Dose-Escalation Study of HTX-034 Following Bunionectomy

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

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

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.