Phase 2 Dose-Ranging Study of SKY0402 for Prolonged Postoperative Analgesia in Subject Undergoing Hemorrhoidectomy

• ClinicalTrials.gov Identifier: NCT00529126
• Recruitment Status: Completed
• First Posted: September 14, 2007
• Results First Posted: August 6, 2013
• Last Update Posted: March 4, 2021
• Sponsor: Pacira Pharmaceuticals, Inc
• Information provided by (Responsible Party): Pacira Pharmaceuticals, Inc

Study Description

Brief Summary:

Phase 2 study to evaluate three dose levels of SKY0402 compared with 75 mg of bupivacaine HCl.

Condition or disease	Intervention/treatment	Phase
Postoperative Pain	Drug: SKY0402; Drug: Bupivacaine HCl	Phase 2

Detailed Description:

Effective postoperative pain control is a critical element in patient recovery, as the majority of patients may experience significant pain, particularly in the first few days following surgery. Appropriate postoperative pain management contributes to improved healing, faster patient mobilization, shortened hospital stays, and reduced healthcare costs.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter, Randomized, Double-blind, Parallel-group, Active-control, Dose-ranging Study to Evaluate the Safety and Efficacy of a Single Administration of SKY0402 for Prolonged Postoperative Analgesia in Subject Undergoing Hemorrhoidectomy
• Study Start Date: September 2007
• Actual Primary Completion Date: December 2007
• Actual Study Completion Date: July 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: SKY0402 high dose; SKY0402, single administration	Drug: SKY0402; SKY0402; Other Name: EXPAREL
Experimental: SKY0402 middle dose; SKY0402, single administration	Drug: SKY0402; SKY0402; Other Name: EXPAREL
Experimental: SKY0402 low dose; SKY0402, single administration	Drug: SKY0402; SKY0402; Other Name: EXPAREL
Active Comparator: Bupivacaine HCl; Bupivacaine HCl	Drug: Bupivacaine HCl; Bupivacaine HCl; Other Name: Marcaine 0.25% with epinephrine 1:200,000

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) at Rest (NRS-R) Pain Intensity Scores From 0 Through 72 Hours [ Time Frame: 0 to 72 hours ]
   To assess pain intensity at rest (NRS-R), the subject was to assume a resting position that did not exacerbate his or her postoperative pain. The subject was to rest in this position for at least 5 minutes before responding to the following question: "On a scale of 0 to 10, where 0=no pain and 10=worst possible pain, how much pain are you having right now?"

Secondary Outcome Measures :

1. Participants With Adverse Events Through 72 Hours or Serious Adverse Events Through 30 Days [ Time Frame: Up to 30 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female, 18 years of age and older at the Screening Visit.
2. Applies to 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 2- or 3-column excisional hemorrhoidectomy under general anesthesia using Milligan Morgan or Ferguson-type techniques, including modified approaches with specialized instruments, such as LigaSure™ or harmonic scalpel, with a cumulative incision length of a minimum 3 cm.
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 Form (ICF), 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 study drug administration.

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 that may require analgesic treatment in the postoperative period for pain that is not surgically related and may confound the postoperative assessments (e.g., rheumatoid arthritis, chronic neuropathic pain).
4. Single-column hemorrhoidectomy or hemorrhoidectomy without an internal component.
5. Body weight less than 50 kilograms (110 pounds).
6. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or to opioid medication.
7. 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.
8. Contraindications to any of the pain-control agents planned for postoperative use (e.g., acetaminophen [paracetamol], oxycodone, morphine, ketorolac).
9. 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.
10. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
11. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance.

12. 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:

13. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postoperative course.
14. A cumulative incision length less than 3 cm.

Contacts and Locations

Locations

United States, California

Accurate Clinical Trials, Inc.

San Clemente, California, United States, 92673

United States, Florida

University of Miami/Jackson Memorial

Miami, Florida, United States, 33136

United States, Texas

The Women's Hospital of Texas

Houston, Texas, United States, 77054

United States, Washington

Multicare Health Systems Laboratories

Tacoma, Washington, United States, 98405

Georgia

JSC Imereti Regional Clinical Hospital of the Name A. Dzotsenidze

Kutaisi, Georgia, 4600

JSC K. Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, Georgia, 0159

Socieety with limited responsibility Proctology Center

Tbilisi, Georgia, 0160

Sponsors and Collaborators

Pacira Pharmaceuticals, Inc

Investigators

• Study Director: Erol Onel, MD; Pacira Pharmaceuticals, Inc

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pacira Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00529126
• Other Study ID Numbers: SKY0402C209
• First Posted: September 14, 2007
• Results First Posted: August 6, 2013
• Last Update Posted: March 4, 2021
• Last Verified: February 2021

Keywords provided by Pacira Pharmaceuticals, Inc:

hemorrhoidectomy; pain; Postoperative; analgesia

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Epinephrine; Bupivacaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-Agonists; Bronchodilator Agents; Autonomic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Sympathomimetics; Vasoconstrictor Agents