Trial Outcomes & Findings for Trial of Extended Release Bupivacaine for Pain Relief After Surgery (NCT NCT02574520)

Last Updated: 2021-07-13

Results Overview

A derived measure computed based on a patient-reported numerical pain rating scale assessing pain as a whole number from 0 (no pain) to 10 (worst pain imaginable) when the subject sits up from a supine position. This measure was evaluated by electronic diary at 13 planned time points from 0 to 48 hours post-treatment. The values reported are mean pain scores for each treatment group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

399 participants

Primary outcome timeframe

Assessed from 0 to 48 hours post-dose, summary measure (see description) reported.

Results posted on

2021-07-13

Participant Flow

The study was conducted at 22 sites in the US. First subject was randomized on 17 November 2015. Study completion date was on 16 Aug 2017.

Participant milestones

Participant milestones
Measure	SABER-Bupivacaine (Part 1) 5 ml once at end of surgery	Saline Placebo (Part 1) 5 ml once at end of surgery	SABER-Bupivacaine (Part 2) 5 ml once at end of surgery	Bupivacaine HCL (Part 2) 0.5%, 15 ml, once at end of surgery
Overall Study STARTED	48	46	153	152
Overall Study Dosed	46	46	148	148
Overall Study COMPLETED	46	46	148	144
Overall Study NOT COMPLETED	2	0	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	SABER-Bupivacaine (Part 1) 5 ml once at end of surgery	SABER-Bupivacaine (Part 2) 5 ml once at end of surgery	Bupivacaine HCL (Part 2) 0.5%, 15 ml, once at end of surgery
Overall Study Not dosed	2	5	4
Overall Study Adverse Event	0	0	1
Overall Study Withdrawal by Subject	0	0	1
Overall Study Other	0	0	2

Baseline Characteristics

Trial of Extended Release Bupivacaine for Pain Relief After Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SABER-Bupivacaine (Part 1) n=48 Participants 5 ml once at end of surgery	Saline Placebo (Part 1) n=46 Participants 5 ml once at end of surgery	SABER-Bupivacaine (Part 2) n=153 Participants 5 ml once at end of surgery	Bupivacaine HCL (Part 2) n=152 Participants 0.5%, 15 ml, once at end of surgery	Total n=399 Participants Total of all reporting groups
Sex: Female, Male Female	31 Participants n=5 Participants	29 Participants n=7 Participants	115 Participants n=5 Participants	117 Participants n=4 Participants	292 Participants n=21 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants	35 Participants n=4 Participants	107 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	26 Participants n=21 Participants
Age, Continuous	46.0 years STANDARD_DEVIATION 14.2 • n=5 Participants	41.8 years STANDARD_DEVIATION 12.8 • n=7 Participants	45.5 years STANDARD_DEVIATION 13.5 • n=5 Participants	44.7 years STANDARD_DEVIATION 13.9 • n=4 Participants	44.8 years STANDARD_DEVIATION 13.67 • n=21 Participants
Race (NIH/OMB) White	39 Participants n=5 Participants	40 Participants n=7 Participants	141 Participants n=5 Participants	135 Participants n=4 Participants	355 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Region of Enrollment United States	48 participants n=5 Participants	46 participants n=7 Participants	153 participants n=5 Participants	152 participants n=4 Participants	399 participants n=21 Participants

PRIMARY outcome

Timeframe: Assessed from 0 to 48 hours post-dose, summary measure (see description) reported.

Population: mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 2) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified primary outcome measure that included the SABER-Bupivacaine (Part 1) arm or the Saline Placebo (Part 1) arm.

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=148 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Pain Intensity on Movement From 0-48 Hours Post-Treatment	5.55 score on a scale Standard Error 0.065	5.87 score on a scale Standard Error 0.059

SECONDARY outcome

Timeframe: Assessed from 0 to 72 hours post-dose, summary measure (see description) reported.

Population: mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

A derived measure computed based on a patient-reported numerical pain rating scale assessing pain as a whole number from 0 (no pain) to 10 (worst pain imaginable) when the subject sits up from a supine position. This measure was evaluated by electronic diary at 17 planned time points from 0 to 72 hours post-treatment. The values reported are mean pain scores for each treatment group.

