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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05995444
• Other study ID #: EBO-104
• Status: Completed
• Phase: Phase 1
• Start date: June 5, 2023
• Est. completion date: August 3, 2023

Study information

• Verified date: August 2023
• Source: AN2 Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 3, 2023
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Epetraborole and matching placebo
Treatment A (Therapeutic): 500 mg epetraborole (2 x 250 mg tablets) and epetraborole matching-placebo (6 tablets)
• Epetraborole
Treatment B (Supratherapeutic): 2000 mg epetraborole (8 x 250 mg tablets)
• Placebo
Treatment C (Placebo control): Epetraborole matching-placebo (8 tablets)
• Moxifloxacin
Treatment D (Positive control): 400 mg moxifloxacin (1 x 400 mg tablet)

Locations

Country	Name	City	State
United States	423001	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AN2 Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Effect of epetraborole plasma concentrations on other ECG parameters on QTc	Measure the Effect of epetraborole plasma concentrations on other ECG parameters on QTc	Study Day -1 to Study Day 2
Secondary	Assay sensitivity	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).	Study Day -1 to Study Day 2
Secondary	Analysis of dQTc	QTc interval using a mixed effect analysis of covariance (ANCOVA) carried out as appropriate to analyze dQTc at each time point post baseline.	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of AUC0 t	Analysis of PK Concentration for epetraborole and metabolite M3 of AUC0 t	Study Day -1 to Study Day 2
Secondary	Evaluation of TEAEs	TEAEs	Study Day 1 through Study Day 14
Secondary	Safety Vital Signs changes of body temperature	Measure Safety Vital Signs changes of body temperature	Study Day 1 through Study Day 14
Secondary	Orthostatic Vital Signs changes of Heart Rate from supine to standing position.	Measure Orthostatic Vital Signs changes of Heart Rate from supine to standing position.	Study Day 1 through Study Day 14
Secondary	Effect of epetraborole plasma concentrations on other ECG parameters on, PR	Measure the Effect of epetraborole plasma concentrations on other ECG parameters on, PR	Study Day -1 to Study Day 2
Secondary	Effect of epetraborole plasma concentrations on other ECG parameters on QRS duration	Measure the Effect of epetraborole plasma concentrations on other ECG parameters on QRS duration.	Study Day -1 to Study Day 2
Secondary	Effect of epetraborole plasma concentrations on other ECG parameters on HR.	Measure the Effect of epetraborole plasma concentrations on other ECG parameters on HR.	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of AUC0 inf	Analysis of PK Concentration for epetraborole and metabolite M3 of AUC0 inf	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of AUC%extrap	Analysis of PK Concentration for epetraborole and metabolite M3 of AUC%extrap	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of Cmax	Analysis of PK Concentration for epetraborole and metabolite M3 of Cmax	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of Tmax	Analysis of PK Concentration for epetraborole and metabolite M3 of Tmax	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of Kel	Analysis of PK Concentration for epetraborole and metabolite M3 of Kel	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of t½	Analysis of PK Concentration for epetraborole and metabolite M3 of t½	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of CL/F (parent only),	Analysis of PK Concentration for epetraborole and metabolite M3 of CL/F (parent only),	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of Vz/F (parent only)	Analysis of PK Concentration for epetraborole and metabolite M3 of Vz/F (parent only	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of MR AUC0 t	Analysis of PK Concentration for epetraborole and metabolite M3 of MR AUC0 t	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of MR AUC0 inf	Analysis of PK Concentration for epetraborole and metabolite M3 of MR AUC0 inf	Study Day -1 to Study Day 2
Secondary	PK Concentration analysis for epetraborole and metabolite M3 of MR Cmax	Analysis of PK Concentration for epetraborole and metabolite M3 of MR Cmax	Study Day -1 to Study Day 2
Secondary	Safety Vital Signs changes of respiratory rate	Measure Safety Vital Signs changes of respiratory rate	Study Day 1 through Study Day 14
Secondary	Safety Vital Signs changes of blood pressure	Measure Safety Vital Signs changes of blood pressure (systolic and diastolic)	Study Day 1 through Study Day 14
Secondary	Safety Vital Signs changes of heart rate	measure Safety Vital Signs changes of heart rate	Study Day 1 through Study Day 14
Secondary	Orthostatic Vital Signs changes of blood pressure from supine to standing position.	Measure Orthostatic Vital Signs changes of blood pressure from supine to standing position (systolic and diastolic).	Study Day 1 through Study Day 14