Trial Outcomes & Findings for Phase 3 Adductor Canal Block With EXPAREL in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty (NCT NCT05139030)

Last Updated: 2024-10-24

Results Overview

The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point: 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

167 participants

Primary outcome timeframe

0 to 96 hours post-surgery

Results posted on

2024-10-24

Participant Flow

Participants were recruited based on physician referral at 6 sites between January 2022 and July 2022. The first participant was enrolled on January 18, 2022 and the last participant was enrolled in June 08, 2022.

Of 340 screened participants, 167 met inclusion criteria and were randomized to treatment within Cohort 1 or Cohort 2. Overall results are presented per treatment arm including participants from both cohorts 1 + 2

Participant milestones

Participant milestones
Measure	Cohort 1 + 2: EXPAREL Admix Arm subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl bupivacaine liposome injectable suspension: Adductor canal block with EXPAREL	Cohort 1 + 2: Bupivacaine HCl Arm subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine hydrochloric acid (HCl) mixed with 10 mL normal saline Bupivacaine Hydrochloride: Adductor Canal Block with bupivacaine HCl
Overall Study STARTED	85	82
Overall Study COMPLETED	84	77
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 + 2: EXPAREL Admix Arm subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl bupivacaine liposome injectable suspension: Adductor canal block with EXPAREL	Cohort 1 + 2: Bupivacaine HCl Arm subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine hydrochloric acid (HCl) mixed with 10 mL normal saline Bupivacaine Hydrochloride: Adductor Canal Block with bupivacaine HCl
Overall Study Withdrawal by Subject	1	3
Overall Study Adverse Event	0	1
Overall Study Failure to meet continuation criteria	0	1

Baseline Characteristics

Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 + 2: EXPAREL Admix Arm n=85 Participants subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl bupivacaine liposome injectable suspension: Adductor canal block with EXPAREL	Cohort 1 + 2: Bupivacaine HCl Arm n=81 Participants subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline Bupivacaine Hydrochloride: Adductor Canal Block with bupivacaine HCl	Total n=166 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	0 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	0 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Age, Categorical Between 18 and 65 years	54 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	53 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	107 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Age, Categorical >=65 years	31 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	28 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	59 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Age, Continuous	62.00 years STANDARD_DEVIATION 7.049 • n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	62.21 years STANDARD_DEVIATION 8.402 • n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	62.10 years STANDARD_DEVIATION 7.716 • n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Sex: Female, Male Female	42 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	39 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	81 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Sex: Female, Male Male	43 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	42 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	85 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=93 Participants	12 Participants n=4 Participants	33 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=93 Participants	66 Participants n=4 Participants	130 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Race · White	67 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	63 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	130 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Race/Ethnicity, Customized Race · Black/African American	14 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	15 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	29 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Race/Ethnicity, Customized Race · Other	4 Participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	3 Participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	7 Participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
Region of Enrollment United States	85 participants n=93 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	81 participants n=4 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone	166 participants n=27 Participants • Results presented are the combined participants of cohort 1 + cohort 2 treated with EXPAREL admixed with bupivacaiane HC1 and the combined participants of cohort 1 + cohort 2 treated with bupivacine HCI alone
ASA classification ASA 1	21 Participants n=93 Participants	21 Participants n=4 Participants	42 Participants n=27 Participants
ASA classification ASA 2	62 Participants n=93 Participants	56 Participants n=4 Participants	118 Participants n=27 Participants
ASA classification ASA 3	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
ASA classification Unknown	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Body Mass Index	31.43 kilograms/m^2 STANDARD_DEVIATION 4.786 • n=93 Participants	32.74 kilograms/m^2 STANDARD_DEVIATION 4.955 • n=4 Participants	32.07 kilograms/m^2 STANDARD_DEVIATION 4.899 • n=27 Participants
Body mass index, categorical <25 kg/m^2	5 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants
Body mass index, categorical 25 to <30 kg/m^2	32 Participants n=93 Participants	14 Participants n=4 Participants	46 Participants n=27 Participants
Body mass index, categorical >=30 kg/m^2	48 Participants n=93 Participants	60 Participants n=4 Participants	108 Participants n=27 Participants
Worst pain intensity (NRS)	7.2 units on a scale STANDARD_DEVIATION 2.03 • n=93 Participants	7.4 units on a scale STANDARD_DEVIATION 2.32 • n=4 Participants	7.3 units on a scale STANDARD_DEVIATION 2.17 • n=27 Participants
Average pain intensity (NRS)	5.2 units on a scale STANDARD_DEVIATION 2.32 • n=93 Participants	5.3 units on a scale STANDARD_DEVIATION 2.22 • n=4 Participants	5.2 units on a scale STANDARD_DEVIATION 2.27 • n=27 Participants

