Phase 2B Upper Extremity Nerve Block Study

• Sponsor: Heron Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03011333
• Collaborator: (none)
• Enrollment: 243
• Locations: 2
• Arms: 7
• Actual Duration (Months): 14.1
• Patients Per Site: 121.5
• Patients Per Site Per Month: 8.6

Study Details

Study Description

Brief Summary

This is a Phase 2B, randomized, assessor-blind, active- and saline placebo-controlled, multicenter study in subjects undergoing augmentation mammoplasty to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 when administered via ultrasound-guided lateral and medial pectoral nerve block before surgery.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain	Drug: HTX-011; Drug: Bupivacaine HCl without epinephrine; Drug: Saline Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 243 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2B, Randomized, Controlled Study of HTX-011 Administered Via Pectoral Nerve Block in Subjects Undergoing Upper Extremity Surgery for Augmentation Mammoplasty
• Actual Study Start Date: Jan 14, 2017
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Mar 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: HTX-011 HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.
Experimental: Group 2: HTX-011 HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.
Experimental: Group 3: HTX-011 HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.
Experimental: Group 4: HTX-011 HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.
Experimental: Group 5: HTX-011 HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation.	Drug: HTX-011; HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.
Active Comparator: Group 6: Bupivacaine HCl Bupivacaine HCl without epinephrine, 50 mg via nerve block.	Drug: Bupivacaine HCl without epinephrine; Bupivacaine HCl without epinephrine, 50 mg via nerve block.
Placebo Comparator: Group 7: Saline Placebo Saline placebo via nerve block.	Drug: Saline Placebo; Saline placebo via nerve block.

Outcome Measures

Primary Outcome Measures

1. Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores [24 hours]

   Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded with activity (NRS-A), raising the hands above the head (with wrists above the crown of the head) for at least 5 seconds.

Secondary Outcome Measures

1. Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) [72 Hours]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Is scheduled to undergo primary bilateral submuscular augmentation mammoplasty with saline or silicone smooth implants with a volume of 300 to 500 cc, inclusive. Note: textured implants are not allowed.

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

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

Exclusion Criteria:

• Has a planned concurrent surgical procedure.

• Has a planned reconstructive procedure status post breast cancer therapy.

• 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 medication.

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

• Has taken NSAIDs within 10 days prior to 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 other than to treat an AE that occurs after signing the ICF or for pretreatment prior to a needle placement.

• Has initiated treatment with any of the following medications within 1 month prior to study drug administration or is taking any of these medications to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin, duloxetine, or cyclooxygenase-2 (COX-2) inhibitors. (Note: If a subject is taking one of these medications for a reason other than pain control, she must be on a stable scheduled dose [ie, not "as needed"] for at least 1 month prior to study drug administration.) Anxiolytics prior to surgery are permitted, if necessary.

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

• Has a known history of Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV).

• Has uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments

• Has any chronic neuromuscular deficit of either pectoral nerve function or arm/shoulder/truncal musculature.

• Has any chronic condition or disease that would compromise neurological or vascular assessments.

• Had a malignancy in the last year, with the exception of non-metastatic 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. Subjects taking medical marijuana are not allowed to participate in the 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 in 12 months.

• Has a body mass index (BMI) >35 kg/m2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Pasadena	California	United States	91105
2		Houston	Texas	United States	77027

Sponsors and Collaborators

• Heron Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 15, 2017
• Statistical Analysis Plan - Jan 4, 2018

More Information

Publications

None provided.

• Responsible Party: Heron Therapeutics
• ClinicalTrials.gov Identifier: NCT03011333
• Other Study ID Numbers: HTX-011-211
• First Posted: Jan 5, 2017
• Last Update Posted: Oct 29, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Pain, Postoperative; Epinephrine; Bupivacaine

Study Results

Participant Flow

Pre-assignment Detail	A total of 243 subjects received study drug.

Arm/Group Title	Group 1: HTX-011	Group 2: HTX-011	Group 3: HTX-011	Group 4: HTX-011	Group 5: HTX-011	Group 6: Bupivacaine HCl	Group 7: Saline Placebo
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block	HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block	HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation	Bupivacaine HCl without epinephrine, 50 mg via nerve block	Saline placebo via nerve block
Period Title: Overall Study
STARTED	12	27	25	47	50	41	41
COMPLETED	12	26	25	46	46	37	36
NOT COMPLETED	0	1	0	1	4	4	5

