A Study to Assess the Effects of Epetraborole on the QT Interval in Healthy Adult Subjects

NCT05995444 | Completed Phase 1 FDA Drug

• 1 other identifier: EBO-104
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A single-center, 4-way crossover study to evaluate the effect of single therapeutic and supratherapeutic oral doses of epetraborole on the heart rate (HR) corrected QT interval (QTc) by assessing concentration-QT (C-QT) relationship using exposure-response modeling.

Conditions

Healthy Volunteers

Keywords

QTc; Epetraborole

Outcome Measures

Primary Outcomes (1)

• Changes to QTc interval

  Effect of epetraborole plasma concentrations on the QTc interval using linear mixed effect exposure-response modeling, including the predicted ddQTc at Cmax values corresponding to exposure levels of interest.

  Study Day -1 to Study Day 2

Secondary Outcomes (25)

• Effect of epetraborole plasma concentrations on other ECG parameters on QTc

  Study Day -1 to Study Day 2

• Assay sensitivity

  Study Day -1 to Study Day 2

• Analysis of dQTc

  Study Day -1 to Study Day 2

• PK Concentration analysis for epetraborole and metabolite M3 of AUC0 t

  Study Day -1 to Study Day 2

• Evaluation of TEAEs

  Study Day 1 through Study Day 14

Study Arms (4)

500 mg epetraborole

EXPERIMENTAL

500 mg epetraborole

Drug: Epetraborole

2000 mg epetraborole

EXPERIMENTAL

2000 mg epetraborole

Drug: Epetraborole

Epetraborole-matching placebo

PLACEBO COMPARATOR

Epetraborole-matching placebo

Drug: Epetraborole and matching placebo; Drug: Placebo

400 mg moxifloxacin

ACTIVE COMPARATOR

400 mg moxifloxacin

Drug: Moxifloxacin

Interventions

Epetraborole and matching placebo DRUG

Treatment A (Therapeutic): 500 mg epetraborole (2 x 250 mg tablets) and epetraborole matching-placebo (6 tablets)

Also known as: Therapeutic

Epetraborole-matching placebo

Epetraborole DRUG

Treatment B (Supratherapeutic): 2000 mg epetraborole (8 x 250 mg tablets)

Also known as: Supratherapeutic

2000 mg epetraborole; 500 mg epetraborole

Placebo DRUG

Treatment C (Placebo control): Epetraborole matching-placebo (8 tablets)

Also known as: Placebo Control

Epetraborole-matching placebo

Moxifloxacin DRUG

Treatment D (Positive control): 400 mg moxifloxacin (1 x 400 mg tablet)

Also known as: Positive Control

400 mg moxifloxacin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Adult, male or female, 18-65 years of age, inclusive, at the screening visit.
• Subjects must agree to follow protocol-specified contraception guidance
• Continuous non smoker for at least 3 months prior to the first dosing based on subject self-reporting
• Body mass index (BMI) 18.0 and 32.0 kg/m2 at the screening visit.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the Investigator or designee.
• No clinically significant history or presence of ECG findings as judged by the Investigator or designee at the screening visit and first check-in

You may not qualify if:

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• Presence of bacterial infections requiring the use of antibiotic therapy within 3 months prior to the first dosing.
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (e.g., fluoroquinolones, epetraborole excipients), or allergy to ECG electrode adhesive patches or adhesive dressings/medical tape.
• History or presence of any of the following, deemed clinically significant by the Investigator or qualified designee:
• Ventricular pre-excitation syndrome (Wolff Parkinson White syndrome)
• Arrhythmia or history of arrhythmia requiring medical intervention
• Risk factors for TdP (e.g., heart failure, cardiomyopathy, family history of Long QT Syndrome, or sudden unexpected cardiac death at a young age)
• Sick sinus syndrome, second- or third-degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities
• Is lactating or has a positive pregnancy test at the screening visit or first check-in (females only).
• Positive urine drug or alcohol results at the screening visit or first check-in.
• Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at the screening visit.
• Positive results for coronavirus disease 2019 (COVID-19) at first check-in.

Sponsors & Collaborators

• AN2 Therapeutics, Inc: lead

Study Sites (1)

423001

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Therapeutics; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Screening of subjects will occur within 28 days prior to the first dosing. Subjects will be housed on Day -1, at the time indicated by the CRU, until completion of study procedures on Day 2 of each period. On Day 1 of each period, subjects will receive 1 of 4 treatments: a single therapeutic dose of epetraborole (Treatment A), a single supratherapeutic dose of epetraborole (Treatment B), a single dose of epetraborole matching-placebo (Treatment C), or a single dose of moxifloxacin (Treatment D). Cardiodynamic ECGs and PK blood samples for epetraborole, metabolite M3, and moxifloxacin (as applicable) will be collected predose and for 24 hours postdose in each period. There will be a washout of at least 10 days between doses. Safety will be monitored throughout the study by repeated clinical and laboratory evaluations, including a follow-up visit approximately 14 days after the last dose.

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: August 16, 2023
• Study Start: June 5, 2023
• Primary Completion: July 26, 2023
• Study Completion: August 3, 2023
• Last Updated: December 21, 2023

Record last verified: 2023-08

Locations

US (1)