PRIMARY outcome

Timeframe: 0 to 96 hours post-surgery

Population: The analysis was performed on the efficacy analysis set which included all participants in the safety analysis set who underwent the planned surgery and had at least one post-drug administration NRS pain assessment. Results presented correspond to the combined population for cohorts 1 + 2 of each treatment arm

Outcome measures

Outcome measures
Measure	Cohort 1 + 2 EXPAREL ADMIX ARM n=85 Participants Subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine hydrochloric acid (HCI) Bupivacaine liposome injectable suspension Adductor canal block with EXPAREL	Cohort 1 + 2 BUPIVACAINE HCI ARM n=81 Participants Subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCI mixed with 10 mL normal saline Bupivacaine Hydrochloride Adductor Canal Block with bupivacaine HCI
NRS Scores Through 96 Hours Post-surgery	594.4 units on a scale*hours Standard Deviation 191.65	650.1 units on a scale*hours Standard Deviation 178.95

SECONDARY outcome

Timeframe: 0 to 96 hours post-surgery

Total postsurgical opioid consumption in mg oral morphine equivalents (OMED) from 0 to 96 hours post-surgery.

Outcome measures

Outcome measures
Measure	Cohort 1 + 2 EXPAREL ADMIX ARM n=85 Participants Subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine hydrochloric acid (HCI) Bupivacaine liposome injectable suspension Adductor canal block with EXPAREL	Cohort 1 + 2 BUPIVACAINE HCI ARM n=81 Participants Subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCI mixed with 10 mL normal saline Bupivacaine Hydrochloride Adductor Canal Block with bupivacaine HCI
Postsurgical Opioid Consumption Through 96 Hours Post-surgery	109.19 milligrams oral morphine equivalents Geometric Coefficient of Variation 54.420	136.91 milligrams oral morphine equivalents Geometric Coefficient of Variation 48.284

SECONDARY outcome

Timeframe: 0 to 96 hours post-surgery

Time to first opioid consumption post-surgery

Outcome measures

Outcome measures
Measure	Cohort 1 + 2 EXPAREL ADMIX ARM n=85 Participants Subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine hydrochloric acid (HCI) Bupivacaine liposome injectable suspension Adductor canal block with EXPAREL	Cohort 1 + 2 BUPIVACAINE HCI ARM n=81 Participants Subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCI mixed with 10 mL normal saline Bupivacaine Hydrochloride Adductor Canal Block with bupivacaine HCI
Time to First Opioid	4.15 hours Interval 3.8 to 4.83	3.63 hours Interval 2.98 to 4.05

SECONDARY outcome

Timeframe: 0-24hours, 24-48hours, 48-72hours, 72-96hours

Population: The superiority of EXPAREL admixed to bupivacaine HCI was evaluated using the Efficacy Analysis Set with the worst observation carried forward (WOCF)/interpolation method. A one-sided hypothesis test was performed at alpha=0.025 level of significance comparing EXPAREL admix and bupivacaine HCI. The number analyzed in one or more rows differs from overall number analyzed due to participant discontinuation in bupivacaine HCI arm and a missed assessment (protocol deviation) in EXPAREL admix arm.

Worst and average NRS pain intensity scores at 24h, 48h, 72h and 96h from the end of surgery Worst and average pain intensity scores on a numeric rating scale ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours. Mean scores at each timepoint are provided. The total range is 0 (no pain) to 10 (worst possible pain). Higher values on the scale represent worst outcome

Outcome measures

Outcome measures
Measure	Cohort 1 + 2 EXPAREL ADMIX ARM n=85 Participants Subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine hydrochloric acid (HCI) Bupivacaine liposome injectable suspension Adductor canal block with EXPAREL	Cohort 1 + 2 BUPIVACAINE HCI ARM n=81 Participants Subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCI mixed with 10 mL normal saline Bupivacaine Hydrochloride Adductor Canal Block with bupivacaine HCI
NRS Scores Worst pain at 72 hours	6.8 units on a scale Standard Deviation 2.33	7.5 units on a scale Standard Deviation 2.14
NRS Scores Worst pain at 96 hours	6.6 units on a scale Standard Deviation 2.24	7.0 units on a scale Standard Deviation 2.34
NRS Scores Average pain at 24 hours	6.7 units on a scale Standard Deviation 1.89	6.6 units on a scale Standard Deviation 2.00
NRS Scores Average pain at 96 hours	4.8 units on a scale Standard Deviation 2.18	5.2 units on a scale Standard Deviation 1.96
NRS Scores Worst pain at 24 hours	8.6 units on a scale Standard Deviation 1.63	8.7 units on a scale Standard Deviation 1.77
NRS Scores Worst pain at 48 hours	7.9 units on a scale Standard Deviation 1.98	8.2 units on a scale Standard Deviation 1.81
NRS Scores Average pain at 48 hours	5.8 units on a scale Standard Deviation 2.03	6.2 units on a scale Standard Deviation 1.84
NRS Scores Average pain at 72 hours	5.2 units on a scale Standard Deviation 2.14	5.7 units on a scale Standard Deviation 2.08