Baseline Characteristics

Arm/Group Title	Group 1: HTX-011	Group 2: HTX-011	Group 3: HTX-011	Group 4: HTX-011	Group 5: HTX-011	Group 6: Bupivacaine HCl	Group 7: Saline Placebo	Total
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block	HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block	HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation	Bupivacaine HCl without epinephrine, 50 mg via nerve block	Saline placebo via nerve block	Total of all reporting groups
Overall Participants	12	27	25	47	50	41	41	243
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	27 100%	25 100%	47 100%	50 100%	41 100%	41 100%	243 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.4 (6.56)	32.1 (8.51)	30.5 (5.64)	30.9 (8.08)	32.0 (8.64)	30.4 (7.75)	31.3 (9.03)	31.2 (8.01)
Sex: Female, Male (Count of Participants)
Female	12 100%	27 100%	25 100%	47 100%	50 100%	41 100%	41 100%	243 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 50%	10 37%	10 40%	18 38.3%	17 34%	17 41.5%	16 39%	94 38.7%
Not Hispanic or Latino	6 50%	17 63%	15 60%	29 61.7%	33 66%	24 58.5%	25 61%	149 61.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 3.7%	1 4%	3 6.4%	2 4%	2 4.9%	2 4.9%	11 4.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 16.7%	4 14.8%	3 12%	6 12.8%	11 22%	3 7.3%	7 17.1%	36 14.8%
White	10 83.3%	22 81.5%	20 80%	38 80.9%	37 74%	35 85.4%	32 78%	194 79.8%
More than one race	0 0%	0 0%	1 4%	0 0%	0 0%	1 2.4%	0 0%	2 0.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	27 100%	25 100%	47 100%	50 100%	41 100%	41 100%	243 100%

Outcome Measures

1. Primary Outcome

Title	Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores
Description	Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded with activity (NRS-A), raising the hands above the head (with wrists above the crown of the head) for at least 5 seconds.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Group 1: HTX-011	Group 2: HTX-011	Group 3: HTX-011	Group 4: HTX-011	Group 5: HTX-011	Group 6: Bupivacaine HCl	Group 7: Saline Placebo
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block	HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block	HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation	Bupivacaine HCl without epinephrine, 50 mg via nerve block	Saline placebo via nerve block
Measure Participants	12	27	25	12	50	41	41
Mean (Standard Deviation) [pain intensity score*hr]	124.51 (59.462)	136.17 (58.598)	136.76 (56.034)	116.71 (52.622)	114.87 (48.214)	133.83 (49.493)	151.52 (46.213)

2. Secondary Outcome

Title	Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)
Time Frame	72 Hours

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Group 1: HTX-011	Group 2: HTX-011	Group 3: HTX-011	Group 4: HTX-011	Group 5: HTX-011	Group 6: Bupivacaine HCl	Group 7: Saline Placebo
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block	HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block	HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block	HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation	Bupivacaine HCl without epinephrine, 50 mg via nerve block	Saline placebo via nerve block
Measure Participants	12	27	25	47	50	41	41
Mean (Standard Deviation) [Morphine milligram equivalents (MME)]	38.71 (28.650)	24.39 (19.878)	38.00 (19.452)	28.84 (22.603)	37.46 (21.452)	33.57 (23.088)	36.38 (23.275)

