Auxora for the Treatment of Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome: Clinical Development of a Calcium Release-Activated Calcium Channel Inhibitor

Pancreas. 2021 Apr 1;50(4):537-543. doi: 10.1097/MPA.0000000000001793.

Abstract

Objectives: To assess the safety of Auxora in patients with acute pancreatitis (AP), systemic inflammatory response syndrome (SIRS), and hypoxemia, and identify efficacy endpoints to prospectively test in future studies.

Methods: This phase 2, open-label, dose-response study randomized patients with AP, accompanying SIRS, and hypoxemia (n = 21) to receive low-dose or high-dose Auxora plus standard of care (SOC) or SOC alone. All patients received pancreatic contrast-enhanced computed tomography scans at screenings, day 5/discharge, and as clinically required 90 days postrandomization; scans were blinded and centrally read to determine AP severity using computed tomography severity index. Solid food tolerance was assessed at every meal and SIRS every 12 hours.

Results: The number of patients experiencing serious adverse events was not increased with Auxora versus SOC alone. Three (36.5%) patients with moderate AP receiving low-dose Auxora improved to mild AP; no computed tomography severity index improvements were observed with SOC. By study end, patients receiving Auxora better tolerated solid foods, had less persistent SIRS, and had reduced hospitalization versus SOC.

Conclusions: The favorable safety profile and patient outcomes suggest Auxora may be an appropriate early treatment for patients with AP and SIRS. Clinical development will continue in a randomized, controlled, blinded, dose-ranging study.

Trial registration: ClinicalTrials.gov NCT03401190.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use*
  • Calcium Release Activated Calcium Channels / antagonists & inhibitors*
  • Calcium Release Activated Calcium Channels / metabolism
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Pancreatitis / complications
  • Pancreatitis / drug therapy*
  • Respiratory Insufficiency / chemically induced
  • Systemic Inflammatory Response Syndrome / complications
  • Systemic Inflammatory Response Syndrome / drug therapy*
  • Treatment Outcome

Substances

  • Calcium Channel Blockers
  • Calcium Release Activated Calcium Channels
  • Interleukin-6

Associated data

  • ClinicalTrials.gov/NCT03401190