Clinical trial NCT00745290: A Phase 3 Study to Evaluate the Safety and Efficacy of SKY0402 in Subjects Undergoing Total Knee Arthroplasty
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Pain
Keywords: Total knee arthroplasty
Pain
Analgesia
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2008-09-03
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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 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.

Primary outcomes:
measure: Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores
timeFrame: through 72 hours post surgery
Secondary outcomes:
measure: Number of Participants With Adverse Events Through 96 Hours and Serious Adverse Events Through 30 Days
timeFrame: through 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: West Alabama Research, Inc.
state: Alabama
city: Mobile
country: United States
facility: Horizon Research Group, Inc., Alabama Orthopaedic Clinic
state: Alabama
city: Montgomery
country: United States
facility: Drug Research and Analysis Corporation
state: Alabama
city: Sun City West
country: United States
facility: Sun Health Research Institute, Core Institute
state: Arizona
city: La Jolla
country: United States
facility: Scripps
state: California
city: Laguna Hills
country: United States
facility: Accurate Clinical Trials, Inc.
state: California
city: Laguna Hills
country: United States
facility: Physicans Clinical Research Corp.
state: California
city: Los Angeles
country: United States
facility: Cedars of Sinai Medical Center
state: California
city: Decatur
country: United States
facility: Atlanta Knee and Sports Medicine
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New York
country: United States
facility: Insall Scott Kelly Institute
state: New York
city: Greenville
country: United States
facility: CTMG, Inc.
state: North Carolina
city: Raleigh-Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Altoona
country: United States
facility: Allegheny Pain Management
state: Pennsylvania
city: Johnstown
country: United States
facility: Ilumina Clinical Associates
state: Pennsylvania
city: Jackson
country: United States
facility: Research Associates of Jackson
state: Tennessee
city: Grapevine
country: United States
facility: Texas Orthopedic Specialists, PA
state: Texas
city: Houston
country: United States
facility: Memorial Hermann City Hospital
state: Texas
Study officials:
affiliation: Pacira Pharmaceuticals, Inc
name: Joyce Davis, RN
role: STUDY_DIRECTOR
References:
citation: Dasta J, Ramamoorthy S, Patou G, Sinatra R. Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. Curr Med Res Opin. 2012 Oct;28(10):1609-15. doi: 10.1185/03007995.2012.721760. Epub 2012 Sep 3.