Trial Outcomes & Findings for Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL, EXPAREL Admixed With Bupivacaine HCl vs. Bupivacaine HCl Administered as Combined Sciatic and Saphenous Nerve Blocks for Postsurgical Analgesia in Subjects Undergoing Lower Extremity Surgeries (NCT NCT04518462)

Last Updated: 2022-07-18

Results Overview

To compare the magnitude of the analgesic effect (NRS pain intensity scores) following a single dose injection of EXPAREL vs. bupivacaine hydrochloride (HCl) when administered as combined sciatic (in the popliteal fossa) and saphenous (in the adductor canal) nerve blocks in subjects undergoing lower extremity surgeries. Numerical Rating Scale: an 11 point scale 0=no pain, 10= the worst pain imaginable. The area under the curve (AUC) of the NRS pain intensity scores from 0 to 96 hours post-surgery comparing EXPAREL to 0.25% bupivacaine HCl

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

121 participants

Primary outcome timeframe

Post surgery - 96 hours

Results posted on

2022-07-18

Participant Flow

Participant milestones

Participant milestones
Measure	EXPAREL Arm Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine
Overall Study STARTED	40	41	40
Overall Study COMPLETED	39	40	39
Overall Study NOT COMPLETED	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	EXPAREL Arm Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine
Overall Study Withdrawal by Subject	0	0	1
Overall Study Physician Decision	1	1	0

Baseline Characteristics

Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL, EXPAREL Admixed With Bupivacaine HCl vs. Bupivacaine HCl Administered as Combined Sciatic and Saphenous Nerve Blocks for Postsurgical Analgesia in Subjects Undergoing Lower Extremity Surgeries

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EXPAREL Arm n=39 Participants Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm n=40 Participants subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm n=40 Participants subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine	Total n=119 Participants Total of all reporting groups
Sex: Female, Male Female	35 Participants n=93 Participants	36 Participants n=4 Participants	27 Participants n=27 Participants	98 Participants n=483 Participants
Age, Customized <45 years	11 Participants n=93 Participants	14 Participants n=4 Participants	18 Participants n=27 Participants	43 Participants n=483 Participants
Age, Customized >/=45 years	28 Participants n=93 Participants	26 Participants n=4 Participants	22 Participants n=27 Participants	76 Participants n=483 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	4 Participants n=4 Participants	13 Participants n=27 Participants	21 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=93 Participants	12 Participants n=4 Participants	15 Participants n=27 Participants	37 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=93 Participants	26 Participants n=4 Participants	25 Participants n=27 Participants	79 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	4 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants	11 Participants n=4 Participants	7 Participants n=27 Participants	23 Participants n=483 Participants
Race (NIH/OMB) White	32 Participants n=93 Participants	26 Participants n=4 Participants	30 Participants n=27 Participants	88 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
American Society of Anesthesiologists (ASA) Classification ASA 1	15 Participants n=93 Participants	12 Participants n=4 Participants	23 Participants n=27 Participants	50 Participants n=483 Participants
American Society of Anesthesiologists (ASA) Classification ASA 2	24 Participants n=93 Participants	26 Participants n=4 Participants	17 Participants n=27 Participants	67 Participants n=483 Participants
American Society of Anesthesiologists (ASA) Classification ASA 3	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
American Society of Anesthesiologists (ASA) Classification ASA >/= 4	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Height <165 cm	20 participants n=93 Participants	21 participants n=4 Participants	20 participants n=27 Participants	61 participants n=483 Participants
Height >/= 165 cm	19 participants n=93 Participants	19 participants n=4 Participants	20 participants n=27 Participants	58 participants n=483 Participants
Weight	77.05 kg n=93 Participants	83.03 kg n=4 Participants	77.34 kg n=27 Participants	79.16 kg n=483 Participants
Body Mass Index (BMI) kg/m2 <25 kg/m2	10 participants n=93 Participants	9 participants n=4 Participants	10 participants n=27 Participants	29 participants n=483 Participants
Body Mass Index (BMI) kg/m2 25- <30kg/m2	15 participants n=93 Participants	10 participants n=4 Participants	19 participants n=27 Participants	44 participants n=483 Participants
Body Mass Index (BMI) kg/m2 >/= 30 kg/m2	14 participants n=93 Participants	21 participants n=4 Participants	11 participants n=27 Participants	46 participants n=483 Participants
Average and worst pain intensity score (NRS) in the last 30 days average NRS	2.3 score on a scale STANDARD_DEVIATION 2.53 • n=93 Participants	3.2 score on a scale STANDARD_DEVIATION 2.94 • n=4 Participants	2.2 score on a scale STANDARD_DEVIATION 2.24 • n=27 Participants	2.6 score on a scale STANDARD_DEVIATION 2.60 • n=483 Participants
Average and worst pain intensity score (NRS) in the last 30 days worst NRS	3.3 score on a scale STANDARD_DEVIATION 2.64 • n=93 Participants	4.5 score on a scale STANDARD_DEVIATION 3.14 • n=4 Participants	3.3 score on a scale STANDARD_DEVIATION 2.76 • n=27 Participants	3.7 score on a scale STANDARD_DEVIATION 2.88 • n=483 Participants
Pain Catastrophizing Scale Total Score	11.7 score on a scale STANDARD_DEVIATION 11.49 • n=93 Participants	13.4 score on a scale STANDARD_DEVIATION 11.91 • n=4 Participants	11.0 score on a scale STANDARD_DEVIATION 10.68 • n=27 Participants	12.0 score on a scale STANDARD_DEVIATION 11.32 • n=483 Participants

