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

AN2 Therapeutics

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: Epetraborole; Drug: Moxifloxacin; Drug: Epetraborole and matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05995444

EBO-104

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. 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

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

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

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

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

12. 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.

13. 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.

14. 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.

15. 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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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24 participants in 4 patient groups, including a placebo group

500 mg epetraborole

Experimental group

Description:

500 mg epetraborole

Treatment:

Drug: Epetraborole

2000 mg epetraborole

Experimental group

Description:

2000 mg epetraborole

Treatment:

Drug: Epetraborole

Epetraborole-matching placebo

Placebo Comparator group

Description:

Epetraborole-matching placebo

Treatment:

Drug: Epetraborole and matching placebo

Drug: Placebo

400 mg moxifloxacin

Active Comparator group

Description:

400 mg moxifloxacin

Treatment:

Drug: Moxifloxacin