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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Toxicity;Chemical
• Intervention / Treatment: Drug: HOPO 14-1

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: 734-527-4200; Email: clinical-trials@sri.com
• Study Contact Backup: Name: Director Clinical Operations; Phone Number: 734-527-4200; Email: clinical-trials@sri.com

Study Locations

• United States
  • Michigan
    • Plymouth, Michigan, United States, 48170
      • Recruiting
      • SRI Biosciences Clinical Trials Unit
      • Contact: Clinical Site Manager; Phone Number: 734-527-4200; Email: clinical-trials@sri.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: 100 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.
Experimental: Cohort 2: 200 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.
Experimental: Cohort 3: 500 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.
Experimental: Cohort 4: 1200 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.
Experimental: Cohort 5: 2500 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.
Experimental: Cohort 6: 5000 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.
Experimental: Cohort 7: 7500 mg; Participants receive an oral single dose of HOPO 14-1 in the fasted condition on Day 1.	Drug: HOPO 14-1; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: SRI International
• Investigators: Principal Investigator: Principal Investigator, SRI International

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Internal Radionuclide Contamination
• Other Study ID Numbers: SRI-HOPO-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No