Postoperative Pain
Conditions
Keywords
bunion, bunionectomy, bunion surgery, postoperative pain
Brief summary
This is a Phase 2, open-label, multi-cohort study to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of a single, individualized dose of HTX-011 administered into the surgical site as a monotherapy or with other medications to enhance analgesia in subjects undergoing unilateral simple bunionectomy.
Interventions
DRUGHTX-011
HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.
DEVICELuer Lock applicator
Applicator for instillation.
DEVICEVial access device
Device for withdrawal of drug product.
DRUGaprepitant
Aprepitant, three single doses of aprepitant will be administered orally.
Sponsors
Heron Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Is scheduled to undergo a primary unilateral, distal, first metatarsal bunionectomy with osteotomy and internal fixation under regional 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. For cohort 2, acceptable contraceptives excludes hormonal contraceptives.
Exclusion criteria
* Has had a contralateral foot bunionectomy in the past 3 months prior to the scheduled surgery. * Has a planned concurrent surgical procedure (eg, bilateral bunionectomy or collateral procedures on the surgical foot). * 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 at 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. * For Cohort 2 only, has been administered aprepitant or another NK1 receptor antagonist 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. * For Cohort 2 only, is receiving pimozide, a strong or moderate CYP3A4 inhibitor, or a strong CYP3A4 inducer. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 72 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), sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours | 72 hours | — |
| Percentage of Subjects Receiving no Opioid Rescue | 72 hours | — |
| Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 72 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 measured at rest. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1: HTX-011 HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation. | 30 |
| Treatment Group 2: HTX-011 + Aprepitant HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation; Aprepitant, three single doses of aprepitant will be administered orally. | 17 |
| Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation and a scheduled multimodal analgesic (MMA) regimen. | 31 |
| Total | 78 |
Baseline characteristics
| Characteristic | Treatment Group 1: HTX-011 | Treatment Group 2: HTX-011 + Aprepitant | Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 16 Participants | 29 Participants | 75 Participants |
| Age, Continuous | 47.3 years STANDARD_DEVIATION 11.58 | 43.7 years STANDARD_DEVIATION 14.73 | 49.1 years STANDARD_DEVIATION 12.66 | 47.2 years STANDARD_DEVIATION 12.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 12 Participants | 15 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 5 Participants | 16 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 4 Participants | 6 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 16 Participants | 27 Participants | 71 Participants |
| Region of Enrollment United States | 30 participants | 17 participants | 31 participants | 78 participants |
| Sex: Female, Male Female | 28 Participants | 13 Participants | 29 Participants | 70 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 17 | 0 / 31 |
| other Total, other adverse events | 13 / 30 | 13 / 17 | 16 / 31 |
| serious Total, serious adverse events | 0 / 30 | 1 / 17 | 0 / 31 |
Outcome results
Primary
Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores
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), sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing).
Time frame: 72 hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 278.36 pain intensity score*hr | Standard Deviation 151.085 |
| Treatment Group 2: HTX-011 + Aprepitant | Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 288.23 pain intensity score*hr | Standard Deviation 115.79 |
| Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen | Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 126.93 pain intensity score*hr | Standard Deviation 129.819 |
Secondary
Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores
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 measured at rest.
Time frame: 72 hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 251.92 pain intensity score*hr | Standard Deviation 127.319 |
| Treatment Group 2: HTX-011 + Aprepitant | Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 252.39 pain intensity score*hr | Standard Deviation 112.996 |
| Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen | Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 113.10 pain intensity score*hr | Standard Deviation 124.696 |
Secondary
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours
Time frame: 72 hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1: HTX-011 | Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours | 11.47 MME, morphine milligram equivalents | Standard Deviation 10.198 |
| Treatment Group 2: HTX-011 + Aprepitant | Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours | 21.88 MME, morphine milligram equivalents | Standard Deviation 13.305 |
| Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen | Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours | 1.61 MME, morphine milligram equivalents | Standard Deviation 3.449 |
Secondary
Percentage of Subjects Receiving no Opioid Rescue
Time frame: 72 hours
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1: HTX-011 | Percentage of Subjects Receiving no Opioid Rescue | 6 Participants |
| Treatment Group 2: HTX-011 + Aprepitant | Percentage of Subjects Receiving no Opioid Rescue | 0 Participants |
| Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen | Percentage of Subjects Receiving no Opioid Rescue | 24 Participants |
Secondary
Percentage of Subjects Receiving no Opioid Rescue
Only subjects in Cohort 3 received a scheduled, non-opioid MMA regimen following surgery.
Time frame: Day 7 and Day 28
Population: Safety Population, Cohort 3 only
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group 1: HTX-011 | Percentage of Subjects Receiving no Opioid Rescue | Day 7 | 24 Participants |
| Treatment Group 1: HTX-011 | Percentage of Subjects Receiving no Opioid Rescue | Day 28 | 24 Participants |