Clinical trial NCT04398329: Dose-Escalation Study of HTX-034 Following Bunionectomy
Official title: A Phase 1b/2, Randomized, Blinded, Active-Controlled Study of Escalating Doses of HTX-034 for Postoperative Analgesia in Subjects Undergoing Unilateral, First Metatarsal Bunionectomy With Osteotomy and Internal Fixation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bunions
Keywords: Analgesia
Bunionectomy
Lead sponsor: Heron Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-05-21
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b/2, randomized, blinded, active-controlled study. Phase 1b will evaluate escalating doses of HTX-034 compared with bupivacaine HCl. Phase 2 will be a dose-expansion phase to evaluate additional subjects treated with the HTX-034 dose selected based on Phase 1b compared with bupivacaine HCl.


Eligibility criteria: Inclusion Criteria:

* Is medically fit to undergo an elective unilateral, first metatarsal bunionectomy with osteotomy and internal fixation under regional anesthesia; no neuraxial technique (eg, no spinal, epidural, or general anesthesia).
* Has an American Society of Anesthesiologists (ASA) 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 contralateral foot bunionectomy in the past 3 months.
* Has a planned concurrent surgical procedure.
* Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
* Has a pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
* Has received or is taking a contraindicated or prohibited medications.
* 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 history of clinically significant cardiac abnormality such as myocardial infarction within 6 months.
* Has a history of coronary artery bypass graft surgery within 12 months.
* Has a history of known or suspected coagulopathy.
* 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.
* 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 known history of glucose-6-phosphate dehydrogenase deficiency.
* Has any of the following laboratory abnormalities during Screening (1 retest permitted):

  * Severe liver function impairment.
  * Severe kidney function impairment.
  * Platelet count \<100,000/μL, hemoglobin \<12 g/dL, or hematocrit \<35%.
* Has a body mass index (BMI) \>39 kg/m2.

Primary outcomes:
measure: Incidence of Treatment-emergent adverse events (TEAE's) (Phase 1B)
timeFrame: 42 days
measure: Mean area under the curve (AUC) of the NRS scores through 72 hours (AUC0-72) for the pooled Phase 1b and Phase 2
timeFrame: 7 days
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of HTX-034
timeFrame: 29 days
measure: Time of maximum plasma concentration (Tmax) of HTX-034
timeFrame: 29 days
measure: Area under the concentration-time curve from Time 0 to the time of the last quantitative concentration (AUClast) of HTX-034
timeFrame: 29 days
measure: Area under the concentration-time curve from Time 0 extrapolated to infinity (AUCinf) of HTX-034 (Phase 1B)
timeFrame: 22 days
measure: Apparent terminal half-life (t½) of HTX-034 (Phase 1B)
timeFrame: 22 days
measure: Mean AUC of the NRS pain intensity scores
timeFrame: 7 days
measure: Total postoperative opioid consumption (in IV Morphine Milligram Equivalents)
timeFrame: 7 days
measure: Proportion of subjects who are opioid-free
timeFrame: 14 days
measure: Incidence of serious adverse Events (SAE's)
timeFrame: 42 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Bellaire
country: United States
facility: First Surgical Hospital
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials, LLC
state: Texas
city: Salt Lake City
country: United States
facility: JBR Clinical Research
state: Utah
Study officials:
References: