Dose-ranging Study for Postoperative Analgesia in Subjects Undergoing Primary Unilateral Inguinal Hernia Repair

• Sponsor: Pacira Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00485433
• Collaborator: (none)
• Enrollment: 98
• Locations: 7
• Arms: 4
• Duration (Months): 14
• Patients Per Site: 14
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate three dose levels of SKY0402 compared with 105 mg of bupivacaine HCl.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain	Drug: Bupivacaine HCl; Drug: SKY0402	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
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• 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 Subjects Undergoing Primary Unilateral Inguinal Hernia Repair.
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bupivacaine HCl 105mg Bupivacaine HCl given during hernia repair	Drug: Bupivacaine HCl; Bupivacaine HCl given during hernia repair; Other Names: Marcaine 0.25% with epinephrine 1:200,000
Experimental: SKY0402 low dose SKY0402 low dose given during hernia repair	Drug: SKY0402; SKY0402 given during hernia repair; Other Names: EXPAREL
Experimental: SKY0402 Middle dose SKY0402 middle dose given during hernia repair	Drug: SKY0402; SKY0402 given during hernia repair; Other Names: EXPAREL
Experimental: SKY0402 High dose SKY0402 high dose given during hernia repair	Drug: SKY0402; SKY0402 given during hernia repair; Other Names: EXPAREL

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores From 0 Through 72 Hours [0 to 72 hours]

   The subject's pain intensity was to be assessed with activity (NRS-A), after the subject had moved himself from a supine position in bed to a sitting up position at the edge of the bed. The subject was 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 sitting up?"

Secondary Outcome Measures

1. Number of Participants With Adverse Events Through 96 Hours or Serious Adverse Events Through 30 Days [Up to 30 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males 18 years of age and older at the Screening Visit.

2. Scheduled to undergo, elective, primary, unilateral, open-technique, tension-free (Lichtenstein-type technique with mesh) inguinal hernia repair under general anesthesia.

3. American Society of Anesthesiology (ASA) Physical Class 1-3.

4. Capable and willing to comply with all study visits and procedures and to provide written informed consent.

5. 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.

Exclusion Criteria:

1. 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.

1. Concurrent painful physical condition that may require analgesic treatment in the postoperative period for pain that is not strictly related to the hernia repair procedure and may confound the postoperative assessments (e.g., rheumatoid arthritis, neuropathic pain, concomitant vasectomy).

2. Body weight less than 50 kilograms.

3. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.

4. Other contraindication to bupivacaine.

5. Contraindication(s) 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.

6. Contraindication to any of the pain control agents anticipated to be used postoperatively (i.e., acetaminophen or oxycodone).

7. Administration of an investigational product within 30 days or 5 elimination half-lives of such investigational product, 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 condition that, in the opinion of the Investigator, may increase the risk of surgery, complicate the subject's postoperative course, or 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.

If during surgery the following criterion is met:

1. Any clinically significant event or condition uncovered during the hernia repair surgery (e.g., excessive bleeding) that might render the subject medically unstable or complicate the subject's postoperative course.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arcadia Methodist Hospital	Arcadia	California	United States	91007
2	Saddleback Valley Outpatient Surgery	Laguna Hills	California	United States	92653
3	Huntington Memorial Hospital	Pasadena	California	United States	91105
4	St. Luke's Roosevelt Hosptial Center	New York	New York	United States	10025
5	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
6	Memorial Hermann Healthcare System	Houston	Texas	United States	77024
7	Kirby Outpatient Surgical Center	Houston	Texas	United States	77054

Sponsors and Collaborators

• Pacira Pharmaceuticals, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pacira Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00485433
• Other Study ID Numbers: SKY0402-C-207
• First Posted: Jun 13, 2007
• Last Update Posted: Mar 2, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Pacira Pharmaceuticals, Inc: hernia; unilateral; postoperative; analgesia
• Additional relevant MeSH terms: Hernia; Hernia, Inguinal; Epinephrine; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Bupivacaine HCl 105mg	SKY0402 Low Dose	SKY0402 Middle Dose	SKY0402 High Dose
Arm/Group Description	Bupivacaine HCl given during hernia repair	SKY0402 low dose given during hernia repair	SKY0402 middle dose given during hernia repair	SKY0402 high dose given during hernia repair
Period Title: Overall Study
STARTED	24	25	24	25
COMPLETED	24	25	24	25
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Bupivacaine HCl 105mg	SKY0402 Low Dose	SKY0402 Middle Dose	SKY0402 High Dose	Total
Arm/Group Description	Bupivacaine HCl given during hernia repair	SKY0402 low dose given during hernia repair	SKY0402 middle dose given during hernia repair	SKY0402 high dose given during hernia repair	Total of all reporting groups
Overall Participants	24	25	24	25	98
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	21 87.5%	19 76%	18 75%	21 84%	79 80.6%
>=65 years	3 12.5%	6 24%	6 25%	4 16%	19 19.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (16.9)	51.2 (17.3)	54 (15.1)	52.1 (15.6)	51.1 (16.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	24 100%	25 100%	24 100%	25 100%	98 100%
Region of Enrollment (participants) [Number]
United States	24 100%	25 100%	24 100%	25 100%	98 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores From 0 Through 72 Hours
Description	The subject's pain intensity was to be assessed with activity (NRS-A), after the subject had moved himself from a supine position in bed to a sitting up position at the edge of the bed. The subject was 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 sitting up?"
Time Frame	0 to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine HCl 105mg	SKY0402 Low Dose	SKY0402 Middle Dose	SKY0402 High Dose
Arm/Group Description	A single dose of 105 mg bupivacaine in a 42-mL injection volume administered via local infiltration during surgery	A single dose of SKY0402 105mg diluted to a 42-mL injection volume administered via local infiltration during surgery	A single dose of SKY0402 180mg diluted to a 42-mL injection volume administered via local infiltration during surgery	A single dose of SKY0402 345 mg diluted to a 42-mL injection volume administered via local infiltration during surgery
Measure Participants	24	25	24	25
Mean (Standard Deviation) [Units on a scale*hours]	298.1 (136.6)	286.9 (146.4)	274.6 (115.4)	274.4 (253.4)

2. Secondary Outcome

Title	Number of Participants With Adverse Events Through 96 Hours or Serious Adverse Events Through 30 Days
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Bupivacaine HCl 105mg		SKY0402 (All Doses)
Arm/Group Description	Bupivacaine HCl given during hernia repair		SKY0402 given during hernia repair
All Cause Mortality
	Bupivacaine HCl 105mg		SKY0402 (All Doses)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bupivacaine HCl 105mg		SKY0402 (All Doses)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		1/74 (1.4%)
Injury, poisoning and procedural complications
Scar	0/24 (0%)	0	1/74 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Bupivacaine HCl 105mg		SKY0402 (All Doses)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/24 (41.7%)		17/74 (23%)
Cardiac disorders
Bradycardia	0/24 (0%)	0	4/74 (5.4%)	0
Gastrointestinal disorders
Nausea	5/24 (20.8%)		6/74 (8.1%)
Constipation	2/24 (8.3%)		7/74 (9.5%)
Nervous system disorders
Dizziness	2/24 (8.3%)		6/74 (8.1%)
Hypoaesthesia	2/24 (8.3%)		1/74 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.