A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics (PK), Safety, and Tolerability of Epetraborole Tablets and the Impact of Alcohol Dehydrogenase (ADH) Genotype on the PK of Epetraborole and Metabolite M3 in Healthy Japanese Adult Subjects

JRCT ID: jRCT2071220004

Registered date:22/04/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Mycobacterium avium complex (MAC) lung disease
• Date of first enrollment: 18/06/2022
• Target sample size: 18
• Study type: Interventional

Intervention(s)

ADH1B genotype *1/*1: A single Epetraborole 500 mg orally
ADH1B genotype *1/*2: A single Epetraborole 500 mg orally
ADH1B genotype *2/*2: A single Epetraborole 500 mg orally

Outcome(s)

• Primary Outcome: To evaluate the PK of epetraborole and the impact of ADH genotype on the PK of epetraborole and metabolite M3 in healthy Japanese subjects.
• Secondary Outcome: To evaluate the safety and tolerability of epetraborole in healthy Japanese subjects, based on adverse events (AEs), laboratory tests, electrocardiograms (ECGs), physical examinations, and vital signs.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

1. Healthy adult male and/or female of 18 to 65 years of age at the time of signing of informed consent
2. Willing and able to provide written informed consent
3. Body mass index >=18.5 and <=28.0 kg/m2 and weight between 45.0 kg and 100.0 kg (inclusive) at Screening
4. Medically and hemodynamically stable without CS abnormalities at Screening and Day -1, based on physical examination, vital signs, 12 lead ECGs, and laboratory results
5. Light, non-, or ex-smoker (A light smoker is defined as someone using <= 5 cigarettes or less per day for at least 90 days prior to study drug administration. An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to study drug administration.)
6. Agrees not to consume alcohol throughout the study (through the F/U Visit)
7. Willing and able to comply with all study assessments and adhere to the protocol schedule, including the entire confinement period and through the F/U Visit
8. Has suitable venous access for blood sampling
9. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and on Day -1 and be willing to have additional pregnancy tests, as required, throughout the study. To be considered of nonchildbearing potential, a female must have either a tubal ligation, hysterectomy, bilateral salpingo-oophorectomy, or menopause (last menstruation >12 months and follicle-stimulating hormone levels >=40 mIU /mL at Screening); provision of written documentation is not required for female sterilization and oral confirmation is adequate.
10. WOCBP must agree to and comply with using 1 barrier method (eg, female condom or male partner using a condom) plus 1 other highly effective and approved method of birth control in Japan (eg, oral contraceptive pills [OCPs]), or sexual abstinence, for the duration of the study (from signing of consent through the F/U Visit) and for 30 days after study drug administration. Female subjects who are in same-sex relationships are not required to use contraception.
11. WOCBP must agree not to donate ova or oocytes (ie, human eggs) for the duration of the study (from signing of consent through the F/U Visit) and for 1 menstrual cycle after completion of the study.
12. Males must be surgically sterile (>30 days since vasectomy), abstinent, or if engaged in sexual relations with a WOCBP, the subject and his partner must be surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from Screening until study completion (through the F/U Visit). Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner that includes the following: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, or an intrauterine device. Subjects with same-sex partners are eligible when this is their preferred and usual lifestyle.
13. Males must agree to not donate sperm for the duration of the study (from signing of consent through the F/U Visit) and for 90 days after study drug administration.
14. Subjects must agree to adhere to the current advice from the Japanese health authority of Ministry of Health, Labour and Welfare regarding minimizing exposure to coronavirus disease 2019 (COVID 19) from Screening through the F/U Visit.

Exclude criteria

1. History of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease, including any acute illness or major surgery within the past 6 months determined by the Investigator to be CS
2. Unable to swallow solid, PO tablets whole with the aid of water
3. Positive test for HIV, hepatitis B surface antigen, or hepatitis C virus antibody, or test positive for COVID-19 infection
4. Positive drug/alcohol testing at Screening or prior to study drug administration unless the positive drug screen is due to prescription drug use that is approved by the Investigator and the Sponsors Medical Monitor.
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 Screening
6. Use of any prescription medication or any over-the-counter medication, including erythropoietin-stimulating agents, herbal products, and vitamins, within 7 days prior to study drug administration
Note: An exception is made for hormonal contraceptives and intermittent, as-needed acetaminophen or nonsteroidal anti inflammatory drugs for the treatment of transient headache or any other minor ache/pain. Discussion between the Investigator and the Sponsors Medical Monitor is encouraged regarding the acceptability of the prior use of any medications during the study.
7. Any vaccinations or planned vaccinations (including COVID-19 and influenza) within 30 days (within 14 days only for COVID-19 vaccine) prior to dosing on Day 1 and for the duration of the study (through the F/U Visit)
8. Documented significant hypersensitivity reaction or anaphylaxis to any medication, which, in the opinion of the Investigator, could compromise subject safety
9. Subjects with hemoglobin <10.0 g/dL or <6.2 mmol/L (Grade 2 anemia or worse, based on Common Terminology Criteria for Adverse Events criteria) at Screening
10. Subjects who have donated blood or plasma within 28 days prior to Screening or have had symptomatic loss of blood or hemorrhage within 28 days prior to Screening
11. Subjects with severe hepatic impairment, as evidenced by alanine aminotransferase or aspartate aminotransferase > 3 x upper limit of normal (ULN) or total bilirubin > 2 x ULN, or clinical signs of cirrhosis or end stage hepatic disease (eg, ascites, hepatic encephalopathy)
12. Subjects who are pregnant or breastfeeding
13. Subjects with a mean QTcF >480 msec based on triplicate 12-lead ECGs at Screening
14. Received an investigational intervention (including an investigational vaccine) or used an invasive investigational medical device within 30 days (or 5 half-lives whichever is longer) prior to Day 1
15. Prior exposure to epetraborole
16. Any other condition or prior therapy, which, in the opinion of the Investigator, would make the subject unsuitable for this study, including unable to cooperate fully with the requirements of the protocol or likely to be noncompliant with any study requirements

Related Information

• Primary Sponsor: Kanmuri Kazuhiro