An International Trial to Evaluate the Efficacy and Safety of SABER®-Bupivacaine for Postoperative Pain Control in Patients Undergoing Hysterectomy

Study Overview
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Brief Summary
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The objective is to identify the optimal dose of SABER-Bupivacaine for postoperative pain control in patients undergoing hysterectomy on the basis of pharmacokinetics, efficacy and safety evaluations. The study duration consists of a screening period up to 14 days and a treatment period 14 days with a long term follow up visit at 6 months. The study will provide further data on the efficacy and safety of the product.

Official Title
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An International, Randomised, Double Blinded, Multi-centre, Active- and Placebo-controlled Dose Response Trial to Evaluate the Efficacy and Safety of SABER-Bupivacaine for Postoperative Pain Control in Patients Undergoing Primary, Elective, Open, Abdominal Hysterectomy

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: SABER-Bupivacaine Treatment 1a
* Drug: Placebo SABER-Bupivacaine Treatment 1b
* Drug: Bupivacaine HCl Treatment 1c
* Drug: SABER-Bupivacaine Treatment 2a
* Drug: Placebo SABER-Bupivacaine Treatment 2b
* Drug: Bupivacaine HCl Treatment 2c


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A planned elective, abdominal hysterectomy Patients suitable for general anaesthesia Exclusion Criteria: Known clinically significant hepatic, gastrointestinal, renal, haematological, urologic, neurological, respiratory, endocrine or cardiovascular system abnormalities Known serious uncontrolled illness: cancer, psychiatric or metabolic disturbances. History of cured localised malignancies is allowed (i.e. basal or squamous cell skin carcinoma, breast carcinoma or cervical carcinoma) Abnormal ECG Prolonged QT syndrome Current or regular use of analgesic medication for other indication(s)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SABER-Bupivacaine Treatment 1a<br>double-blind | Drug: SABER-Bupivacaine Treatment 1a<br>* 5.0 ml<br>|
| Placebo Comparator: Placebo SABER-Bupivacaine Treatment 1b<br>double-blind | Drug: Placebo SABER-Bupivacaine Treatment 1b<br>* 5.0 ml<br>* Other names: POSIMIR® bupivacaine solution;|
| Active Comparator: Bupivacaine HCl Treatment 1c<br>double-blind | Drug: Bupivacaine HCl Treatment 1c<br>* 40 ml<br>|
| Experimental: SABER-Bupivacaine Treatment 2a<br>double-blind | Drug: SABER-Bupivacaine Treatment 2a<br>* 7.5 ml<br>|
| Placebo Comparator: Placebo SABER-Bupivacaine Treatment 2b<br>double-blind | Drug: Placebo SABER-Bupivacaine Treatment 2b<br>* 7.5 ml<br>|
| Active Comparator: Bupivacaine HCl Treatment 2c<br>double-blind | Drug: Bupivacaine HCl Treatment 2c<br>* 40 ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity (PI) | Pain intensity (PI) on movement AUC over the period 1 to 72 hours post-surgery. Subjects assessed their pain intensity using an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) with NRS scores ranging from 0 (no pain) to 10 (worst pain possible). The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude. | 1 to 72 hours post-surgery | 
| Supplemental Opioid Use | Cumulative IV morphine-equivalent dose of opioid rescue medication | 0-3 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Opioid Rescue Medication Usage |  | 0-14 days after surgery | 
| Opioid Related Side Effects | Opioid-related side effects were recorded 0-7 days after surgery. The Opioid-Related Symptom Distress Scale (OR-SDS) is a composite score computed from a questionnaire containing frequent opioid-related symptoms (Fatigue, Drowsiness, Inability to concentrate, Nausea, Dizziness, Constipation, Itching, Difficulty with urination, Confusion, Retching/vomiting). For each symptom, patients assigned integer scores to assess severity (none=0 to very severe=4), bothersomeness (none=0 to very much=5), and frequency (none=0 to almost constantly=4); patients reported number of Retching/vomiting episodes (none=0, 1-2 episodes=1, 3-4 episodes=2, 5-6 episodes=3, >6 episodes=4). On each day (Day 0-7), the score for each symptom was the mean of the three component scores, and the OR-SDS score was the overall mean of the 10 symptom scores, (values from 0 to 4; larger outcomes are worse). The mean of the daily OR-SDS score from Day 0 to 7 gave the overall OR-SDS Score. | 0-7 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative pain, Local anaesthesia, Postoperative pain after open abdominal hysterectomy surgery