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

NCT ID: NCT02081703

Last Updated: 2015-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2015-06-30

Brief Summary

The objectives of this study are to evaluate the safety and analgesic efficacy of a single preoperative intrathecal administration of AYX1 Injection at two dose/volume levels.

Conditions

Postsurgical Pain

Study Design

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

Study Groups

AYX1 Injection 660 mg / 6 mL

Single Intrathecal (spinal) administration of AYX1 Injection (660 mg in 6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery

Group Type: EXPERIMENTAL

AYX1 Injection 660 mg / 6 mL

Intervention Type: DRUG

6 mL solution for intrathecal injection with 660 mg of AYX1

Placebo Injection 6 mL

Single Intrathecal (spinal) administration of Placebo Injection (6 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery

Group Type: PLACEBO_COMPARATOR

Placebo Injection 6 mL

Intervention Type: DRUG

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

AYX1 Injection 1100 mg / 10 mL

Single Intrathecal (spinal) administration of AYX1 Injection (1100 mg in 10 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery

Group Type: EXPERIMENTAL

AYX1 Injection 1100 mg / 10 mL

Intervention Type: DRUG

10 mL solution for intrathecal injection with 1100 mg of AYX1

Placebo Injection 10 mL

Single Intrathecal (spinal) administration of Placebo Injection (10 mL) just prior to intrathecal administration of spinal anesthetic for knee surgery

Group Type: PLACEBO_COMPARATOR

Placebo Injection 10 mL

Intervention Type: DRUG

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

Interventions

AYX1 Injection 660 mg / 6 mL

6 mL solution for intrathecal injection with 660 mg of AYX1

Intervention Type: DRUG

AYX1 Injection 1100 mg / 10 mL

10 mL solution for intrathecal injection with 1100 mg of AYX1

Intervention Type: DRUG

Placebo Injection 6 mL

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

Intervention Type: DRUG

Placebo Injection 10 mL

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

Intervention Type: DRUG

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

• 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

Countries

United States

Other Identifiers

ADYX-003

Identifier Type: -

Identifier Source: org_study_id