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

NCT01731730 | Completed Phase 2 DMC

• 1 other identifier: ADYX-002
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Postsurgical Pain

Keywords

Postsurgical pain; Total knee arthroplasty; Total knee replacement

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

  0-48 hours after surgery

• Pain with 90 degrees of knee flexion

  From 7 to 28 days after surgery

Other Outcomes (1)

• Brief Pain Inventory functional interference scores at Days 7, 14, 21, 28, and 42

  7 to 42 days after surgery

Study Arms (3)

Placebo (Vehicle) Injection

PLACEBO COMPARATOR

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

Drug: Placebo Injection

AYX1 Injection 110 mg

EXPERIMENTAL

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

AYX1 Injection 330 mg

EXPERIMENTAL

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

Interventions

Placebo Injection DRUG

3mL solution for intrathecal injection; Vehicle formulation designed to mimic AYX1 Injection (with no active drug)

Placebo (Vehicle) Injection

AYX1 Injection 110 mg DRUG

3mL solution for intrathecal injection with 110 mg of AYX1

AYX1 Injection 110 mg

AYX1 Injection 330 mg DRUG

3mL solution for intrathecal injection with 330 mg of AYX1

AYX1 Injection 330 mg

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adynxx, Inc.: lead

Study Sites (7)

Unknown Facility

Sheffield, Alabama, United States

Location

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Boynton Beach, Florida, United States

Location

Unknown Facility

Altoona, Pennsylvania, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Nassau Bay, Texas, United States

Location

Unknown Facility

Odessa, Texas, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Donald C Manning, MD, PhD

  Adynxx, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: January 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: November 1, 2013
• Last Updated: January 27, 2015

Record last verified: 2015-01

Locations

US (7)