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

Postoperative Pain Clinical Trial

— TKA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00745290
• Other study ID #: SIMPLE TKA 311
• Status: Completed
• Phase: Phase 3
• First received: August 29, 2008
• Last updated: July 3, 2013
• Start date: August 2008
• Est. completion date: February 2009

Study information

• Verified date: July 2013
• Source: Pacira Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 245
• Est. completion date: February 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Bupivacaine HCl
200 mg bupivacaine HCl
• SKY0402
600 mg SKY0402 (study drug).

Locations

Country	Name	City	State
United States	Allegheny Pain Management	Altoona	Pennsylvania
United States	West Alabama Research, Inc.	Birmingham	Alabama
United States	Rush University Medical Center	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Atlanta Knee and Sports Medicine	Decatur	Georgia
United States	Texas Orthopedic Specialists, PA	Grapevine	Texas
United States	CTMG, Inc.	Greenville	North Carolina
United States	Memorial Hermann City Hospital	Houston	Texas
United States	Research Associates of Jackson	Jackson	Tennessee
United States	Ilumina Clinical Associates	Johnstown	Pennsylvania
United States	Scripps	La Jolla	California
United States	Accurate Clinical Trials, Inc.	Laguna Hills	California
United States	Physicans Clinical Research Corp.	Laguna Hills	California
United States	Cedars of Sinai Medical Center	Los Angeles	California
United States	Horizon Research Group, Inc., Alabama Orthopaedic Clinic	Mobile	Alabama
United States	Drug Research and Analysis Corporation	Montgomery	Alabama
United States	Insall Scott Kelly Institute	New York	New York
United States	Duke University Medical Center	Raleigh-Durham	North Carolina
United States	Sun Health Research Institute, Core Institute	Sun City West	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pacira Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores	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?"	through 72 hours post surgery	Yes
Secondary	Number of Participants With Adverse Events Through 96 Hours and Serious Adverse Events Through 30 Days		through 30 days	Yes