Phase 2 Herniorrhaphy Study for Opioid Elimination

• Sponsor: Heron Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03695367
• Collaborator: (none)
• Enrollment: 63
• Locations: 5
• Arms: 2
• Actual Duration (Months): 2.5
• Patients Per Site: 12.6
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

This is a Phase 2, open-label study in subjects undergoing unilateral open inguinal herniorrhaphy.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain	Drug: HTX-011; Device: Luer lock applicator; Device: Vial access device; Drug: Ibuprofen; Drug: Acetaminophen; Drug: Ketorolac	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 2, Open-Label Study of HTX 011 in a Multimodal Analgesic Regimen for Decreased Opioid Use Following Unilateral Open Inguinal Herniorrhaphy
• Actual Study Start Date: Oct 1, 2018
• Actual Primary Completion Date: Nov 20, 2018
• Actual Study Completion Date: Dec 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: HTX-011 + MMA Regimen HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), 300 mg/ 9 mg via instillation.; Device: Luer lock applicator; Applicator for instillation.; Device: Vial access device; Device for withdrawal of drug product.; Drug: Ibuprofen; Ibuprofen, 600 mg.; Drug: Acetaminophen; Acetaminophen, 1 g.
Experimental: Cohort 2: HTX-011 + MMA Regimen + Ketorolac HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), 300 mg/ 9 mg via instillation.; Device: Luer lock applicator; Applicator for instillation.; Device: Vial access device; Device for withdrawal of drug product.; Drug: Ibuprofen; Ibuprofen, 600 mg.; Drug: Acetaminophen; Acetaminophen, 1 g.; Drug: Ketorolac; Intraoperative IV ketorolac.

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Receiving no Opioid Rescue [72 hours]

Secondary Outcome Measures

1. Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [IV MME]) [72 hours]

2. Percentge of Subjects Receiving no Opioid Rescue [0-24 hours, 24-48 hours, 24-72 hours, 48-72 hours]

3. Percentge of Subjects Receiving no Opioid Rescue [Day 28]

4. Percentge of Subjects in Severe Pain With Numeric Rating Scale (NRS-R; Windowed Worst Observation Carried Forward) of Pain Intensity Scores >7 on a Scale of 0-10 at Any Point. NRS-R for Pain Where 0 Equals no Pain and 10 Equals Worst Pain Imaginable. [72 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Is scheduled to undergo a unilateral open inguinal herniorrhaphy with mesh under general anesthesia.

• Has an American Society of Anesthesiologists Physical Status of I, II, or III.

• Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives.

Exclusion Criteria:

• Had any prior inguinal hernia repair except as a child (less than 6 years of age).

• Has a planned concurrent surgical procedure (eg, bilateral herniorrhaphy).

• Has a pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.

• Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.

• Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.

• Has taken any NSAIDs within least 10 days prior to the scheduled surgery.

• Has taken long-acting opioids within 3 days prior to the scheduled surgery.

• Has taken any opioids within 24 hours prior to the scheduled surgery.

• Has been administered bupivacaine within 5 days prior to the scheduled surgery.

• Has been administered any local anesthetic within 72 hours prior to the scheduled surgery.

• Has initiated treatment with study medications within 1 month prior to study drug administration that can impact pain control.

• Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug.

• Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments.

• As per subject history and/or medical records, has active infection or is currently undergoing treatment for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV).

• Has uncontrolled anxiety, psychiatric, or neurological disorder.

• Had a malignancy in the last year, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.

• Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. Note: Subjects with a positive drug screen who are taking an allowed, prescribed medication that is known to result in a positive drug test (eg, amphetamine and dextroamphetamine for attention-deficit/hyperactivity disorder, benzodiazepine for anxiety disorder) may be eligible for participation in the study at the discretion of the Sponsor. Subjects taking any marijuana (medical or recreational) are not allowed to participate in the study.

• Previously participated in an HTX-011 study.

• Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half-lives.

• Has undergone 3 or more surgeries within 12 months.

• Has a body mass index (BMI) >39 kg/m2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801
2	Lotus Clinical Research, LLC	Pasadena	California	United States	91105
3	JBR Clinical Research	Draper	Utah	United States	84020
4	JBR Clinical Research	Murray	Utah	United States	84107
5	JBR Clinical Research	Salt Lake City	Utah	United States	84124

Sponsors and Collaborators

• Heron Therapeutics

Investigators

• Study Chair: Neil Singla, MD, Lotus Clinical Research, LLC

Study Documents (Full-Text)

• Study Protocol - Aug 31, 2018
• Statistical Analysis Plan - Oct 18, 2018

More Information

Publications

None provided.

