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

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Nycomed
• Germany
  • Bayreuth, Germany
    • Nycomed
  • Dresden, Germany
    • Nycomed
• Hungary
  • Budapest, Hungary
    • Nycomed
  • Békéscsaba, Hungary
    • Nycomed
  • Debrecen, Hungary
    • Nycomed
  • Györ, Hungary
    • Nycomed
  • Nyíregyháza, Hungary
    • Nycomed
  • Szolnok, Hungary
    • Nycomed
  • Székesfehérvár, Hungary
    • Nycomed
  • Tatabánya, Hungary
    • Nycomed
• Latvia
  • Riga, Latvia
    • Nycomed
• Sweden
  • Stockholm, Sweden
    • Nycomed
• United Kingdom
  • London, United Kingdom
    • Nycomed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Durect
• Collaborators: Nycomed

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: October 9, 2009
• First Submitted That Met QC Criteria: October 9, 2009
• First Posted (Estimate): October 12, 2009

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 7, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Postoperative pain; Local anaesthesia; Postoperative pain after open abdominal hysterectomy surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: BU-001-IM