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

Study to Evaluate the Safety & Efficacy of a Single Intrathecal Pre-Operative Administration of AYX1 Injection at Two Dose Levels Compared to Placebo in Patients Undergoing Unilateral Total Knee Arthroplasty (TKA)

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.

Study Overview

• Status: Completed
• Conditions: Postsurgical Pain
• Intervention / Treatment: Drug: Placebo Injection; Drug: AYX1 Injection 110 mg; Drug: AYX1 Injection 330 mg

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Sheffield, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • Florida
    • Boynton Beach, Florida, United States
  • Pennsylvania
    • Altoona, Pennsylvania, United States
  • Texas
    • Houston, Texas, United States
    • Nassau Bay, Texas, United States
    • Odessa, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Vehicle) Injection; Single Intrathecal (spinal) administration of Placebo Injection just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: Placebo Injection; 3mL solution for intrathecal injection; Vehicle formulation designed to mimic AYX1 Injection (with no active drug)
Experimental: AYX1 Injection 110 mg; Single Intrathecal (spinal) administration of AYX1 Injection (110 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: AYX1 Injection 110 mg; 3mL solution for intrathecal injection with 110 mg of AYX1
Experimental: AYX1 Injection 330 mg; Single Intrathecal (spinal) administration of AYX1 Injection (330 mg) just prior to intrathecal administration of spinal anesthetic for knee surgery	Drug: AYX1 Injection 330 mg; 3mL solution for intrathecal injection with 330 mg of AYX1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 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 outpatient period up to Day 28	From hospital discharge to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		From hospital discharge to Day 28
Pain with 45 degrees of knee flexion	Mean pain rating on the Numerical Rating Scale (NRS) for 45 degrees active knee flexion	0-48 hours after surgery
Pain with 90 degrees of knee flexion	Mean pain rating on the Numerical Rating Scale (NRS) for 90 degrees active knee flexion	From 7 to 28 days after surgery

Other Outcome Measures

Outcome Measure	Time Frame
Brief Pain Inventory functional interference scores at Days 7, 14, 21, 28, and 42	7 to 42 days after surgery

Collaborators and Investigators

• Sponsor: Adynxx, Inc.
• Investigators: Study Director: Donald C Manning, MD, PhD, Adynxx, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: November 19, 2012
• First Submitted That Met QC Criteria: November 19, 2012
• First Posted (Estimate): November 22, 2012

Study Record Updates

• Last Update Posted (Estimate): January 27, 2015
• Last Update Submitted That Met QC Criteria: January 14, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Total knee replacement; Total knee arthroplasty; Postsurgical pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: ADYX-002