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

Phase 2

Completed

Interventions: Drug: SABER-Bupivacaine Treatment 2a
Drug: Placebo SABER-Bupivacaine Treatment 2b
Drug: SABER-Bupivacaine Treatment 1a
Drug: Placebo SABER-Bupivacaine Treatment 1b
Drug: Bupivacaine HCl Treatment 2c
Drug: Bupivacaine HCl Treatment 1c

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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)

Arm && Interventions

Group	Intervention	Description
SABER-Bupivacaine Treatment 2a	SABER-Bupivacaine Treatment 2a	double-blind
Placebo SABER-Bupivacaine Treatment 2b	Placebo SABER-Bupivacaine Treatment 2b	double-blind
SABER-Bupivacaine Treatment 1a	SABER-Bupivacaine Treatment 1a	double-blind
Placebo SABER-Bupivacaine Treatment 1b	Placebo SABER-Bupivacaine Treatment 1b	double-blind
Bupivacaine HCl Treatment 2c	Bupivacaine HCl Treatment 2c	double-blind
Bupivacaine HCl Treatment 1c	Bupivacaine HCl Treatment 1c	double-blind

Primary Outcome Measures

Name	Time	Method
Supplemental Opioid Use	0-3 days after surgery	Cumulative IV morphine-equivalent dose of opioid rescue medication
Pain Intensity (PI)	1 to 72 hours post-surgery	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.

Secondary Outcome Measures

Name	Time	Method
Time to First Opioid Rescue Medication Usage	0-14 days after surgery
Opioid Related Side Effects	0-7 days after surgery	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.