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Completed

NCT Number: NCT05995444

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

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.

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Key information

Conditions

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

423001

Tempe, Arizona, 85283, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 1. 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

Exclusion criteria

  • 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.
  • Unable to refrain from or anticipates the use of any drugs, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning

14 days prior to the first dosing.

  • Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing.
  • Donation of blood or blood products or significant blood loss within 56 days prior to the first dosing or plans to donate blood products through the follow-up contact.
  • Participation in another clinical study and received an investigational agent within 30 days or within 5 half-lives (if known), prior to the first dosing, whichever is longer. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.

Treatment and study plan

Epetraborole and matching placebo

Drug

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

Other names: Therapeutic

Epetraborole

Drug

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

Other names: Supratherapeutic

Placebo

Drug

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

Other names: Placebo Control

moxifloxacin

Drug

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

Other names: Positive Control

Primary outcomes

  1. Changes to QTc interval

    Time frame: Study Day -1 to Study Day 2

    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.

Secondary outcomes

  1. Effect of epetraborole plasma concentrations on other ECG parameters on QTc

    Time frame: Study Day -1 to Study Day 2

    Measure the Effect of epetraborole plasma concentrations on other ECG parameters on QTc

  2. Assay sensitivity

    Time frame: Study Day -1 to Study Day 2

    Assay sensitivity assessment with ddQTc at the geometric mean Cmax value predicted from a linear mixed effect model evaluating the relationship between QTc and moxifloxacin plasma concentrations (exposure-response modeling).

  3. Analysis of dQTc

    Time frame: Study Day -1 to Study Day 2

    QTc interval using a mixed effect analysis of covariance (ANCOVA) carried out as appropriate to analyze dQTc at each time point post baseline.

  4. PK Concentration analysis for epetraborole and metabolite M3 of AUC0 t

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of AUC0 t

  5. Evaluation of TEAEs

    Time frame: Study Day 1 through Study Day 14

    TEAEs

  6. Safety Vital Signs changes of body temperature

    Time frame: Study Day 1 through Study Day 14

    Measure Safety Vital Signs changes of body temperature

  7. Orthostatic Vital Signs changes of Heart Rate from supine to standing position.

    Time frame: Study Day 1 through Study Day 14

    Measure Orthostatic Vital Signs changes of Heart Rate from supine to standing position.

  8. Effect of epetraborole plasma concentrations on other ECG parameters on, PR

    Time frame: Study Day -1 to Study Day 2

    Measure the Effect of epetraborole plasma concentrations on other ECG parameters on, PR

  9. Effect of epetraborole plasma concentrations on other ECG parameters on QRS duration

    Time frame: Study Day -1 to Study Day 2

    Measure the Effect of epetraborole plasma concentrations on other ECG parameters on QRS duration.

  10. Effect of epetraborole plasma concentrations on other ECG parameters on HR.

    Time frame: Study Day -1 to Study Day 2

    Measure the Effect of epetraborole plasma concentrations on other ECG parameters on HR.

  11. PK Concentration analysis for epetraborole and metabolite M3 of AUC0 inf

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of AUC0 inf

  12. PK Concentration analysis for epetraborole and metabolite M3 of AUC%extrap

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of AUC%extrap

  13. PK Concentration analysis for epetraborole and metabolite M3 of Cmax

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of Cmax

  14. PK Concentration analysis for epetraborole and metabolite M3 of Tmax

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of Tmax

  15. PK Concentration analysis for epetraborole and metabolite M3 of Kel

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of Kel

  16. PK Concentration analysis for epetraborole and metabolite M3 of t½

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of t½

  17. PK Concentration analysis for epetraborole and metabolite M3 of CL/F (parent only),

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of CL/F (parent only),

  18. PK Concentration analysis for epetraborole and metabolite M3 of Vz/F (parent only)

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of Vz/F (parent only

  19. PK Concentration analysis for epetraborole and metabolite M3 of MR AUC0 t

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of MR AUC0 t

  20. PK Concentration analysis for epetraborole and metabolite M3 of MR AUC0 inf

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of MR AUC0 inf

  21. PK Concentration analysis for epetraborole and metabolite M3 of MR Cmax

    Time frame: Study Day -1 to Study Day 2

    Analysis of PK Concentration for epetraborole and metabolite M3 of MR Cmax

  22. Safety Vital Signs changes of respiratory rate

    Time frame: Study Day 1 through Study Day 14

    Measure Safety Vital Signs changes of respiratory rate

  23. Safety Vital Signs changes of blood pressure

    Time frame: Study Day 1 through Study Day 14

    Measure Safety Vital Signs changes of blood pressure (systolic and diastolic)

  24. Safety Vital Signs changes of heart rate

    Time frame: Study Day 1 through Study Day 14

    measure Safety Vital Signs changes of heart rate

  25. Orthostatic Vital Signs changes of blood pressure from supine to standing position.

    Time frame: Study Day 1 through Study Day 14

    Measure Orthostatic Vital Signs changes of blood pressure from supine to standing position (systolic and diastolic).

Sponsors and collaborators

Lead sponsor

AN2 Therapeutics, Inc

Industry

Registry information

Official study title

A Phase 1, Single-Dose, Randomized, Placebo- and Positive-Control, Four-Way, Crossover Study for the Evaluation of the Effect of Epetraborole on QT Intervals in Healthy Adult Subjects

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Aug 16, 2023
Registry last updated
Dec 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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