Trial Outcomes & Findings for Phase 3 Herniorrhaphy Study for Postoperative Analgesia (EPOCH 2) (NCT NCT03237481)

Last Updated: 2026-03-02

Results Overview

Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720. The prescribed activity for NRS-A is sitting up from a resting position.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

418 participants

Primary outcome timeframe

72 hours

Results posted on

2026-03-02

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Group 1: HTX-011 HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.	Treatment Group 2: Bupivacaine HCI Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 3: Saline Placebo Saline Placebo by instillation.
Overall Study STARTED	164	172	82
Overall Study COMPLETED	159	170	81
Overall Study NOT COMPLETED	5	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Group 1: HTX-011 HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.	Treatment Group 2: Bupivacaine HCI Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 3: Saline Placebo Saline Placebo by instillation.
Overall Study Lost to Follow-up	1	0	0
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	3	2	1

Baseline Characteristics

Phase 3 Herniorrhaphy Study for Postoperative Analgesia (EPOCH 2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Group 1: HTX-011 n=164 Participants HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.	Treatment Group 2: Bupivacaine HCI n=172 Participants Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 3: Saline Placebo n=82 Participants Saline Placebo by instillation.	Total n=418 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants	0 Participants n=565 Participants
Age, Categorical Between 18 and 65 years	149 Participants n=41 Participants	161 Participants n=35 Participants	77 Participants n=76 Participants	387 Participants n=565 Participants
Age, Categorical >=65 years	15 Participants n=41 Participants	11 Participants n=35 Participants	5 Participants n=76 Participants	31 Participants n=565 Participants
Age, Continuous	48.9 years STANDARD_DEVIATION 13.29 • n=41 Participants	49.4 years STANDARD_DEVIATION 11.26 • n=35 Participants	48.0 years STANDARD_DEVIATION 14.59 • n=76 Participants	48.9 years STANDARD_DEVIATION 12.75 • n=565 Participants
Sex: Female, Male Female	12 Participants n=41 Participants	8 Participants n=35 Participants	3 Participants n=76 Participants	23 Participants n=565 Participants
Sex: Female, Male Male	152 Participants n=41 Participants	164 Participants n=35 Participants	79 Participants n=76 Participants	395 Participants n=565 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	43 Participants n=41 Participants	51 Participants n=35 Participants	30 Participants n=76 Participants	124 Participants n=565 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=41 Participants	121 Participants n=35 Participants	52 Participants n=76 Participants	294 Participants n=565 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants	0 Participants n=565 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants	2 Participants n=565 Participants
Race (NIH/OMB) Asian	2 Participants n=41 Participants	2 Participants n=35 Participants	1 Participants n=76 Participants	5 Participants n=565 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=41 Participants	1 Participants n=35 Participants	0 Participants n=76 Participants	5 Participants n=565 Participants
Race (NIH/OMB) Black or African American	17 Participants n=41 Participants	16 Participants n=35 Participants	3 Participants n=76 Participants	36 Participants n=565 Participants
Race (NIH/OMB) White	139 Participants n=41 Participants	153 Participants n=35 Participants	78 Participants n=76 Participants	370 Participants n=565 Participants
Race (NIH/OMB) More than one race	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants	0 Participants n=565 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=76 Participants	0 Participants n=565 Participants
Region of Enrollment Belgium	4 participants n=41 Participants	0 participants n=35 Participants	0 participants n=76 Participants	4 participants n=565 Participants
Region of Enrollment United States	160 participants n=41 Participants	172 participants n=35 Participants	82 participants n=76 Participants	414 participants n=565 Participants

PRIMARY outcome

Timeframe: 72 hours

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Treatment Group 2: Bupivacaine HCI n=82 Participants Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 1: HTX-011 n=164 Participants HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.	350.82 pain intensity score*hr Standard Deviation 171.224	269.39 pain intensity score*hr Standard Deviation 173.719

SECONDARY outcome

Timeframe: 72 hours

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Treatment Group 2: Bupivacaine HCI n=172 Participants Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 1: HTX-011 n=164 Participants HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.	341.88 pain intensity score*hr Standard Deviation 158.303	269.39 pain intensity score*hr Standard Deviation 173.719

