Dose Finding Posterolateral Thoracotomy Study

• Sponsor: Pacira Pharmaceuticals, Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00807209
• Collaborator: (none)
• Enrollment: 3
• Locations: 5
• Arms: 3
• Duration (Months): 2
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To review safety and effectiveness of two doses compared to current standard of care.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain	Drug: Low Dose SKY0402; Drug: High Dose SKY0402; Drug: Placebo; Drug: Fentanyl via PCA; Drug: Bupivacaine via epidural	Phase 2

Detailed Description

Evaluate the efficacy of intercostal nerve block using SKY0402 compared to epidural bupivacaine HCl in subjects undergoing posterolateral thoracotomy. The primary outcome metric for this will be the amount of rescue PCA fentanyl administered for breakthrough pain during the first 72 hours.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Open-Label, Parallel Group, Randomized, Dose-Finding Study to Assess the Efficacy and Safety of Intercostal SKY0402 in Subjects Undergoing Posterolateral Thoracotomy
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High Dose SKY0402	Drug: High Dose SKY0402; Bupivacaine, 15 mg/mL via epidural PLUS single total administration of 150 mg (50 mg to each of three segments) in 4 mL volume each for a total of 12 mL via nerve block (intercostal); Drug: Fentanyl via PCA; Fentanyl via PCA; Drug: Bupivacaine via epidural; Bupivacaine via epidural
Active Comparator: Standard of Care	Drug: Placebo; Bupivacaine, 15 mg/mL per epidural PLUS administration of 4 mL Placebo to each of three nerves for a total of 12 mL (intercostal); Drug: Fentanyl via PCA; Fentanyl via PCA; Drug: Bupivacaine via epidural; Bupivacaine via epidural
Experimental: Low Dose SKY0402	Drug: Low Dose SKY0402; Bupivacaine, 15 mg/mL via epidural PLUS single total administration of 75mg SKY0402 (25 mg to each of three segments) in 4 mL volume each for a total of 12 mL via nerve block (intercostal); Drug: Fentanyl via PCA; Fentanyl via PCA; Drug: Bupivacaine via epidural; Bupivacaine via epidural

Outcome Measures

Primary Outcome Measures

1. Amount of Rescue PCA Fentanyl Administered for Breakthrough Pain During the First 72 Hours. [72 hours]

   The primary outcome metric was to be the amount of rescue epidural fentanyl administered for breakthrough pain during the first 72 hours postoperatively. Patient-controlled analgesia (PCA) fentanyl intake was to be summarized for each treatment group as time to first use of rescue PCA fentanyl, amount of PCA fentanyl administered over 72 hours, and total amount of PCA fentanyl administered through a number of time intervals. However, efficacy analyses were not performed because the study was terminated early after only three subjects were enrolled.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Men and women ≥ 18 years of age at the Screening Visit.

• Scheduled to undergo a thoracotomy of at least 3 inches of intercostal incisional length or requiring insertion of an inter-rib spreader/retractor for a primary thoracic non-infectious indication under general anesthesia.

• Able and willing to receive an epidural catheter for the treatment of postoperative pain.

• American Society of Anesthesiology (ASA) Physical Class 1-4.

• Able and willing to comply with all study visits and procedures.

• Able to speak, read, and understand the language of the 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.

• Willing and capable of providing written informed consent.

Exclusion Criteria:

• Known metastatic disease of any type.

• Known pulmonary infectious disease.

• Pregnancy, nursing, or planning to become pregnant during the study or within one month after study drug administration.

• Use of any of the following medications within the times specified before surgery:

1. Long-acting opioids within 3 days.

2. Any opioid medication within 24 hours.

• 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 abdominal surgery, etc.), which have the potential to confound the postoperative study assessments.

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

• History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics, opioid medication, epinephrine, or sulfites.

• Contraindication to epinephrine, such as concurrent administration of ergot-type drugs, monoamine oxidase (MAO) inhibitors or antidepressants of tryptoline 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.

• 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.

• History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.

• Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance with the protocol.