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=194 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Pain Intensity Using the NPRS-11 With Movement	4.94 score on a scale Standard Error 0.049	5.40 score on a scale Standard Error 0.052

SECONDARY outcome

Timeframe: 0-72 hrs. post dose (after surgery)

IV morphine-equivalent dose

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=194 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Total IV Morphine-equivalent Dose of Rescue Opioids	21.4 IV morphine equivalent (mg) Standard Error 1.37	22.6 IV morphine equivalent (mg) Standard Error 1.58

SECONDARY outcome

Timeframe: 0 to 72 hours

Score of Integrated Analgesia (SIA) is a composite endpoint that integrates pain assessment scores with opioid use over various collections of timepoints by ranking the pain score and the opioid use separately across treatments. After the scores are computed the means are calculated across time points to provide a single overall treatment effect. The composite SIA score ranges from -200 to 200 with -200 being the best case and 200 the worst case.

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=194 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Composite Endpoint of Silverman's Integrated Analgesic (SIA) Assessment Score	-17.3 score on a scale Standard Error 8.83	-1.5 score on a scale Standard Error 9.33

SECONDARY outcome

Timeframe: From PACU Discharge to 72 Hours post-treatment

Pooled SABER-Bupivacaine parts 1 + 2 vs. Bupivacaine HCl

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=194 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Subjects Not Taking Rescue Medication From PACU Discharge to 72 Hours	57 participants	42 participants

SECONDARY outcome

Timeframe: From PACU Discharge to 72 Hours post-treatment

Pooled SABER-Bupivacaine parts 1 + 2 vs. Bupivacaine HCl

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=194 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Time to First Opioid Rescue Medication Use After Discharge From the PACU	5.5 hours Interval 3.5 to 7.7	6.1 hours Interval 3.3 to 9.0

SECONDARY outcome

Timeframe: From admission to discharge from PACU (Approximately 0 to 12 hours)

mPADSS is a tool used to determine eligibility for discharge from the PACU after ambulatory surgery. It includes an assessment of parameters such as vital signs, activity level, nausea/vomiting, pain, and surgical bleeding. For this trial, evaluation of eligibility for PACU discharge by mPADSS has been slightly modified to provide a standardized means of assessing eligibility for PACU discharge across multiple investigative sites and also ensures that nonmedical complications, such as a missing ride home, do not interfere with evaluation of test drug effects.

Outcome measures

Outcome measures
Measure	Part 2/SABER-Bupivacaine n=194 Participants 5 ml once at end of surgery	Part 2/Bupivacaine HCl n=148 Participants 0.5%, 15 ml, once at end of surgery
Time to PACU Discharge Eligibility as Assessed by Modified Post-Anesthesia Discharge Scoring System (mPADSS)	1.8 hours Interval 1.8 to 1.9	1.9 hours Interval 1.8 to 2.0

Adverse Events

SABER-Bupivacaine (Part 1)

Serious events: 1 serious events

Other events: 43 other events

Deaths: 0 deaths

Saline Placebo (Part 1)

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

SABER-Bupivacaine (Part 2)

Serious events: 5 serious events

Other events: 148 other events

Deaths: 0 deaths

Bupivacaine HCL (Part 2)

Serious events: 3 serious events

Other events: 146 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SABER-Bupivacaine (Part 1) n=45 participants at risk 5 ml once at end of surgery	Saline Placebo (Part 1) n=47 participants at risk 5 ml once at end of surgery	SABER-Bupivacaine (Part 2) n=148 participants at risk 5 ml once at end of surgery	Bupivacaine HCL (Part 2) n=148 participants at risk 0.5%, 15 ml, once at end of surgery
Infections and infestations Abdominal abscess	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Hepatobiliary disorders Bile duct stone	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Metabolism and nutrition disorders Dehydration	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Nervous system disorders Dizziness	2.2% 1/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Gastrointestinal disorders Gastritis	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Investigations Hepatic enzyme increased	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Vascular disorders Hypotension	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Gastrointestinal disorders Pancreatitis	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Gastrointestinal disorders Pancreatitis acute	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Injury, poisoning and procedural complications Post procedural bile leak	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/45 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/47 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.68% 1/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)	0.00% 0/148 • Approximately 0-60 days after surgery (duration of time over which each participant was assessed). Systematic and Non-systematic reported TEAEs of \>5% (Safety Population)

Other adverse events

Additional Information

Deborah Scott

Durect Corporation

Phone: 408-777-1417

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place