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

Sponsor
AN2 Therapeutics, Inc (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT05995444
Collaborator
(none)
24
Enrollment
1
Location
4
Arms
4.9
Anticipated Duration (Months)
4.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
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.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.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official 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
Actual Study Start Date :
Jun 5, 2023
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: 500 mg epetraborole

500 mg epetraborole

Drug: Epetraborole
Treatment B (Supratherapeutic): 2000 mg epetraborole (8 x 250 mg tablets)
Other Names:
  • Supratherapeutic

    		•
    Experimental: 2000 mg epetraborole

    2000 mg epetraborole

    Drug: Epetraborole
    Treatment B (Supratherapeutic): 2000 mg epetraborole (8 x 250 mg tablets)
    Other Names:
  • Supratherapeutic

    		•
    Placebo Comparator: Epetraborole-matching placebo

    Epetraborole-matching placebo

    Drug: Epetraborole and matching placebo
    Treatment A (Therapeutic): 500 mg epetraborole (2 x 250 mg tablets) and epetraborole matching-placebo (6 tablets)
    Other Names:
  • Therapeutic

    • Drug: Placebo
    Treatment C (Placebo control): Epetraborole matching-placebo (8 tablets)
    Other Names:
  • Placebo Control

    		•
    Active Comparator: 400 mg moxifloxacin

    400 mg moxifloxacin

    Drug: Moxifloxacin
    Treatment D (Positive control): 400 mg moxifloxacin (1 x 400 mg tablet)
    Other Names:
  • Positive Control

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Changes to QTc interval [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 Outcome Measures

    1. Effect of epetraborole plasma concentrations on other ECG parameters on QTc [Study Day -1 to Study Day 2]

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

    2. Assay sensitivity [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 [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 [Study Day -1 to Study Day 2]

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

    5. Evaluation of TEAEs [Study Day 1 through Study Day 14]

      TEAEs

    6. Safety Vital Signs changes of body temperature [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. [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 [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 [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. [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 [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 [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 [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 [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 [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 [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), [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) [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 [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 [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 [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 [Study Day 1 through Study Day 14]

      Measure Safety Vital Signs changes of respiratory rate

    23. Safety Vital Signs changes of blood pressure [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 [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. [Study Day 1 through Study Day 14]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
      1. Adult, male or female, 18-65 years of age, inclusive, at the screening visit.

    2. Subjects must agree to follow protocol-specified contraception guidance

    3. Continuous non smoker for at least 3 months prior to the first dosing based on subject self-reporting

    4. Body mass index (BMI) 18.0 and 32.0 kg/m2 at the screening visit.

    5. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the Investigator or designee.

    6. 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:

    1. 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.

    2. 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.

    3. Presence of bacterial infections requiring the use of antibiotic therapy within 3 months prior to the first dosing.

    4. History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.

    5. 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.

    6. 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.

    7. History or presence of any of the following, deemed clinically significant by the

    Investigator or qualified designee:

    1. Ventricular pre-excitation syndrome (Wolff Parkinson White syndrome)

    2. Arrhythmia or history of arrhythmia requiring medical intervention

    3. Risk factors for TdP (e.g., heart failure, cardiomyopathy, family history of Long QT Syndrome, or sudden unexpected cardiac death at a young age)

    4. Sick sinus syndrome, second- or third-degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF interval, or conduction abnormalities

    5. Is lactating or has a positive pregnancy test at the screening visit or first check-in (females only).

    6. Positive urine drug or alcohol results at the screening visit or first check-in.

    7. Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at the screening visit.

    8. Positive results for coronavirus disease 2019 (COVID-19) at first check-in.

    9. 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.

    1. 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.

    2. 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.

    3. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 423001 Tempe Arizona United States 85283

    Sponsors and Collaborators

    • AN2 Therapeutics, Inc

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AN2 Therapeutics, Inc
    ClinicalTrials.gov Identifier:
    NCT05995444
    Other Study ID Numbers:
    • EBO-104
    First Posted:
    Aug 16, 2023
    Last Update Posted:
    Aug 18, 2023
    Last Verified:
    Aug 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by AN2 Therapeutics, Inc
    QTc
    Epetraborole
    Additional relevant MeSH terms:
    Moxifloxacin

    Study Results

    No Results Posted as of Aug 18, 2023