Dose Finding Posterolateral Thoracotomy Study

Study Overview
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Brief Summary
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To review safety and effectiveness of two doses compared to current standard of care.

Detailed Description
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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.

Official Title
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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

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Low Dose SKY0402
* Drug: High Dose SKY0402
* Drug: Placebo
* Drug: Fentanyl via PCA
* Drug: Bupivacaine via epidural


Participation Criteria
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Eligibility Criteria
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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: Long-acting opioids within 3 days. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose SKY0402<br> | Drug: High Dose SKY0402<br>* 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)<br>Drug: Fentanyl via PCA<br>* Fentanyl via PCA<br>Drug: Bupivacaine via epidural<br>* Bupivacaine via epidural<br>|
| Active Comparator: Standard of Care<br> | Drug: Placebo<br>* Bupivacaine, 15 mg/mL per epidural PLUS administration of 4 mL Placebo to each of three nerves for a total of 12 mL (intercostal)<br>Drug: Fentanyl via PCA<br>* Fentanyl via PCA<br>Drug: Bupivacaine via epidural<br>* Bupivacaine via epidural<br>|
| Experimental: Low Dose SKY0402<br> | Drug: Low Dose SKY0402<br>* 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)<br>Drug: Fentanyl via PCA<br>* Fentanyl via PCA<br>Drug: Bupivacaine via epidural<br>* Bupivacaine via epidural<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Rescue PCA Fentanyl Administered for Breakthrough Pain During the First 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. | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, postoperative, thoracotomy