Dose-Escalation Study of HTX-034 Following Bunionectomy

Phase 1

Completed

• Conditions: Bunions
• Interventions: Drug: HTX-034; Drug: Bupivacaine HCl; Device: Luer lock applicator

• Registration Number: NCT04398329
• Lead Sponsor: Heron Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-05-18
• Study First Submitted: 2020-05-18
• Study First Submitted QC: 2020-05-18
• Study First Posted: 2020-05-21
• Primary Completion: 2021-07-01
• Study Completion: 2021-08-03
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-31
• Last Update Posted: 2022-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 73

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 (Expansion): Low Dose	Luer lock applicator	Fixed dose of HTX-034.
Phase 1b (Cohort 1)	HTX-034	Fixed dose of HTX-034.
Phase 1b (Cohort 1)	Luer lock applicator	Fixed dose of HTX-034.
Phase 1b (Cohort 2)	HTX-034	Individualized dose of HTX-034.
Phase 1b (Cohort 2)	Luer lock applicator	Individualized dose of HTX-034.
Phase 2 (Expansion): High Dose	HTX-034	Individualized dose of HTX-034.
Phase 2 (Expansion): Low Dose	HTX-034	Fixed dose of HTX-034.
Phase 2 (Expansion): High Dose	Luer lock applicator	Individualized dose of HTX-034.
Phase 1b and Phase 2	Bupivacaine HCl	Bupivacaine HCl.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-emergent adverse events (TEAE's) (Phase 1B)	42 days
Mean area under the curve (AUC) of the NRS scores through 72 hours (AUC0-72) for the pooled Phase 1b and Phase 2	7 days

Secondary Outcome Measures

Name	Time	Method
Maximum plasma concentration (Cmax) of HTX-034	29 days
Time of maximum plasma concentration (Tmax) of HTX-034	29 days
Area under the concentration-time curve from Time 0 to the time of the last quantitative concentration (AUClast) of HTX-034	29 days
Area under the concentration-time curve from Time 0 extrapolated to infinity (AUCinf) of HTX-034 (Phase 1B)	22 days
Mean AUC of the NRS pain intensity scores	7 days
Apparent terminal half-life (t½) of HTX-034 (Phase 1B)	22 days
Proportion of subjects who are opioid-free	14 days
Incidence of serious adverse Events (SAE's)	42 days
Total postoperative opioid consumption (in IV Morphine Milligram Equivalents)	7 days

Trial Locations

Locations (4)

Endeavor Clinical Trials, LLC; 🇺🇸 San Antonio, Texas, United States

Arizona Research Center; 🇺🇸 Phoenix, Arizona, United States

JBR Clinical Research; 🇺🇸 Salt Lake City, Utah, United States

First Surgical Hospital; 🇺🇸 Bellaire, Texas, United States