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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Adynxx, Inc.
ClinicalTrials.gov Identifier:
NCT01731730
First received: November 19, 2012
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Postsurgical Pain
Drug: Placebo Injection
Drug: AYX1 Injection 110 mg
Drug: AYX1 Injection 330 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Adynxx, Inc.:

Primary Outcome Measures:
  • Pain with walking during 5 meter walk test [ Time Frame: 0-48 hours after surgery ] [ Designated as safety issue: No ]
    Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 5 meter walk test during inpatient stay 0-48 hours

  • Pain with walking during 15 meter walk test [ Time Frame: From hospital discharge to Day 28 ] [ Designated as safety issue: No ]
    Mean pain rating on the Numerical Rating Scale (NRS) with walking during the 15 meter walk test during outpatient period up to Day 28


Secondary Outcome Measures:
  • Total use of opioid medications (morphine equivalents) during hospital stay [ Time Frame: 0-48 hours after surgery ] [ Designated as safety issue: No ]
  • Total use of opioid medications (morphine equivalents) post-discharge to Day 28 [ Time Frame: From hospital discharge to Day 28 ] [ Designated as safety issue: No ]
  • Pain with 45 degrees of knee flexion [ Time Frame: 0-48 hours after surgery ] [ Designated as safety issue: No ]
    Mean pain rating on the Numerical Rating Scale (NRS) for 45 degrees active knee flexion

  • Pain with 90 degrees of knee flexion [ Time Frame: From 7 to 28 days after surgery ] [ Designated as safety issue: No ]
    Mean pain rating on the Numerical Rating Scale (NRS) for 90 degrees active knee flexion


Other Outcome Measures:
  • Brief Pain Inventory functional interference scores at Days 7, 14, 21, 28, and 42 [ Time Frame: 7 to 42 days after surgery ] [ Designated as safety issue: No ]

Enrollment: 102
Study Start Date: January 2013
Study Completion Date: November 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01731730

Locations
United States, Alabama
Sheffield, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
United States, Florida
Boynton Beach, Florida, United States
United States, Pennsylvania
Altoona, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
Nassau Bay, Texas, United States
Odessa, Texas, United States
Sponsors and Collaborators
Adynxx, Inc.
Investigators
Study Director: Donald C Manning, MD, PhD Adynxx, Inc.
  More Information

No publications provided

Responsible Party: Adynxx, Inc.
ClinicalTrials.gov Identifier: NCT01731730     History of Changes
Other Study ID Numbers: ADYX-002
Study First Received: November 19, 2012
Last Updated: November 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Adynxx, Inc.:
Postsurgical pain
Total knee arthroplasty
Total knee replacement

ClinicalTrials.gov processed this record on July 26, 2014