P208: A First-in-Human Study Evaluating Safety and Pharmacokinetics in Healthy Participants of the Heavy Metal Chelator HOPO 14-1
Poster Presenter
Laura Magda
Director of Clinical Trials
SRI International United States
Objectives
To evaluate the safety, tolerability, pharmacokinetics, and excretion profile of single ascending doses of HOPO 14-1, an oral capsule formulation of 3,4,3-LI(1,2-HOPO), in cohorts of healthy participants.
Method
This in-progress, open-label, single-center, first-in-human trial is designed to enroll up to 42 healthy male and female participants (7 cohorts of 6) ages 18-65 years. Participants are evaluated for 3 consecutive days/nights with follow-up visits on Days 7 and 14.
Results
Interim data from the first 3 of 7 dose escalation cohorts will be presented from the on-going trial (Clinical Trials.gov identifier NCT05628961). Each cohort of 6 heathy adult participants received a single oral administration of 100, 200, or 500 mg of the actinide decorporation agent 3,4,3-LI(1,2-HOPO) on Day 1 after an overnight fast. Minor, resolved, Grade 1, adverse events possibly related to the investigative agent included headache, nausea, dyspepsia, diarrhea, and creatine kinase elevation. Physical exams (including vital signs, pulse oximetry, and postural hypotension), blood and urine analysis, and electrocardiograms revealed no clinically meaningful findings over the 14-day evaluation period. Levels of 3,4,3-LI(1,2-HOPO) analyte in plasma and urine were determined using validated bioanalytical LC-MS/MS methods with a lower limit of quantification (LLOQ) of 5.0 ng/ml. Dose-dependent levels >LLOQ were observed in plasma up to 9-hour post-dose, and <1% of dose was recovered in urine within 48 h post-dose.
Conclusion
The clinical formulation of the actinide decorporation agent 3,4,3-LI(1,2-HOPO), referred to as HOPO 14-1, is under development as a chelating agent for the treatment of individuals with known or suspected internal contamination with Pu, Am, Cm, U, or Np. To date, oral administration of HOPO 14-1 capsules, at doses of 100, 200, or 500 mg is well tolerated in male and female healthy participants. Continued dose escalation at levels of 1200, 2500, 5000 and 7500 mg are to follow with safety committee assessments occurring before each successive escalation round. HOPO 14-1 will potentially fill an unmet medical need as a shelf-stable, orally administered, broad-spectrum radionuclide chelating agent for the treatment of internal radionuclide contamination. This project is being supported with Federal funds awarded to SRI International from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services under contract 75N93020D00011.
