3 Key Takeaways
Plain English Summary- 01Core Finding
Participants were recruited and screened between March 2023 and July 2025 and follow-up was completed in August 2025.
- 02Study Evidence
Tested in a early human trial at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
What This Means for You
Single oral doses of HOPO 14-1 up to 7500 mg were administered without dose-limiting toxicity or serious adverse events in healthy adults. Gastrointestinal tolerability defined the practical single-dose ceiling. These findings establish the first human safety and pharmacokinetic profile of a novel, orally administered actinide chelator and support further clinical evaluation of HOPO 14-1 as a countermeasure for internal radionuclide and heavy metal contamination. Development of a deployable and population-level emergency intervention addresses a long-standing unmet need with important implications for public health preparedness.
The Discovery
To evaluate the safety, tolerability, pharmacokinetic parameters, and excretion of a single dose of HOPO 14-1 in healthy adults.
This was a Phase 1 nonrandomized clinical trial including 42 healthy adults (6 per dose level) with evaluations for 14 days after administration of a single dose and conducted at a single site in the US. Participants were recruited and screened between March 2023 and July 2025 and follow-up was completed in August 2025.
The primary outcomes were the incidence and severity of adverse events, drug-related adverse events, and serious adverse events. The secondary outcomes were plasma pharmacokinetic parameters and cumulative urinary and fecal excretion.
Of the 42 healthy adults enrolled (median age, 43 [IQR, 34-51] years; 64% female), all received a single dose of HOPO 14-1 (administered across all dose levels as assigned). There were no serious adverse events or dose-limiting toxic effects. The drug-related adverse events included diarrhea, vomiting (14%), headache (12%), and fatigue (7%); all were mild to moderate in severity. Gastrointestinal adverse events were the principal tolerability findings and most evident at the highest doses. The plasma pharmacokinetic parameters demonstrated rapid absorption (median time of maximum plasma concentration, 0.86 [range, 0.53-1.60] hours to 1.90 [range, 1.40-2.90] hours) and dose-dependent increases in systemic exposure, with greater than proportional increases at higher doses. Fecal excretion was the primary route of elimination; urinary excretion was minimal.
How It Works, Simply
This pharmacology research focuses on selective receptor binding & pharmacokinetic optimization. Researchers evaluated it using an early human trial at the Phase I/II stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Participants were recruited and screened between March 2023 and July 2025 and follow-up was completed in August 2025.
- 02Study Evidence
Tested in a early human trial at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Early human trial
Early human trial · Phase I/II
Biological Pathway & Modality
Selective receptor binding & pharmacokinetic optimization
Intervention: HOPO 14-1, an Oral Actinide Chelator: A Phase 1 Nonrandomized Clinical Trial
Experimental Findings & Endpoints
To evaluate the safety, tolerability, pharmacokinetic parameters, and excretion of a single dose of HOPO 14-1 in healthy adults.
This was a Phase 1 nonrandomized clinical trial including 42 healthy adults (6 per dose level) with evaluations for 14 days after administration of a single dose and conducted at a single site in the US. Participants were recruited and screened between March 2023 and July 2025 and follow-up was completed in August 2025.
The primary outcomes were the incidence and severity of adverse events, drug-related adverse events, and serious adverse events. The secondary outcomes were plasma pharmacokinetic parameters and cumulative urinary and fecal excretion.
Of the 42 healthy adults enrolled (median age, 43 [IQR, 34-51] years; 64% female), all received a single dose of HOPO 14-1 (administered across all dose levels as assigned). There were no serious adverse events or dose-limiting toxic effects.
The drug-related adverse events included diarrhea, vomiting (14%), headache (12%), and fatigue (7%); all were mild to moderate in severity. Gastrointestinal adverse events were the principal tolerability findings and most evident at the highest doses.
The plasma pharmacokinetic parameters demonstrated rapid absorption (median time of maximum plasma concentration, 0.86 [range, 0.53-1.60] hours to 1.90 [range, 1.40-2.90] hours) and dose-dependent increases in systemic exposure, with greater than proportional increases at higher doses. Fecal excretion was the primary route of elimination; urinary excretion was minimal.
Clinical Translation & Practice Context
Single oral doses of HOPO 14-1 up to 7500 mg were administered without dose-limiting toxicity or serious adverse events in healthy adults.
Gastrointestinal tolerability defined the practical single-dose ceiling. These findings establish the first human safety and pharmacokinetic profile of a novel, orally administered actinide chelator and support further clinical evaluation of HOPO 14-1 as a countermeasure for internal radionuclide and heavy metal contamination.
Development of a deployable and population-level emergency intervention addresses a long-standing unmet need with important implications for public health preparedness.
The Bottom Line · Clinical Pearl
“Single oral doses of HOPO 14-1 up to 7500 mg were administered without dose-limiting toxicity or serious adverse events in healthy adults. Gastrointestinal tolerability defined the practical single-dose ceiling.”
Published in JAMA · Current Stage: Phase I/II