Dose-Ranging Study for Prolonged Postoperative Analgesia in Subject Undergoing Total Knee Arthroplasty (TKA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00485693
First received: June 11, 2007
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

Dose-ranging study for prolonged postoperative analgesia in subjects undergoing total knee arthroplasty


Condition Intervention Phase
Postoperative Pain
Drug: Bupivacaine HCl
Drug: SKY0402
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Multicenter, Randomized, Double-blind, Parallel-group, Active-control, Dose-ranging Study to Evaluate the Safety, Efficacy, and Comparative Systemic Bioavailability of a Single Administration of SKY0402 Via Local Infiltration for Prolonged Postoperative Analgesia in Subjects 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 Through Postoperative Day 4 [ Time Frame: 0 to 96 hours ] [ Designated as safety issue: No ]
    The subject's pain intensity was to be assessed with activity (NRS-A) after actively flexing the involved knee to the maximum flexion point possible. The subject was asked to respond 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 or Serious Adverse Events Through 30 Days [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]

Enrollment: 138
Study Start Date: June 2007
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bupivacaine HCl
Bupivacaine HCl (Marcaine 0.25% with epinephrine 1:200,000)
Drug: Bupivacaine HCl
150 mg Bupivacaine HCl
Other Name: Bupivacaine HCl (Marcaine 0.25% with epinephrine 1:200,000)
SKY0402
SKY0402 at various dosage levels. Single administration.
Drug: SKY0402
600 mg SKY0402 (study drug)
Other Name: EXPAREL

Detailed Description:

This is a phase 2, multicenter, parallel-group, active-control, randomized, double-blind, dose-ranging study conducted to evaluate three dose levels of SKY0402 compared with 150 mg of bupivacaine HCl.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, greater than or equal to 18 and less than or equal to 75 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 total knee arthroplasty (TKA) under general anesthesia.
  4. American Society of Anesthesiology (ASA) Physical Class 1-3.
  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, 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 administered study treatment, and which may confound the postoperative assessments (e.g., significant pain from other joints, chronic neuropathic pain, concurrent contralateral TKA, concurrent foot surgery, etc.).
  4. Body weight less than 50 kilograms (110 pounds) or morbid obesity.
  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 monoamine oxidase (MAO) inhibitors or antidepressants of amitriptyline 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. History of, 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, especially cardiovascular or neurological conditions 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 criteria 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: NCT00485693

Locations
United States, Alabama
West Alabama Research
Birmingham, Alabama, United States, 35209
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: NCT00485693     History of Changes
Other Study ID Numbers: SKY0402C208
Study First Received: June 11, 2007
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:
pain
postoperative
total knee arthroplasty
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 September 30, 2014