Study of Single Oral Doses of HOPO 14-1 Evaluating Safety, Tolerability, Pharmacokinetics

Study Overview
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Brief Summary
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The study objectives are to define the safety and tolerability profile of oral, single ascending dose (SAD) levels of HOPO 14-1 capsules in cohorts of healthy participants and to assess the pharmacokinetic (PK) and excretion profile of HOPO 14-1. The study hypothesis is that a single dose of HOPO 14-1 will be safe and tolerable up to 7500 mg.

Detailed Description
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The currently available therapy for radionuclide internal contamination is suboptimal. Pharmacological and toxicological data support the clinical development of HOPO 14-1 for decorporation of radionuclides.

Official Title
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An Open-Label, First-In-Human Study of Single Oral Doses of HOPO 14-1 Evaluating Safety, Tolerability, Pharmacokinetics, and Excretion in Healthy Participants

Conditions
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Toxicity;Chemical

Intervention / Treatment
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* Drug: HOPO 14-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability of participant to understand the requirements of the study, provide written informed consent, and agree to abide by the study requirements Agree to use contraception from time of screening until 14 days after dosing (Day 14) if female is of childbearing potential or male is with female partner of childbearing potential. In good general health based on medical history, physical examination (PE), and screening evaluations. Negative urine or blood screen for drugs of abuse (except if participant provides prescription justifying use prior to urine screen). Body weight ≥ 50 kilogram (kg) and ≤ 110 kg. If body weight is over 110 kg, then body mass index (BMI) will be considered and must be ≤ 40 kg/m^2. Exclusion Criteria: Inability or unwillingness of a participant to give written informed consent or comply with study protocol. Any hematology, chemistry, coagulation, or urinalysis value on screening labs defined in the United States Food and Drug Administration (FDA) Guidance for Industry Toxicity Grading Scale as Grade 1 or higher. Any clinically significant electrocardiogram (ECG) abnormality Pregnant or breastfeeding Active substance abuse or history of any medical or psychiatric condition that would jeopardize the participant's safety or the participant's ability to comply with the protocol. Received an organ transplant (solid or bone marrow). Received a blood transfusion within 3 months of dosing. Difficulty swallowing tablets or capsules. Febrile illness or significant infection within 7 days of dosing. Symptoms of hypotension (lightheadedness, syncope, balance disturbances, or extreme fatigue) within 48 hours of dosing. Hepatitis B virus surface antigen (HBsAg) positive or serologic (antibody positive) evidence of infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Tested positive for SARS-CoV-2 (COVID-19) within 21 days of dosing. Chelation therapy (e.g., ethylenediaminetetraacetic acid [EDTA], diethylenetriamine pentaacetate [DTPA]) in the past year. Use of laxatives, antibiotics, and/or antacids within 7 days of dosing. Use of investigational drugs within 60 days of dosing or 5 half-lives, whichever is longer. Received a vaccination within 30 days of dosing. Potential allergic reaction to product (oleic acid or HOPO 14-1 product). Past or current medical problems or findings from physical examination (PE) or laboratory testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 100 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|
| Experimental: Cohort 2: 200 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|
| Experimental: Cohort 3: 500 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|
| Experimental: Cohort 4: 1200 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|
| Experimental: Cohort 5: 2500 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|
| Experimental: Cohort 6: 5000 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|
| Experimental: Cohort 7: 7500 mg<br>Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1. | Drug: HOPO 14-1<br>* HOPO 14-1 contains the active pharmaceutical ingredient (API) 3, 4, 3-LI(1, 2-HOPO) formulated with a permeability enhancer, sodium oleate, in capsule form.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Adverse Events |  | Up to 14 days | 
| Number of Participants with One or More Drug-Related Adverse Events |  | Up to 14 days | 
| Number of Participants with One or More Adverse Events by Maximum Severity |  | Up to 14 days | 
| Number of Participants with One or More Serious Adverse Events |  | Up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed Maximum Plasma Concentration (Cmax) |  | Up to Day 7 | 
| Observed Time to Reach Cmax (Tmax) |  | Up to Day 7 | 
| Area Under the Plasma Concentration Time Curve up to the Last Blood Collection Time with a Measurable Concentration (AUClast) |  | Up to Day 7 | 
| Extrapolated to Infinity (AUC0-inf) |  | Up to Day 7 | 
| Terminal Half-Life (t 1/2) |  | Up to Day 7 | 
| Apparent Volume of Distribution after Oral Administration (V/F) |  | Up to Day 7 | 
| Oral Systemic Clearance Rate (CL/F) |  | Up to Day 7 | 
| Cumulative Amount Excreted in Urine |  | Up to Day 7 | 
| Cumulative Amount Excreted in Feces |  | Up to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Internal Radionuclide Contamination