Postoperative PainPhase 4AMAZENCT06109428
Cohort 2 (Abdominoplasty) of: A Multi-surgery Assessment of ZYNRELEF (HTX-011)
A Phase 4 study testing MMA regimen, ZYNRELEF kit components for administration and HTX-011 in people with Postoperative Pain and Abdominoplasty Surgery, run by Heron Therapeutics at 2 sites in United States.
Trial summary
Cohort 2 (subjects undergoing abdominoplasty) of a Phase 4, randomized, blinded, active-controlled, multicohort study to evaluate HTX-011 compared with bupivacaine HCl in subjects undergoing different surgical procedures See also the separate record for the master study protocol (NCT05109312). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Pain, Abdominoplasty Surgery, Multimodal Analgesia
- What is being tested?
- MMA regimen, ZYNRELEF kit components for administration and HTX-011
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Oct 2021to 7 Apr 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
- Is scheduled to undergo abdominoplasty.
Who cannot join
- Is undergoing a revision surgery.
- Has a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to bupivacaine (or other local anesthetics), NSAIDs, acetaminophen, oxycodone, morphine, or hydromorphone.
- History of severe allergic reaction to aspirin or other NSAIDs, or known history of severe gastrointestinal adverse reactions associated with NSAID use.
- Has taken meloxicam within 10 days prior to the scheduled surgery, or any NSAID within 24 hours prior to the scheduled surgery, with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
- Opioid use for most days within the last 3 months prior to Screening in the opinion of the Investigator.
- Has been administered immediate-release bupivacaine HCl within 5 days prior to the scheduled surgery, or a modified-release bupivacaine product within 14 days prior to the scheduled surgery.
Show all 14Show fewer
- Has initiated treatment with any of the following medications within 1 month prior to study drug administration: selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, gabapentin, pregabalin, duloxetine, or cyclooxygenase-2 inhibitors.
- Has been administered systemic steroids within 5 half-lives or 10 days prior to the scheduled surgery (whichever is longer).
- Has a known or suspected history of drug abuse, a positive drug screen (except for cannabinoids) on the day of surgery, or a history of alcohol abuse within the past 5 years.
- Suspected or confirmed active coronavirus disease 2019 (COVID-19) infection.
- 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, other than for diagnostic procedures (eg, colonoscopy).
- Has a body mass index (BMI) >40 kg/m2.
- Had undergone prior abdominoplasty or major abdominal wall surgery.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
First Surgical Hospital
Bellaire, Texas, 77401
Endeavor Clinical Trials, LLC
San Antonio, Texas, 78229
About this study
Official title: A Phase 4, Randomized, Blinded, Active-Controlled Study of HTX-011 in Subjects Undergoing Different Surgical Procedures, Cohort 2: Abdominoplasty
Cohort 2 (subjects undergoing abdominoplasty) of a Phase 4, randomized, blinded, active-controlled, multicohort study to evaluate HTX-011 compared with bupivacaine HCl in subjects undergoing different surgical procedures
See also the separate record for the master study protocol (NCT05109312).
Read the detailed description
Subjects were randomized in a 2:1 ratio to have either HTX-011 400 mg/12 mg or bupivacaine HCl 125 mg administered into the surgical site prior to closure. Subjects and study site personnel performing postoperative safety and pharmacodynamic (PD) assessments were blinded to treatment assignments; however, unblinded study site staff were permitted to collect samples for pharmacokinetic (PK) analysis.
During surgery (on Study Day 1), in addition to study drug (HTX-011 or bupivacaine HCl), subjects could receive intravenous (IV) fentanyl, and all subjects were to receive a single dose of either IV morphine or IV hydromorphone just prior to the application of dermal sutures.
Subjects remained in the facility through 72 hours post-dose for safety, PK, and PD assessments. Subjects received a scheduled non-opioid multimodal analgesic (MMA) regimen throughout the 72-hour postoperative period consisting of oral (PO) acetaminophen 1 g every 8 hours (q8h) alternating with PO ibuprofen 400 mg q8h.
After discharge (Day 4), subjects were to continue their scheduled multimodal analgesic (MMA) regimen through Day 7, while awake, and complete the daily diary to record opioid use through the Day 15 Visit.
PK sampling occurred through Day 7. For subjects with drains, all drainage fluid was to be collected and pooled over 12-hour intervals (±1 hour) through 72 hours post-dose for potential measurement of the concentrations of bupivacaine, meloxicam, and other ZYNRELEF components.
During the 72-hour postoperative period, subjects were to receive rescue medication only upon subject request for treating postoperative pain. Prior to the administration of the first dose of rescue medication, if the subject had not already had at least 1 postoperative pain score assessed, then a numeric rating scale (NRS) of pain intensity at rest (NRS-R) score was to be obtained, followed by an NRS of pain intensity with activity (NRS-A) score.
