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

• Sponsor: Pacira Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00529126
• Collaborator: (none)
• Enrollment: 100
• Locations: 7
• Arms: 4
• Duration (Months): 10
• Patients Per Site: 14.3
• Patients Per Site Per Month: 1.4

Study Details

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
• 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: Sep 1, 2007
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SKY0402 high dose SKY0402, single administration	Drug: SKY0402; SKY0402; Other Names: EXPAREL
Experimental: SKY0402 middle dose SKY0402, single administration	Drug: SKY0402; SKY0402; Other Names: EXPAREL
Experimental: SKY0402 low dose SKY0402, single administration	Drug: SKY0402; SKY0402; Other Names: EXPAREL
Active Comparator: Bupivacaine HCl Bupivacaine HCl	Drug: Bupivacaine HCl; Bupivacaine HCl; Other Names: 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 [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 [Up to 30 days]

Eligibility Criteria

Criteria

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

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.

1. 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).

2. Single-column hemorrhoidectomy or hemorrhoidectomy without an internal component.

3. Body weight less than 50 kilograms (110 pounds).

4. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or to opioid medication.

5. 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.

6. Contraindications to any of the pain-control agents planned for postoperative use (e.g., acetaminophen [paracetamol], oxycodone, morphine, ketorolac).

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. 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:

1. 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.

2. A cumulative incision length less than 3 cm.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Accurate Clinical Trials, Inc.	San Clemente	California	United States	92673
2	University of Miami/Jackson Memorial	Miami	Florida	United States	33136
3	The Women's Hospital of Texas	Houston	Texas	United States	77054
4	Multicare Health Systems Laboratories	Tacoma	Washington	United States	98405
5	JSC Imereti Regional Clinical Hospital of the Name A. Dzotsenidze	Kutaisi		Georgia	4600
6	JSC K. Eristavi National Center of Experimental and Clinical Surgery	Tbilisi		Georgia	0159
7	Socieety with limited responsibility Proctology Center	Tbilisi		Georgia	0160

Sponsors and Collaborators

• Pacira Pharmaceuticals, Inc

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pacira Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00529126
• Other Study ID Numbers: SKY0402C209
• First Posted: Sep 14, 2007
• Last Update Posted: Mar 4, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Pacira Pharmaceuticals, Inc: hemorrhoidectomy; pain; Postoperative; analgesia
• Additional relevant MeSH terms: Pain, Postoperative; Epinephrine; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	SKY0402 High Dose (300mg)	SKY0402 Middle Dose (225mg)	SKY0402 Low Dose (75mg)	Bupivacaine HCl 75mg
Arm/Group Description	SKY0402 300mg single dose administered intraoperatively via local infiltration.	A single dose 225mg SKY0402 administered intraoperatively via local infiltration.	A single dose 75mg SKY0402 administered intraoperatively via local infiltration.	A single dose of 75 mg bupivacaine administered intraoperatively via local infiltration
Period Title: Overall Study
STARTED	25	25	24	26
COMPLETED	25	25	24	26
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	SKY0402 High Dose	SKY0402 Middle Dose	SKY0402 Low Dose	Bupivacaine HCl	Total
Arm/Group Description	A single dose of study drug was to be administered intraoperatively via local infiltration.	A single dose of study drug was to be administered intraoperatively via local infiltration.	A single dose of study drug was to be administered intraoperatively via local infiltration.	A single dose of 75 mg bupivacaine was to be administered intraoperatively via local infiltration	Total of all reporting groups
Overall Participants	25	25	24	26	100
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	23 92%	24 96%	23 95.8%	25 96.2%	95 95%
>=65 years	2 8%	1 4%	1 4.2%	1 3.8%	5 5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (11.3)	41.7 (11.2)	42.2 (11.5)	44.2 (10.6)	43.4 (11.1)
Sex: Female, Male (Count of Participants)
Female	3 12%	9 36%	7 29.2%	11 42.3%	30 30%
Male	22 88%	16 64%	17 70.8%	15 57.7%	70 70%
Region of Enrollment (participants) [Number]
United States	5 20%	9 36%	9 37.5%	14 53.8%	37 37%
Georgia	20 80%	16 64%	15 62.5%	12 46.2%	63 63%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) at Rest (NRS-R) Pain Intensity Scores From 0 Through 72 Hours
Description	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?"
Time Frame	0 to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SKY0402 300mg	SKY0402 225mg	SKY0402 75mg	Bupivacaine HCl
Arm/Group Description	A single dose of SKY0402 300mg administered intraoperatively via local infiltration.	A single dose of SKY0402 225mg administered intraoperatively via local infiltration.	A single dose of SKY0402 75mg administered intraoperatively via local infiltration.	A single dose of 75 mg bupivacaine was to be administered intraoperatively via local infiltration
Measure Participants	25	25	24	26
Mean (Standard Deviation) [units on a scale*hrs]	175 (173)	172 (146)	225 (185)	331 (175)

2. Secondary Outcome

Title	Participants With Adverse Events Through 72 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	SKY0402 High Dose		SKY0402 Middle Dose		SKY0402 Low Dose		Bupivacaine HCl
Arm/Group Description	A single dose of study drug was to be administered intraoperatively via local infiltration.		A single dose of study drug was to be administered intraoperatively via local infiltration.		A single dose of study drug was to be administered intraoperatively via local infiltration.		A single dose of 75 mg bupivacaine was to be administered intraoperatively via local infiltration
All Cause Mortality
	SKY0402 High Dose		SKY0402 Middle Dose		SKY0402 Low Dose		Bupivacaine HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SKY0402 High Dose		SKY0402 Middle Dose		SKY0402 Low Dose		Bupivacaine HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)		1/24 (4.2%)		0/26 (0%)
Vascular disorders
Rectal hemorrhage	0/25 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0
Other (Not Including Serious) Adverse Events
	SKY0402 High Dose		SKY0402 Middle Dose		SKY0402 Low Dose		Bupivacaine HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		7/25 (28%)		7/24 (29.2%)		10/26 (38.5%)
Gastrointestinal disorders
Constipation	0/25 (0%)	0	5/25 (20%)	0	3/24 (12.5%)	0	4/26 (15.4%)	0
Nausea	0/25 (0%)	0	4/25 (16%)	0	3/24 (12.5%)	0	3/26 (11.5%)	0
Vomiting	0/25 (0%)	0	3/25 (12%)	0	1/24 (4.2%)	0	3/26 (11.5%)	0

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.