Adverse Events

Cohort 1 + 2 EXPAREL ADMIX ARM

Serious events: 3 serious events

Other events: 77 other events

Deaths: 0 deaths

Cohort 1 + 2 BUPIVACAINE HCI ARM

Serious events: 3 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 + 2 EXPAREL ADMIX ARM n=85 participants at risk Subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCI Bupivacaine liposome injectable suspension Adductor canal block with EXPAREL	Cohort 1 + 2 BUPIVACAINE HCI ARM n=81 participants at risk Subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCI mixed with 10 mL normal saline Bupivacaine Hydrochloride Adductor Canal Block with bupivacaine HCI
Cardiac disorders Acute myocardial infarction	0.00% 0/85 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Cardiac disorders Atrial fibrillation	0.00% 0/85 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Cardiac disorders Tachycardia	1.2% 1/85 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	0.00% 0/81 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Infections and infestations Pneumonia	1.2% 1/85 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	0.00% 0/81 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Injury, poisoning and procedural complications Post procedural haematoma	1.2% 1/85 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	0.00% 0/81 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/85 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/85 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit

Other adverse events

Other adverse events
Measure	Cohort 1 + 2 EXPAREL ADMIX ARM n=85 participants at risk Subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCI Bupivacaine liposome injectable suspension Adductor canal block with EXPAREL	Cohort 1 + 2 BUPIVACAINE HCI ARM n=81 participants at risk Subjects randomized to this treatment arm received 10 mL (50 mg) 0.5% bupivacaine HCI mixed with 10 mL normal saline Bupivacaine Hydrochloride Adductor Canal Block with bupivacaine HCI
Gastrointestinal disorders Nausea	40.0% 34/85 • Number of events 36 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	37.0% 30/81 • Number of events 32 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Gastrointestinal disorders Constipation	35.3% 30/85 • Number of events 31 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	38.3% 31/81 • Number of events 31 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Gastrointestinal disorders Vomiting	5.9% 5/85 • Number of events 5 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	7.4% 6/81 • Number of events 7 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Musculoskeletal and connective tissue disorders Muscle spasms	12.9% 11/85 • Number of events 12 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	11.1% 9/81 • Number of events 10 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Psychiatric disorders Insomnia	5.9% 5/85 • Number of events 5 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	16.0% 13/81 • Number of events 14 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Nervous system disorders Headache	15.3% 13/85 • Number of events 14 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	2.5% 2/81 • Number of events 3 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Vascular disorders Hypotension	3.5% 3/85 • Number of events 4 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	9.9% 8/81 • Number of events 8 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Vascular disorders Hypertension	5.9% 5/85 • Number of events 5 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	4.9% 4/81 • Number of events 4 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Skin and subcutaneous tissue disorders Pruritus	7.1% 6/85 • Number of events 6 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	4.9% 4/81 • Number of events 4 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit
Cardiac disorders Tachycardia	4.7% 4/85 • Number of events 5 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit	6.2% 5/81 • Number of events 6 • Treatment-emergent adverse events were collected from the date and time on or after the start date and time of study drug administration through post-operative Day 14 Participants were expected to volunteer information about adverse events that they experienced. In addition, the investigator or designee questioned the patient at each scheduled time point/visit about adverse events and recorded these as well as other adverse events at the time point/visit

Additional Information

Pacira Medical Information

Pacira Pharmaceuticals, Inc.

Phone: 1-855-793-9727

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Disclosure restrictions include: * PIs or any other party are not allowed to publish any publication for a period of twelve months following completion of the clinical study report for the trial. * PIs or any other party shall submit a proposal to the Sponsor for approval to obtain trial results that have not been previously made public and any publication, abstract or paper or other written materials to the trial shall be submitted to the Sponsor at least 60 days prior to submission.
Publication restrictions are in place

Restriction type: OTHER