Clinical trial NCT00485693: Dose-Ranging Study for Prolonged Postoperative Analgesia in Subject Undergoing Total Knee Arthroplasty
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Pain
Keywords: pain
postoperative
total knee arthroplasty
analgesia
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2007-06-13
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores Through Postoperative Day 4
timeFrame: 0 to 96 hours
Secondary outcomes:
measure: Number of Participants With Adverse Events or Serious Adverse Events Through 30 Days
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: West Alabama Research, Inc.
state: Alabama
city: Davis
country: United States
facility: California Clinical Research, Inc.
state: California
city: Laguna Hills
country: United States
facility: Accurate Clinical Trials, Inc.
state: California
city: New York
country: United States
facility: St. Luke's Roosevelt Hospital
state: New York
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: Brno
country: Czechia
facility: Urazova Nemocnice Brno
city: Kladno
country: Czechia
facility: Regional Hospital Kladno
city: Třebíč
country: Czechia
facility: The Hospital Trebic
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.