Total Knee Arthroplasty (TKA) Study of HTX-011 in an Mult... | NCT03974932

Label	Type	Description	Intervention Names
Cohort 1	Experimental	HTX-011 + MMA	Drug: HTX-011 Drug: Ibuprofen Drug: Acetaminophen Drug: Celecoxib Device: Luer Lock Applicator
Cohort 2	Experimental	HTX-011 + MMA	Drug: HTX-011 Drug: Ibuprofen Drug: Acetaminophen Drug: Celecoxib Device: Luer Lock Applicator
Cohort 3	Experimental	HTX-011 + MMA	Drug: Ibuprofen Drug: Acetaminophen Drug: Celecoxib Drug: +/- Bupivacaine HCl Device: Luer Lock Applicator Drug: HTX-011
Cohort 4	Experimental	HTX-011 + MMA	Drug: HTX-011 Drug: Ibuprofen Drug: Acetaminophen Device: Luer Lock Applicator

Name	Type	Description	Arm Group Labels	Other Names
HTX-011	Drug	Dual-acting local anesthetic. Dose 1.	Cohort 1 Cohort 2 Cohort 4

Measure	Description	Time Frame
Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS).	The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.	12 through 48 hours

Measure	Description	Time Frame
Mean AUC of VAS Scores.	The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.	72 hours
Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is scheduled to undergo primary unilateral TKA under spinal anesthesia.
Has not previously undergone TKA in either knee.
Has an American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
Is able to walk at least 20 feet with optional use of a 4-legged walker for balance.
Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or is at least 2 years post-menopausal; or is in a monogamous relationship with a partner who is surgically sterile; or using acceptable contraceptives.

Exclusion Criteria:

Has a planned concurrent surgical procedure.
Has other 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.
Using or expected to use Factor IX Complex or anti-inhibitor coagulant concentrates during the study.
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 the scheduled surgery with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting).
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 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.
Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
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.
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.
Is currently undergoing treatment for hepatitis B, hepatitis C, or HIV.
Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, might interfere with study assessments.
Has acquired defective color vision or acute gastrointestinal ulcers, either of which could interfere with scheduled study medications.
Has any chronic neuromuscular deficit of either femoral nerve function or thigh 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 nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
Has undergone 3 or more surgeries within 12 months.
Has a body mass index (BMI) >39 kg/m2.

Facility	Status	City	State	ZIP	Country	Contacts
Helen Keller Hospital		Sheffield	Alabama	35660	United States
Phoenix Clinical Research, LLC

ID	Title	Description
FG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
FG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 2, 2020	Dec 17, 2021

ID	Title	Description
BG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
BG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
BG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
BG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00066 BG00114 BG00216 BG00320 BG004116

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS).

The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.

Posted

Mean

Standard Deviation

pain intensity score*hr

12 through 48 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants	OG00066 OG00114 OG00216 OG003

Title

Denominators

Categories

Title	Measurements
	OG000155.57± 95.651 OG001185.27± 86.898 OG002161.36± 86.627 OG003

Secondary

Mean AUC of VAS Scores.

Posted

Mean

Standard Deviation

pain intensity score*hr

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Secondary

Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).

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". NRS scores are measured at rest.

Posted

Mean

Standard Deviation

pain intensity score*hr

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Secondary

Percentage of Subjects With Severe Pain.

Severe Pain defined as a VAS score ≥7.5 cm.

Posted

Count of Participants

Participants

24 hours, 48 hours, 72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts

Secondary

Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]).

Posted

Mean

Standard Deviation

MME, morphine milligram equivalency

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Who Are Opioid-free

Posted

Number

participants

72 Hours to Day 11

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11.

Posted

Count of Participants

Participants

72 hours through Day 11

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Median Time to First Opioid Rescue Medication.

Posted

Median

95% Confidence Interval

Hours

Through 72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge.

Posted

Count of Participants

Participants

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit.

Posted

Count of Participants

Participants

72 hours through Day 11

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Achieving a Score of "Good" or Better (>1) Pain Control Based on Patient Global Assessment (PGA).

Patient's Global Assessment (PGA) of pain control is a 4-point scale in which subjects rate how well their pain has been controlled (0 = Poor; 1 = Fair; 2 = Good; 3 = Excellent).

Posted

Count of Participants

Participants

24 hours, 48 hours, 72 hours, Day 11

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Secondary

Median Time to First Ambulation Postsurgery.

Posted

Median

95% Confidence Interval

Hours

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain.

Posted

Count of Participants

Participants

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Percentage of Subjects Who First Achieve an MPADSS Score ≥9.

Subjects were assessed for readiness for discharge using the Modified Post-Anesthesia Discharge Scoring System (MPADSS) that assesses 5 clinical variables: vital signs, ambulation, nausea/vomiting, pain, and surgical bleeding, each on a 3-point scale of 0, 1, or 2 with 0 being the worst score and 2 being the best score. Subjects with an MPADSS score of 9 or 10 were considered ready for discharge.

Posted

Count of Participants

Participants

2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4

Secondary

Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility.

