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

NCT ID: NCT01731730

Last Updated: 2015-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2013-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo (Vehicle) Injection

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

Group Type: PLACEBO_COMPARATOR

Placebo Injection

Intervention Type: DRUG

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

AYX1 Injection 110 mg

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

Group Type: EXPERIMENTAL

AYX1 Injection 110 mg

Intervention Type: DRUG

3mL solution for intrathecal injection with 110 mg of AYX1

AYX1 Injection 330 mg

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

Group Type: EXPERIMENTAL

AYX1 Injection 330 mg

Intervention Type: DRUG

3mL solution for intrathecal injection with 330 mg of AYX1

Interventions

Placebo Injection

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

Intervention Type: DRUG

AYX1 Injection 110 mg

3mL solution for intrathecal injection with 110 mg of AYX1

Intervention Type: DRUG

AYX1 Injection 330 mg

3mL solution for intrathecal injection with 330 mg of AYX1

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Adynxx, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald C Manning, MD, PhD

Role: STUDY_DIRECTOR

Adynxx, Inc.

Locations

Sheffield, Alabama, United States

Phoenix, Arizona, United States

Boynton Beach, Florida, United States

Altoona, Pennsylvania, United States

Houston, Texas, United States

Nassau Bay, Texas, United States

Odessa, Texas, United States

Countries

United States

Other Identifiers

ADYX-002

Identifier Type: -

Identifier Source: org_study_id