A Phase 3 Study to Evaluate the Safety and Efficacy of SKY0402 in Subjects Undergoing Total Knee Arthroplasty (TKA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00745290
First received: August 29, 2008
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

The primary objective is to demonstrate that SKY0402 is superior when compared to bupivacaine HCl in the management of postoperative pain for patients undergoing total knee arthroplasty.


Condition Intervention Phase
Postoperative Pain
Drug: Bupivacaine HCl
Drug: SKY0402
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Active Control Study to Evaluate the Safety and Efficacy of a Single Intraoperative Administration of SKY0402 For Prolonged Postoperative Analgesia in Subject Undergoing Total Knee Arthroplasty

Resource links provided by NLM:


Further study details as provided by Pacira Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores [ Time Frame: through 72 hours post surgery ] [ Designated as safety issue: Yes ]
    The subject's pain intensity was assessed with activity (NRS-A), while actively flexing the involved knee from the maximum extension point to the maximum flexion point possible. The subject responded to the following question, "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain did you have while bending your knee?"


Secondary Outcome Measures:
  • Number of Participants With Adverse Events Through 96 Hours and Serious Adverse Events Through 30 Days [ Time Frame: through 30 days ] [ Designated as safety issue: Yes ]

Enrollment: 245
Study Start Date: August 2008
Study Completion Date: February 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bupivacaine HCl
Single dose of 200 mg bupivacaine HCl administered intraoperatively via local infiltration
Drug: Bupivacaine HCl
200 mg bupivacaine HCl
Other Name: Marcaine
SKY0402
Single dose of 600 mg SKY0402 (study drug) administered intraoperatively via local infiltration
Drug: SKY0402
600 mg SKY0402 (study drug).
Other Name: DepoBupivacaine

Detailed Description:

The primary objective is to demonstrate the superiority of SKY0402, compared with bupivacaine HC1, with respect to the extent and duration of the analgesic effect achieved by a single intraoperative administration of the study drug via local infiltration in subjects undergoing total knee arthroplasty (TKA).

The secondary objectives are to evaluate additional efficacy parameters and characterize the safety profile of SKY0402 in comparison with bupivacaine HCl.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, ≥18 years of age at the Screening Visit.
  2. Female subjects only: Postmenopausal, surgically sterile, or willing to use acceptable means of contraception for at least 30 days after surgery including any of the following: hormonal contraceptives (e.g., oral, injectable, implantable starting at least 30 days before study drug administration), effective double-barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, nonheterosexual lifestyle, or a strictly monogamous relationship with a partner who has had a vasectomy.
  3. Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.
  4. American Society of Anesthesiology (ASA) Physical Classification System class 1-4.
  5. Able and willing to comply with all study visits and procedures.
  6. Able to speak, read, and understand the language of the informed consent form, study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments.
  7. Willing and capable of providing written informed consent.

Exclusion Criteria:

  1. Pregnancy, nursing, or planning to become pregnant during the study or within one month after dosing.
  2. Use of any of the following medications within the times specified before surgery:

    • Long-acting opioid medication within 3 days.
    • Any opioid medication within 24 hours.
  3. Concurrent painful physical condition or concurrent surgery that may require analgesic treatment in the postoperative period for pain that is not strictly related to the surgical site being administered study drug (e.g., significant pain from other joints, chronic neuropathic pain, concurrent contralateral TKA, concurrent foot surgery, etc.), which have the potential to confound the postoperative study assessments.
  4. Body weight less than 60 kilograms (~132 pounds).
  5. Contraindication to any of the pain-control agents planned for postoperative use (e.g., acetaminophen, morphine, oxycodone, ketorolac).
  6. Contraindication to epinephrine, such as concurrent administration of ergot-type drugs, monoamine oxidase (MAO) inhibitors or antidepressants of triptoline or imipramine types, conditions where the production or exacerbation of tachycardia could prove fatal (e.g., poorly controlled thyrotoxicosis or severe heart disease), or any other pathological conditions that might be aggravated by the effects of epinephrine.
  7. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.
  8. Suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
  9. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance.
  10. Current or historical evidence of any clinically significant disease or condition that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postoperative course.
  11. Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures, and expose the subject to an unreasonable risk as a result of participating in this clinical trial, such as: debilitating diseases, acute illnesses, hypotension, partial or complete conduction block, impaired cardiac function, untreated hypertension, advanced arteriosclerotic heart disease, cerebral vascular insufficiency, pre-existing abnormal neurological or neuromuscular disease (e.g., epilepsy, myasthenia gravis), advanced liver disease, severe renal impairment, advanced diabetes, comorbid conditions associated with an immunocompromised status, such as blood dyscrasias, HIV/AIDS, or recent chemotherapy.

    In addition, the subject will be ineligible to receive study drug if he or she meets the following criterion during surgery:

  12. Any clinically significant event or condition uncovered during surgery (e.g., excessive bleeding), which occurs before study drug administration, that might render the subject medically unstable or complicate the subject's postoperative course.
  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: NCT00745290

Locations
United States, Alabama
West Alabama Research, Inc.
Birmingham, Alabama, United States, 35209
Horizon Research Group, Inc., Alabama Orthopaedic Clinic
Mobile, Alabama, United States, 36608
Drug Research and Analysis Corporation
Montgomery, Alabama, United States, 36106
United States, Arizona
Sun Health Research Institute, Core Institute
Sun City West, Arizona, United States, 85375
United States, California
Scripps
La Jolla, California, United States, 92037
Accurate Clinical Trials, Inc.
Laguna Hills, California, United States, 92653
Physicans Clinical Research Corp.
Laguna Hills, California, United States, 92653
Cedars of Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Georgia
Atlanta Knee and Sports Medicine
Decatur, Georgia, United States, 30033
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, New York
Insall Scott Kelly Institute
New York, New York, United States, 10065
United States, North Carolina
CTMG, Inc.
Greenville, North Carolina, United States, 27834
Duke University Medical Center
Raleigh-Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Allegheny Pain Management
Altoona, Pennsylvania, United States, 16602
Ilumina Clinical Associates
Johnstown, Pennsylvania, United States, 15904
United States, Tennessee
Research Associates of Jackson
Jackson, Tennessee, United States, 38301
United States, Texas
Texas Orthopedic Specialists, PA
Grapevine, Texas, United States, 76051
Memorial Hermann City Hospital
Houston, Texas, United States, 77024
Sponsors and Collaborators
Pacira Pharmaceuticals, Inc
Investigators
Study Director: Joyce Davis, RN Pacira Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00745290     History of Changes
Other Study ID Numbers: SIMPLE TKA 311
Study First Received: August 29, 2008
Results First Received: November 23, 2011
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pacira Pharmaceuticals, Inc:
Total knee arthroplasty
Pain
Analgesia

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Bupivacaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014