Number Analyzed represents Subjects who were discharged home.

Posted

Count of Participants

Participants

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts

Secondary

Mean Overall Benefit of Analgesia Score (OBAS).

Subjects were questioned about their overall benefit of analgesia. Overall benefit of analgesia score (OBAS) assesses current pain at rest, vomiting, itching, sweating, freezing, dizziness, and overall satisfaction with postoperative pain during the previous 24 hours. To calculate the OBAS score, each of the subscale scores (0=minimum; 4=maximum) are summed for a combined OBAS score. Possible scores could range from 0 to 28 with a lower score indicating greater benefit.

Posted

Mean

Standard Deviation

Scores on a scale

24 hours, 48 hours, 72 hours, Day 11

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4

Secondary

Mean Total TSQM-9 Score

The Treatment Satisfaction Questionnaire for Medication (TSQM-9) contains 9 items assessing Effectiveness, Convenience, and Global Satisfaction domains. Responses to items are rated on a 5-point or 7-point rating scale. Scores for each domain are computed by adding the TSQM items in each domain and then transforming the values in to a composite score ranging from 0 to 100, with higher scores representing higher satisfaction.

Posted

Mean

Standard Deviation

Scores on a scale

72 hours through Day 11

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Secondary

Maximum Concentration (Cmax)

Posted

Mean

Standard Deviation

ng/mL

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Secondary

Time of Occurrence of Maximum Concentration (Tmax)

Posted

Median

Full Range

hours

72 hours

ID	Title	Description
OG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.
OG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.
OG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.
OG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dizziness	Nervous system disorders	MedDRA version 22.0	Systematic Assessment	EG0009 affected66 at risk EG0011 affected14 at risk EG0022 affected16 at risk EG0031 affected20 at risk
Headache	Nervous system disorders	MedDRA version 22.0	Systematic Assessment	EG0002 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Sciatica	Nervous system disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Vision blurred	Eye disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected14 at risk EG0022 affected16 at risk EG003
Bradycardia	Cardiac disorders	MedDRA version 22.0	Systematic Assessment	EG0003 affected66 at risk EG0013 affected14 at risk EG0022 affected16 at risk EG003
Tachycardia	Cardiac disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Hypertension	Vascular disorders	MedDRA version 22.0	Systematic Assessment	EG0003 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Hypotension	Vascular disorders	MedDRA version 22.0	Systematic Assessment	EG0002 affected66 at risk EG0011 affected14 at risk EG0021 affected16 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG00033 affected66 at risk EG0016 affected14 at risk EG00211 affected16 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG00017 affected66 at risk EG0013 affected14 at risk EG0027 affected16 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG00010 affected66 at risk EG0013 affected14 at risk EG0026 affected16 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0021 affected16 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 22.0	Systematic Assessment	EG0005 affected66 at risk EG0010 affected14 at risk EG0022 affected16 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0021 affected16 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA version 22.0	Systematic Assessment	EG0003 affected66 at risk EG0013 affected14 at risk EG0020 affected16 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Oedema peripheral	General disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0013 affected14 at risk EG0021 affected16 at risk EG003
Peripheral swelling	General disorders	MedDRA version 22.0	Systematic Assessment	EG0003 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Chest pain	General disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Asthenia	General disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Blood pressure increased	Investigations	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Blood pressure decreased	Investigations	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0009 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0023 affected16 at risk EG003
Incision site erythema	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0012 affected14 at risk EG0020 affected16 at risk EG003
Incision site haemorrhage	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0021 affected16 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Incision site oedema	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Incision site pruritus	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Postoperative hypertension	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Wound secretion	Injury, poisoning and procedural complications	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA version 22.0	Systematic Assessment	EG0004 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA version 22.0	Systematic Assessment	EG0003 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 22.0	Systematic Assessment	EG0003 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 22.0	Systematic Assessment	EG0001 affected66 at risk EG0010 affected14 at risk EG0021 affected16 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0011 affected14 at risk EG0020 affected16 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA version 22.0	Systematic Assessment	EG0000 affected66 at risk EG0010 affected14 at risk EG0020 affected16 at risk EG003

ID	Term
D000377	Agnosia
D010149	Pain, Postoperative

ID	Term
D010468	Perceptual Disorders
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D011183	Postoperative Complications
D010335	Pathologic Processes
D010146	Pain

ID	Term
D010666	Phenylpropionates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D000814	Aniline Compounds
D000588	Amines
D000096926	Benzenesulfonamides
D013449	Sulfonamides
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D013450	Sulfones
D013457	Sulfur Compounds
D011720	Pyrazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1 and Cohort 2 (Pooled)	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen.	66	2	66	56	66
EG001	Cohort 3: Group A	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen.	14	0	14	12	14
EG002	Cohort 3: Group B	HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen.	16	0	16	14	16
EG003	Cohort 4	HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen.	20	2	20	15	20

ID	Term
D007052	Ibuprofen
D000082	Acetaminophen
D000068579	Celecoxib
D002045	Bupivacaine