Postoperative Pain
Conditions
Keywords
inguinal hernia, hernia, hernia surgery, postoperative pain, herniorrhaphy
Brief summary
This is a Phase 3, randomized, double-blind, saline placebo- and active-controlled, multicenter study to evaluate the analgesic efficacy and safety of HTX 011 administered via local administration into the surgical site in subjects undergoing unilateral open inguinal herniorrhaphy.
Interventions
DRUGHTX-011
HTX 011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation
DRUGBupivacaine HCl
Bupivacaine HCl without epinephrine, 75 mg by injection
DRUGSaline placebo
Saline placebo by instillation
DEVICELuer-lock applicator
Applicator for instillation
DEVICEVial access device
Device for withdrawal of drug product
Sponsors
Heron Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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. * 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. * 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. * 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 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. * 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. * Has a known history of Hepatitis B, human immunodeficiency virus (HIV), or active Hepatitis C. * Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, might interfere with study 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 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) 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 within 12 months. * Has a body mass index (BMI) \>39 kg/m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 72 hours | 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. |
| Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo. | 72 hours | — |
| Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl. | 72 hours | — |
| Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl. | 72 hours | — |
Countries
Belgium, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1: HTX-011 HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg by instillation. | 164 |
| Treatment Group 2: Bupivacaine HCI Bupivacaine HCl without epinephrine, 75 mg by injection. | 172 |
| Treatment Group 3: Saline Placebo Saline Placebo by instillation. | 82 |
| Total | 418 |
Baseline characteristics
| Characteristic | Total | Treatment Group 1: HTX-011 | Treatment Group 2: Bupivacaine HCI | Treatment Group 3: Saline Placebo |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 15 Participants | 11 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 387 Participants | 149 Participants | 161 Participants | 77 Participants |
| Age, Continuous | 48.9 years STANDARD_DEVIATION 12.75 | 48.9 years STANDARD_DEVIATION 13.29 | 49.4 years STANDARD_DEVIATION 11.26 | 48.0 years STANDARD_DEVIATION 14.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 124 Participants | 43 Participants | 51 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 294 Participants | 121 Participants | 121 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 17 Participants | 16 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 370 Participants | 139 Participants | 153 Participants | 78 Participants |
| Region of Enrollment Belgium | 4 participants | 4 participants | 0 participants | 0 participants |
| Region of Enrollment United States | 414 participants | 160 participants | 172 participants | 82 participants |
| Sex: Female, Male Female | 23 Participants | 12 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 395 Participants | 152 Participants | 164 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 0 / 173 | 0 / 82 |
| other Total, other adverse events | 84 / 163 | 104 / 173 | 49 / 82 |
| serious Total, serious adverse events | 2 / 163 | 1 / 173 | 1 / 82 |
Outcome results
Primary
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.
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.
Time frame: 72 hours
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | 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. | 269.39 pain intensity score*hr | Standard Deviation 173.719 |
| Treatment Group 3: Saline Placebo | 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 |
p-value: =0.000495% CI: [-125.83, -37.02]ANOVA
Secondary
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.
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.
Time frame: 72 hours
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | 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. | 269.39 pain intensity score*hr | Standard Deviation 173.719 |
| Treatment Group 3: Saline Placebo | 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 |
p-value: <0.000195% CI: [-108.32, -36.65]ANOVA
Secondary
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.
Time frame: 72 hours
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl. | 10.85 IV milligram morphine equivalent (MME) | Standard Deviation 17.062 |
| Treatment Group 3: Saline Placebo | 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 |
p-value: =0.024Wilcoxon (Mann-Whitney)
Secondary
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.
Time frame: 72 hours
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo. | 10.85 IV milligram morphine equivalent (MME) | Standard Deviation 17.062 |
| Treatment Group 3: Saline Placebo | 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 |
p-value: =0.0001Wilcoxon (Mann-Whitney)
Secondary
Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.
Time frame: 72 hours
Population: ITT Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1: HTX-011 | Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl. | 84 Participants |
| Treatment Group 3: Saline Placebo | Percetange of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl. | 69 Participants |
p-value: =0.048695% CI: [0.003, 0.218]Fisher Exact