SECONDARY outcome

Timeframe: 72 hours

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Treatment Group 2: Bupivacaine HCI n=82 Participants Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 1: HTX-011 n=164 Participants HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.	17.53 IV milligram morphine equivalent (MME) Standard Deviation 18.908	10.85 IV milligram morphine equivalent (MME) Standard Deviation 17.062

SECONDARY outcome

Timeframe: 72 hours

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Treatment Group 2: Bupivacaine HCI n=172 Participants Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 1: HTX-011 n=164 Participants HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.
Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.	69 Participants	84 Participants

SECONDARY outcome

Timeframe: 72 hours

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Treatment Group 2: Bupivacaine HCI n=172 Participants Bupivacaine HCl without epinephrine, 75 mg by injection.	Treatment Group 1: HTX-011 n=164 Participants HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.	14.51 IV milligram morphine equivalent (MME) Standard Deviation 18.185	10.85 IV milligram morphine equivalent (MME) Standard Deviation 17.062

Adverse Events

Treatment Group 1: HTX-011

Serious events: 2 serious events

Other events: 84 other events

Deaths: 0 deaths

Treatment Group 2: Bupivacaine HCI

Serious events: 1 serious events

Other events: 104 other events

Deaths: 0 deaths

Treatment Group 3: Saline Placebo

Serious events: 1 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Group 1: HTX-011 n=163 participants at risk HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.	Treatment Group 2: Bupivacaine HCI n=173 participants at risk Bupivacaine HCl without epinephrine, 75 mg by injection. 173 = Safety Population because 1 subject was randomized to HTX-011, but received bupivacaine HCl.	Treatment Group 3: Saline Placebo n=82 participants at risk Saline Placebo by instillation.
Infections and infestations Cellulitis of male external genital organ	0.00% 0/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	1.2% 1/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Infections and infestations Postoperative wound infection	0.00% 0/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	1.2% 1/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.61% 1/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
General disorders Pyrexia	0.00% 0/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.58% 1/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Injury, poisoning and procedural complications Incision site haematoma	0.61% 1/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Gastrointestinal disorders Inguinal hernia, obstructive	0.00% 0/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.00% 0/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	1.2% 1/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.

Other adverse events

Other adverse events
Measure	Treatment Group 1: HTX-011 n=163 participants at risk HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation.	Treatment Group 2: Bupivacaine HCI n=173 participants at risk Bupivacaine HCl without epinephrine, 75 mg by injection. 173 = Safety Population because 1 subject was randomized to HTX-011, but received bupivacaine HCl.	Treatment Group 3: Saline Placebo n=82 participants at risk Saline Placebo by instillation.
Gastrointestinal disorders Nausea	18.4% 30/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	21.4% 37/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	34.1% 28/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Gastrointestinal disorders Constipation	17.2% 28/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	23.7% 41/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	18.3% 15/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Nervous system disorders Dizziness	14.7% 24/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	24.3% 42/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	15.9% 13/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Nervous system disorders Headache	12.9% 21/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	13.9% 24/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	12.2% 10/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Cardiac disorders Bradycardia	9.2% 15/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	9.2% 16/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	7.3% 6/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Nervous system disorders Dysgeusia	9.2% 15/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	12.1% 21/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	3.7% 3/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Skin and subcutaneous tissue disorders Skin odour abnormal	8.0% 13/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	0.58% 1/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	1.2% 1/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Nervous system disorders Tremor	4.3% 7/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	6.9% 12/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	9.8% 8/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Gastrointestinal disorders Vomiting	4.3% 7/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	6.9% 12/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	4.9% 4/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Ear and labyrinth disorders Tinnitus	1.8% 3/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	3.5% 6/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	6.1% 5/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.
Investigations Gamma-glutamyltransferase increase	1.2% 2/163 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	2.9% 5/173 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.	7.3% 6/82 • 28 days. For each Preferred Term (PT), subjects are included only once, even if they experienced multiple events in that PT.

Additional Information

Tricia Mulford

Heron Therapeutics, Inc.

Phone: 760-622-3709

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place