• 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, sever renal impairment, advanced diabetes, co-morbid conditions associated with an immunocompromised status, such as blood dyscrasias, HIV/AIDS, or recent chemotherapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lotus Clinical Research	Pasadena	California	United States	91105
2	Florida Hospital	Orlando	Florida	United States	32801
3	Memorial Hermann - Memorial City Medical Center	Houston	Texas	United States	77024
4	Houston NW Medical Center	Houston	Texas	United States	77053
5	Multicare Health System	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Pacira Pharmaceuticals, Inc

Investigators

• Study Director: Kay Warnott, RN, ACN-P, Pacira Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pacira Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00807209
• Other Study ID Numbers: SKY0402C211
• First Posted: Dec 11, 2008
• Last Update Posted: May 15, 2012
• Last Verified: Nov 1, 2011

• Keywords provided by Pacira Pharmaceuticals, Inc: Pain; postoperative; thoracotomy
• Additional relevant MeSH terms: Pain, Postoperative; Fentanyl; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	High Dose SKY0402	Standard of Care	Low Dose SKY0402
Arm/Group Description
Period Title: Overall Study
STARTED	1	1	1
COMPLETED	1	1	1
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	High Dose SKY0402	Standard of Care	Low Dose SKY0402	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	1	1	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	1 100%	1 33.3%
>=65 years	1 100%	1 100%	0 0%	2 66.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	81 (0)	75 (0)	64 (0)	73.3 (0)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 100%	1 100%	2 66.7%
Male	1 100%	0 0%	0 0%	1 33.3%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Amount of Rescue PCA Fentanyl Administered for Breakthrough Pain During the First 72 Hours.
Description	The primary outcome metric was to be the amount of rescue epidural fentanyl administered for breakthrough pain during the first 72 hours postoperatively. Patient-controlled analgesia (PCA) fentanyl intake was to be summarized for each treatment group as time to first use of rescue PCA fentanyl, amount of PCA fentanyl administered over 72 hours, and total amount of PCA fentanyl administered through a number of time intervals. However, efficacy analyses were not performed because the study was terminated early after only three subjects were enrolled.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Dose SKY0402	Standard of Care	Low Dose SKY0402
Arm/Group Description	Single dose of study drug divided equally into three 4 mL doses and delivered to each of three nerve segments following posterolateral thoracotomy	Bupivacaine HCl solution (1.25 mg/mL) and epinephrine (5 mcg/mL) administered via an epidural catheter at a concentration of 0.125% (1.25 mg/mL) at a rate of 8 cc per hour	Single dose of study drug divided equally into three 4 mL doses and delivered to each of three nerve segments following posterolateral thoracotomy
Measure Participants	0	1	1
Number [micrograms]	0	0

Adverse Events

Arm/Group Title	High Dose SKY0402		Standard of Care		Low Dose SKY0402
Arm/Group Description
All Cause Mortality
	High Dose SKY0402		Standard of Care		Low Dose SKY0402
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	High Dose SKY0402		Standard of Care		Low Dose SKY0402
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	High Dose SKY0402		Standard of Care		Low Dose SKY0402
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		1/1 (100%)
Gastrointestinal disorders
Gas	0/1 (0%)		1/1 (100%)		1/1 (100%)
Diarrhea	0/1 (0%)		1/1 (100%)		0/1 (0%)
Vomiting	1/1 (100%)		0/1 (0%)		0/1 (0%)
Nausea	1/1 (100%)		0/1 (0%)		0/1 (0%)
Injury, poisoning and procedural complications
Swollen Ankle	0/1 (0%)		1/1 (100%)		0/1 (0%)
Pain	1/1 (100%)		0/1 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Difficulty breathing	0/1 (0%)		0/1 (0%)		1/1 (100%)
Blood in nasal mucus	0/1 (0%)		0/1 (0%)		1/1 (100%)

Limitations/Caveats

The study was terminated early due to Sponsor's decision, unrelated to safety. As there was only one patient in each group, no efficacy analyses were performed.

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.