If a subject had not received any opioids or received <5 IV morphine milligram equivalents (MME; eg, <10 mg of oxycodone) within 12 hours prior to discharge, the subject was not to receive an opioid prescription at discharge. If a subject had received ≥5 IV MME within 12 hours prior to discharge, the Investigator could provide the subject with a prescription for PO immediate-release oxycodone tablets: no more than twenty 5 mg immediate-release oxycodone, take 1 to 2 pills (5 to 10 mg) every 4 hours as needed.
- Being tested
- MMA regimen, ZYNRELEF kit components for administration, HTX-011, Bupivacaine Hydrochloride
- Keywords
- postoperative pain, abdominoplasty, multimodal analgesia
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MMA regimenDrug
Also called acetaminophen, ibuprofen
acetaminophen 1 g every 8 hours (q8h) and ibuprofen 400 mg q8h, alternating the 2 medications so that an analgesic was taken approximately every 4 hours (q4h)
ZYNRELEF kit components for administrationDevice
ZYNRELEF kits include sterile, individually packaged components for administration, including vented vial spikes, Luer lock syringes, custom Luer lock applicators, and syringe tip caps.
HTX-011Drug
Also called ZYNRELEF
HTX-011 (bupivacaine/meloxicam) extended-release solution for instillation use, supplied in commercially available ZYNRELEF kits
Bupivacaine HydrochlorideDrug
Bupivacaine HCl (without epinephrine) 0.25%
| Study group | Role | What they receive |
|---|---|---|
| HTX-011 + MMA | Experimental | HTX-011 400 mg/12 mg via instillation + oral (PO) multimodal analgesic (MMA) regimen Receives: Drug: MMA regimen; Device: ZYNRELEF kit components for administration; Drug: HTX-011 |
| Bupivacaine HCl + MMA | Active comparator | Bupivacaine HCl 125 mg via injection + oral (PO) multimodal analgesic (MMA) regimen Receives: Drug: MMA regimen; Drug: Bupivacaine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of TEAEs
Incidence of treatment-emergent adverse events
Measured: Through Day 15
Secondary outcomes (5)
Cmax
Maximum concentration of bupivacaine
Measured: Through 144 hours
Tmax
Time of occurrence of maximum concentration of bupivacaine
Measured: Through 144 hours
AUClast
Area under the concentration-time curve from Time 0 to the time of the last quantifiable concentration of bupivacaine
Measured: Through 144 hours
AUCinf
Area under the concentration-time curve from Time 0 extrapolated to infinity for bupivacaine
Measured: Through 144 hours
t½
Apparent terminal half-life of bupivacaine
Measured: Through 144 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2023
- Study start12 Oct 2021
- Primary completion29 Mar 2022
- Study completion7 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In each cohort, subjects were randomized in a 2:1 ratio to HTX-011 or bupivacaine HCl. All subjects received a scheduled postoperative non-opioid multimodal analgesic (MMA) regimen.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heron Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06109428
- Sponsor's protocol ID
- HTX-011-401 (Cohort 2)
- Other IDs
- Master Protocol: NCT05109312
- Acronym
- AMAZE
- Status last verified
- Oct 2023
- First submitted
- 25 Oct 2023
- Last updated
- 28 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Randomized, Blinded, Active-Controlled Study of HTX-011 in Subjects Undergoing Different Surgical Procedures, Cohort 2: Abdominoplasty
- ClinicalTrials.gov ID
- NCT06109428
- Acronym / sponsor ID
- AMAZE / HTX-011-401 (Cohort 2)
- Keywords
- postoperative pain, abdominoplasty, multimodal analgesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Heron TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 12 Oct 2021 (actual)
- Primary completion
- 29 Mar 2022 (actual)
- Study completion
- 7 Apr 2022 (actual)
- First posted
- 31 Oct 2023 (actual)
- Results
- Posted 28 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cohort 2 (subjects undergoing abdominoplasty) of a Phase 4, randomized, blinded, active-controlled, multicohort study to evaluate HTX-011 compared with bupivacaine HCl in subjects undergoing different surgical procedures
See also the separate record for the master study protocol (NCT05109312).
Detailed description
Subjects were randomized in a 2:1 ratio to have either HTX-011 400 mg/12 mg or bupivacaine HCl 125 mg administered into the surgical site prior to closure. Subjects and study site personnel performing postoperative safety and pharmacodynamic (PD) assessments were blinded to treatment assignments; however, unblinded study site staff were permitted to collect samples for pharmacokinetic (PK) analysis.
During surgery (on Study Day 1), in addition to study drug (HTX-011 or bupivacaine HCl), subjects could receive intravenous (IV) fentanyl, and all subjects were to receive a single dose of either IV morphine or IV hydromorphone just prior to the application of dermal sutures.
