Intrathecal (spinal) administration of Placebo Injection (6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: Placebo Injection 6 mL
AYX1 Injection 1100 mg / 10 mL	Experimental	Single Intrathecal (spinal) administration of AYX1 Injection (1100 mg in 10 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: AYX1 Injection 1100 mg / 10 mL
Placebo Injection 10 mL	Placebo Comparator	Single Intrathecal (spinal) administration of Placebo Injection (10 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: Placebo Injection 10 mL

Name	Type	Description	Arm Group Labels	Other Names
AYX1 Injection 660 mg / 6 mL	Drug	6 mL solution for intrathecal injection with 660 mg of AYX1	AYX1 Injection 660 mg / 6 mL

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pain with walking during 5 meter walk test	Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 5 meter walk test during the inpatient stay (0-48 hours)	0-48 hours after surgery
Pain with walking during 15 meter walk test	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	Hospital Discharge to Day 28

Secondary Outcomes

Measure	Description	Time Frame
Pain with 45 degrees of knee flexion	Mean pain rating on the Numerical Rating Scale (NRS) for 45 degrees passive knee flexion during the inpatient stay	0-48 hours after surgery
Pain with 90 degrees of knee flexion

Other Outcomes

Measure	Description	Time Frame
Percentage of subjects achieving 90 degrees of knee flexion	Percentage of subjects achieving 90 degrees of active knee flexion in the operative knee at Discharge through Day 42	Hospital discharge to Day 42

Eligibility Module

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)
Current neurologic disorder, which could confound the assessment of pain (e.g., 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
Severe pulmonary disease; if symptomatic sleep apnea is currently treated with continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BIPAP), use must be continued postoperatively at least during the inpatient period. Patients with sleep apnea associated with a history of postoperative delirium are excluded.
Current evidence of alcohol abuse or history of alcohol-related complications within 1 year of randomization including, but not limited to, alcoholic withdrawal seizures, hallucinations, delirium tremens or detoxification treatment
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
Previous participation in any study involving AYX1 Injection

Facility	Status	City	State	ZIP	Country	Contacts
		Sheffield	Alabama		United States

ID	Term
D011183	Postoperative Complications
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms