A Pharmacokinetic (PK) Study of Extended-Release Epidural Morphine in Upper Abdominal Surgery

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the effects of lidocaine/epinephrine test dose administration on the PK profile of a single epidural dose of DepoDur (extended-release epidural morphine) in patients undergoing major upper abdominal surgery. A secondary objective was to evaluate the safety and efficacy profile.

Official Title
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A Phase 1 Study to Evaluate the Effects of Lidocaine/Epinephrine Test Dose Administration on the Pharmacokinetic Profile of a Single Dose of Thoracic Extended-Release Epidural Morphine in Patients Undergoing Major Upper Abdominal Surgery

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: DepoDur (extended-release epidural morphine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age at Screening Negative pregnancy test in females of childbearing potential Scheduled for major upper abdominal surgery via an upper midline incision under general anesthesia American Society of Anesthesiology (ASA) Physical Class 1, 2, or 3 Willing and able to use a PCA pump Willing to receive only IV fentanyl for 72 hours post-dose to control post-operative pain Capable of providing written informed consent and responses to pain assessment scales and neurological assessment questionnaires Exclusion Criteria: Morbid obesity, defined as a body mass index (BMI) ≥ 40 Scheduled to undergo surgery under regional anesthesia Usage of analgesic medications containing morphine or codeine within three days prior to study drug administration Chronic opioid medication usage (defined as daily opioids for more than 7 days prior to enrollment) Suspected or documented history of sleep apnea, narcolepsy, or excessive daytime sleepiness Female who was pregnant or lactating History of hypersensitivity or idiosyncratic reaction to opioid medications, local anesthetics, or epinephrine Any contraindication for the epidural administration of study drug (e.g., coagulopathy, local infection) Administration of an investigational drug within 30 days prior to Screening Suspected or documented history of substance abuse and/or alcoholism Any contraindication to frequent blood PK sampling (such as significant anemia) or other barrier to obtaining timely PK samples

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>No test dose + DepoDur + flush with 1 mL normal saline | Drug: DepoDur (extended-release epidural morphine)<br>* DepoDur with on demand boluses of IV fentanyl PCA<br>|
| Experimental: 2<br>Test dose + flush with 1 mL normal saline + 3-minute wait + DepoDur + flush with 1 mL normal saline | Drug: DepoDur (extended-release epidural morphine)<br>* DepoDur with on demand boluses of IV fentanyl PCA<br>|
| Experimental: 3<br>Test dose + flush with 1 mL normal saline + 10-minute wait + DepoDur + flush with 1 mL normal saline | Drug: DepoDur (extended-release epidural morphine)<br>* DepoDur with on demand boluses of IV fentanyl PCA<br>|
| Experimental: 4<br>Test dose + flush with 1 mL normal saline + 15-minute wait + DepoDur + flush with 1 mL normal saline | Drug: DepoDur (extended-release epidural morphine)<br>* DepoDur with on demand boluses of IV fentanyl PCA<br>|
| Experimental: 5<br>Test dose + No flush + 3-minute wait + DepoDur + flush with 1 mL normal saline | Drug: DepoDur (extended-release epidural morphine)<br>* DepoDur with on demand boluses of IV fentanyl PCA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the serum pharmacokinetic profile of a single 15-mg dose of DepoDur administered at the lower thoracic epidural space with or without a prior lidocaine-epinephrine test dose |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy and safety profiles |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extended release epidural morphine, morphine, thoracic epidural, pharmacokinetics, pharmacodynamics, postoperative pain, upper abdominal surgery