PRIMARY outcome

Timeframe: Post surgery - 96 hours

Outcome measures

Outcome measures
Measure	EXPAREL Arm n=39 Participants Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm n=40 Participants subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm n=40 Participants subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine
Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC)	298.65 score on a scale*hours Standard Deviation 173.524	358.10 score on a scale*hours Standard Deviation 223.610	380.05 score on a scale*hours Standard Deviation 220.878

SECONDARY outcome

Timeframe: 0 hours to 96 hours

Total Opioid Consumption in oral morphine equivalents

Outcome measures

Outcome measures
Measure	EXPAREL Arm n=39 Participants Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm n=40 Participants subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm n=40 Participants subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine
Total Opioid Consumption	20.68 OMED mg Interval 13.51 to 31.65	23.56 OMED mg Interval 15.54 to 35.73	19.84 OMED mg Interval 12.72 to 30.96

SECONDARY outcome

Timeframe: Post Surgery through Day 14

Time to First Opioid following a single dose of EXPAREL vs. Bupivacain HCl

Outcome measures

Outcome measures
Measure	EXPAREL Arm n=39 Participants Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm n=40 Participants subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm n=40 Participants subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine
Time to First Opioid	5.65 hours Interval 0.72 to 13.55	11.93 hours Interval 5.15 to 16.28	16.67 hours Interval 7.53 to 22.33

Adverse Events

EXPAREL Arm

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

EXPAREL Admix Arm

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Bupivacaine HCl Arm

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pacira Medical Information

Pacira Pharmaceuticals, Inc.

Phone: 1-855-793-9729

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results conducted at Site shall not be published before 1st multicenter publication by Sponsor but can proceed if there is no such publication \</= 18 months after study completion/termination at all sites and all data have been received. Before submitting manuscript/materials to an outside person/entity, site shall give Sponsor 60 days to review and comment. Site shall, upon request, further delay publication/presentation for \</=120 days to allow Sponsor to protect its interests in Inventions.
Publication restrictions are in place

Restriction type: OTHER

Measure	EXPAREL Arm n=39 participants at risk Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension)	EXPAREL Admix Arm n=41 participants at risk subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. EXPAREL (bupivacaine liposome injectable suspension) Bupivacaine Hydrochloride: 0.25% bupivacaine	Bupivacaine HCl Arm n=39 participants at risk subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine
Gastrointestinal disorders Constipation	23.1% 9/39 • Number of events 9 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	26.8% 11/41 • Number of events 11 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	28.2% 11/39 • Number of events 11 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Gastrointestinal disorders Nausea	20.5% 8/39 • Number of events 11 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	29.3% 12/41 • Number of events 14 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	17.9% 7/39 • Number of events 7 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Gastrointestinal disorders Vomiting	2.6% 1/39 • Number of events 3 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	14.6% 6/41 • Number of events 8 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
General disorders Pyrexia	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	0.00% 0/41 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.6% 1/39 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Investigations Blood Pressure Increased	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	4.9% 2/41 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.6% 1/39 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	0.00% 0/41 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.6% 1/39 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Nervous system disorders Dizziness	7.7% 3/39 • Number of events 3 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	4.9% 2/41 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Nervous system disorders Headache	25.6% 10/39 • Number of events 10 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	9.8% 4/41 • Number of events 5 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	17.9% 7/39 • Number of events 7 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Nervous system disorders Hypoaesthesia	20.5% 8/39 • Number of events 8 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	22.0% 9/41 • Number of events 9 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	0.00% 0/39 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Nervous system disorders Motor dysfuction	2.6% 1/39 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Nervous system disorders Paraesthesia	12.8% 5/39 • Number of events 8 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	7.3% 3/41 • Number of events 6 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	28.2% 11/39 • Number of events 12 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/39 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	0.00% 0/41 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	0.00% 0/41 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	0.00% 0/39 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.6% 1/39 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	5.1% 2/39 • Number of events 2 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.
Skin and subcutaneous tissue disorders Pruritis	7.7% 3/39 • Number of events 3 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.	2.6% 1/39 • Number of events 1 • Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14.