• Responsible Party: Heron Therapeutics
• ClinicalTrials.gov Identifier: NCT03695367
• Other Study ID Numbers: HTX-011-215
• First Posted: Oct 4, 2018
• Last Update Posted: Oct 25, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Heron Therapeutics: inguinal hernia; hernia; hernia surgery; postoperative pain; herniorrhaphy
• Additional relevant MeSH terms: Pain, Postoperative; Acetaminophen; Ibuprofen; Ketorolac

Study Results

Participant Flow

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
Period Title: Overall Study
STARTED	33	30
COMPLETED	32	26
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac	Total
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.	Total of all reporting groups
Overall Participants	33	30	63
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	30 90.9%	26 86.7%	56 88.9%
>=65 years	3 9.1%	4 13.3%	7 11.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.9 (13.52)	46.1 (14.99)	48.7 (14.33)
Sex: Female, Male (Count of Participants)
Female	0 0%	4 13.3%	4 6.3%
Male	33 100%	26 86.7%	59 93.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 42.4%	9 30%	23 36.5%
Not Hispanic or Latino	19 57.6%	21 70%	40 63.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3%	0 0%	1 1.6%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 3%	0 0%	1 1.6%
Black or African American	1 3%	4 13.3%	5 7.9%
White	30 90.9%	26 86.7%	56 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	33 100%	30 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Receiving no Opioid Rescue
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
Measure Participants	33	30
Count of Participants [Participants]	30 90.9%	27 90%

2. Secondary Outcome

Title	Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [IV MME])
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
Measure Participants	33	30
Mean (Standard Deviation) [MME, morphine milligram equivalents]	0.59 (2.141)	1.32 (4.199)

3. Secondary Outcome

Title	Percentge of Subjects Receiving no Opioid Rescue
Time Frame	0-24 hours, 24-48 hours, 24-72 hours, 48-72 hours

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
Measure Participants	33	30
0-24 hours	30 90.9%	27 90%
24-48 hours	32 97%	29 96.7%
24-72 hours	32 97%	28 93.3%
48-72 hours	33 100%	28 93.3%

4. Secondary Outcome

Title	Percentge of Subjects Receiving no Opioid Rescue
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
Measure Participants	33	30
Count of Participants [Participants]	28 84.8%	24 80%

5. Secondary Outcome

Title	Percentge of Subjects in Severe Pain With Numeric Rating Scale (NRS-R; Windowed Worst Observation Carried Forward) of Pain Intensity Scores >7 on a Scale of 0-10 at Any Point. NRS-R for Pain Where 0 Equals no Pain and 10 Equals Worst Pain Imaginable.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen	Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
Measure Participants	33	30
Count of Participants [Participants]	5 15.2%	6 20%

Adverse Events

Time Frame	28 Days.
Adverse Event Reporting Description	At each level of summarization (any event, System Organ Class, and Preferred Term), subjects reporting more than one TEAE are counted only once.
Arm/Group Title	Cohort 1: HTX-011 + MMA Regimen		Cohort 2: HTX-011 + MMA Regimen + Ketorolac
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen.		HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg via instillation; non-opioid multimodal analgesic (MMA) regimen and IV ketorolac.
All Cause Mortality
	Cohort 1: HTX-011 + MMA Regimen		Cohort 2: HTX-011 + MMA Regimen + Ketorolac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/30 (0%)
Serious Adverse Events
	Cohort 1: HTX-011 + MMA Regimen		Cohort 2: HTX-011 + MMA Regimen + Ketorolac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: HTX-011 + MMA Regimen		Cohort 2: HTX-011 + MMA Regimen + Ketorolac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/33 (15.2%)		7/30 (23.3%)
Gastrointestinal disorders
Nausea	2/33 (6.1%)		3/30 (10%)
Vomiting	0/33 (0%)		2/30 (6.7%)
Nervous system disorders
Headache	1/33 (3%)		2/30 (6.7%)
Dizziness	0/33 (0%)		2/30 (6.7%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/33 (9.1%)		2/30 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.