Adverse Events

Time Frame	28 Days.
Adverse Event Reporting Description	Subjects reporting more than one Treatment Emergent Adverse Event (TEAE) are counted only once.
Arm/Group Title	Group 1: HTX-011		Group 2: HTX-011		Group 3: HTX-011		Group 4: HTX-011		Group 5: HTX-011		Group 6: Bupivacaine HCl		Group 7: Saline Placebo
Arm/Group Description	HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block		HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block		HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block		HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block		HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation		Bupivacaine HCl without epinephrine, 50 mg via nerve block		Saline placebo via nerve block
All Cause Mortality
	Group 1: HTX-011		Group 2: HTX-011		Group 3: HTX-011		Group 4: HTX-011		Group 5: HTX-011		Group 6: Bupivacaine HCl		Group 7: Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/27 (0%)		0/25 (0%)		0/47 (0%)		0/50 (0%)		0/41 (0%)		0/41 (0%)
Serious Adverse Events
	Group 1: HTX-011		Group 2: HTX-011		Group 3: HTX-011		Group 4: HTX-011		Group 5: HTX-011		Group 6: Bupivacaine HCl		Group 7: Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/27 (0%)		1/25 (4%)		0/47 (0%)		1/50 (2%)		2/41 (4.9%)		0/41 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/12 (0%)		0/27 (0%)		1/25 (4%)		0/47 (0%)		0/50 (0%)		0/41 (0%)		0/41 (0%)
Product Issues
Device breakage	0/12 (0%)		0/27 (0%)		0/25 (0%)		0/47 (0%)		1/50 (2%)		0/41 (0%)		0/41 (0%)
Reproductive system and breast disorders
Breast haematoma	0/12 (0%)		0/27 (0%)		0/25 (0%)		0/47 (0%)		0/50 (0%)		2/41 (4.9%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Group 1: HTX-011		Group 2: HTX-011		Group 3: HTX-011		Group 4: HTX-011		Group 5: HTX-011		Group 6: Bupivacaine HCl		Group 7: Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		21/27 (77.8%)		23/25 (92%)		43/47 (91.5%)		47/50 (94%)		33/41 (80.5%)		35/41 (85.4%)
Cardiac disorders
Tachycardia	0/12 (0%)		0/27 (0%)		1/25 (4%)		5/47 (10.6%)		6/50 (12%)		2/41 (4.9%)		2/41 (4.9%)
Bradycardia	1/12 (8.3%)		0/27 (0%)		0/25 (0%)		2/47 (4.3%)		2/50 (4%)		1/41 (2.4%)		1/41 (2.4%)
Gastrointestinal disorders
Nausea	8/12 (66.7%)		15/27 (55.6%)		14/25 (56%)		37/47 (78.7%)		37/50 (74%)		25/41 (61%)		26/41 (63.4%)
Vomiting	4/12 (33.3%)		6/27 (22.2%)		7/25 (28%)		17/47 (36.2%)		19/50 (38%)		14/41 (34.1%)		16/41 (39%)
Constipation	2/12 (16.7%)		4/27 (14.8%)		2/25 (8%)		7/47 (14.9%)		7/50 (14%)		6/41 (14.6%)		8/41 (19.5%)
Paraesthesia oral	0/12 (0%)		0/27 (0%)		2/25 (8%)		0/47 (0%)		0/50 (0%)		0/41 (0%)		2/41 (4.9%)
General disorders
Medical device site reaction	0/12 (0%)		1/27 (3.7%)		3/25 (12%)		4/47 (8.5%)		5/50 (10%)		2/41 (4.9%)		4/41 (9.8%)
Pyrexia	0/12 (0%)		0/27 (0%)		0/25 (0%)		1/47 (2.1%)		6/50 (12%)		0/41 (0%)		0/41 (0%)
Catheter site inflammation	0/12 (0%)		2/27 (7.4%)		0/25 (0%)		0/47 (0%)		0/50 (0%)		1/41 (2.4%)		0/41 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/12 (0%)		1/27 (3.7%)		1/25 (4%)		5/47 (10.6%)		3/50 (6%)		2/41 (4.9%)		3/41 (7.3%)
Muscle twitching	0/12 (0%)		0/27 (0%)		4/25 (16%)		2/47 (4.3%)		0/50 (0%)		2/41 (4.9%)		0/41 (0%)
Pain in extremity	0/12 (0%)		2/27 (7.4%)		1/25 (4%)		1/47 (2.1%)		0/50 (0%)		0/41 (0%)		0/41 (0%)
Nervous system disorders
Dizziness	1/12 (8.3%)		6/27 (22.2%)		10/25 (40%)		4/47 (8.5%)		6/50 (12%)		8/41 (19.5%)		4/41 (9.8%)
Headache	0/12 (0%)		4/27 (14.8%)		4/25 (16%)		3/47 (6.4%)		7/50 (14%)		4/41 (9.8%)		5/41 (12.2%)
Dysgeusia	0/12 (0%)		0/27 (0%)		5/25 (20%)		5/47 (10.6%)		2/50 (4%)		1/41 (2.4%)		2/41 (4.9%)
Hypoaesthesia	1/12 (8.3%)		0/27 (0%)		1/25 (4%)		1/47 (2.1%)		1/50 (2%)		0/41 (0%)		2/41 (4.9%)
Tremor	0/12 (0%)		0/27 (0%)		2/25 (8%)		1/47 (2.1%)		1/50 (2%)		1/41 (2.4%)		2/41 (4.9%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/12 (8.3%)		1/27 (3.7%)		0/25 (0%)		1/47 (2.1%)		1/50 (2%)		1/41 (2.4%)		0/41 (0%)
Skin and subcutaneous tissue disorders
Pruritus	4/12 (33.3%)		1/27 (3.7%)		4/25 (16%)		2/47 (4.3%)		4/50 (8%)		7/41 (17.1%)		5/41 (12.2%)
Pruritus generalised	1/12 (8.3%)		6/27 (22.2%)		1/25 (4%)		3/47 (6.4%)		1/50 (2%)		1/41 (2.4%)		1/41 (2.4%)
Rash	0/12 (0%)		3/27 (11.1%)		2/25 (8%)		2/47 (4.3%)		4/50 (8%)		4/41 (9.8%)		1/41 (2.4%)
Hyperhidrosis	0/12 (0%)		4/27 (14.8%)		0/25 (0%)		0/47 (0%)		4/50 (8%)		3/41 (7.3%)		1/41 (2.4%)
Vascular disorders
Hypotension	1/12 (8.3%)		0/27 (0%)		0/25 (0%)		6/47 (12.8%)		6/50 (12%)		1/41 (2.4%)		1/41 (2.4%)

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.