Subjects remained in the facility through 72 hours post-dose for safety, PK, and PD assessments. Subjects received a scheduled non-opioid multimodal analgesic (MMA) regimen throughout the 72-hour postoperative period consisting of oral (PO) acetaminophen 1 g every 8 hours (q8h) alternating with PO ibuprofen 400 mg q8h.
After discharge (Day 4), subjects were to continue their scheduled multimodal analgesic (MMA) regimen through Day 7, while awake, and complete the daily diary to record opioid use through the Day 15 Visit.
PK sampling occurred through Day 7. For subjects with drains, all drainage fluid was to be collected and pooled over 12-hour intervals (±1 hour) through 72 hours post-dose for potential measurement of the concentrations of bupivacaine, meloxicam, and other ZYNRELEF components.
During the 72-hour postoperative period, subjects were to receive rescue medication only upon subject request for treating postoperative pain. Prior to the administration of the first dose of rescue medication, if the subject had not already had at least 1 postoperative pain score assessed, then a numeric rating scale (NRS) of pain intensity at rest (NRS-R) score was to be obtained, followed by an NRS of pain intensity with activity (NRS-A) score.
If a subject had not received any opioids or received <5 IV morphine milligram equivalents (MME; eg, <10 mg of oxycodone) within 12 hours prior to discharge, the subject was not to receive an opioid prescription at discharge. If a subject had received ≥5 IV MME within 12 hours prior to discharge, the Investigator could provide the subject with a prescription for PO immediate-release oxycodone tablets: no more than twenty 5 mg immediate-release oxycodone, take 1 to 2 pills (5 to 10 mg) every 4 hours as needed.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- In each cohort, subjects were randomized in a 2:1 ratio to HTX-011 or bupivacaine HCl. All subjects received a scheduled postoperative non-opioid multimodal analgesic (MMA) regimen.
| Arm | Type | Receives |
|---|---|---|
| HTX-011 + MMA | Experimental | Drug: MMA regimen, Device: ZYNRELEF kit components for administration, Drug: HTX-011HTX-011 400 mg/12 mg via instillation + oral (PO) multimodal analgesic (MMA) regimen |
| Bupivacaine HCl + MMA | Active comparator | Drug: MMA regimen, Drug: Bupivacaine HydrochlorideBupivacaine HCl 125 mg via injection + oral (PO) multimodal analgesic (MMA) regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Has American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
- Is scheduled to undergo abdominoplasty.
Key exclusion criteria (14 listed)
- Is undergoing a revision surgery.
- Has a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to bupivacaine (or other local anesthetics), NSAIDs, acetaminophen, oxycodone, morphine, or hydromorphone.
- History of severe allergic reaction to aspirin or other NSAIDs, or known history of severe gastrointestinal adverse reactions associated with NSAID use.
- Has taken meloxicam within 10 days prior to the scheduled surgery, or any NSAID within 24 hours prior to the scheduled surgery, with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
- Opioid use for most days within the last 3 months prior to Screening in the opinion of the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MMA regimenAlso: acetaminophen, ibuprofenacetaminophen 1 g every 8 hours (q8h) and ibuprofen 400 mg q8h, alternating the 2 medications so that an analgesic was taken approximately every 4 hours (q4h) | Drug | Bupivacaine HCl + MMA, HTX-011 + MMA |
| ZYNRELEF kit components for administrationZYNRELEF kits include sterile, individually packaged components for administration, including vented vial spikes, Luer lock syringes, custom Luer lock applicators, and syringe tip caps. | Device | HTX-011 + MMA |
| HTX-011Also: ZYNRELEFHTX-011 (bupivacaine/meloxicam) extended-release solution for instillation use, supplied in commercially available ZYNRELEF kits | Drug | HTX-011 + MMA |
| Bupivacaine HydrochlorideBupivacaine HCl (without epinephrine) 0.25% | Drug | Bupivacaine HCl + MMA |
Primary outcome
Incidence of TEAEs
Time frame: Through Day 15
Incidence of treatment-emergent adverse events
5 secondary outcomes
Cmax
Time frame: Through 144 hours
Tmax
Time frame: Through 144 hours
AUClast
Time frame: Through 144 hours
AUCinf
Time frame: Through 144 hours
t½
Time frame: Through 144 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Postoperative Pain
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
Recruiting
Effect of Cryotherapeutic and Nanotherapeutic Sodium Hypochlorite on Post-Operative Endodontic Pain.
Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
Active, not recruitingPhase 4
Effect of Dexmedetomidine on Postoperative Pain in Spinal Anesthesia for Cesarean Section at Assuit University Hospital
Cesarean Section
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing MMA regimen, ZYNRELEF kit components for administration and HTX-011 in people with Postoperative Pain and Abdominoplasty Surgery, run by Heron Therapeutics at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of TEAEs (time frame: Through Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.