Inclusion Criteria:
1. Willing to adhere to study procedures and provide written informed consent prior to
the start of any study procedures.
2. 18-45 years of age at the time of consent and in good physical health based on medical
history, physical examination including vital signs, as well as laboratory,
electrocardiogram (ECG), Echocardiography (LVEF in the normal range of 50-70%), normal
muscle strength upon physical examination, and spirometry test values in the normal
range.
3. Weight ≥50 kg and body mass index (BMI) <33 kg/m2.
4. Females or males with female partners must use a medically accepted contraceptive
regimen (i.e., condoms with spermicide, abstinence, nonhormonal intrauterine device
(IUD), Essure procedure, or diaphragm with spermicide) from at least 30 days prior to
first dose through 90 days after the last dose OR females must be of non-childbearing
potential, defined as:
1. Have been surgically sterilized (bilateral oophorectomy) or hysterectomized at
least 6 months prior to screening. Surgical sterilization procedures or
hysterectomy must be supported with clinical documentation/medical records and
noted in the Relevant Medical History/Current Medical Condition section of the
electronic case report form (eCRF).
2. Be postmenopausal (i.e., must have no regular menstrual bleeding for at least 2
years prior to inclusion). Menopause will be confirmed by a plasma
follicle-stimulating hormone (FSH) level of >40 IU/L.
5. Non-smoker and must not have used any tobacco products within 3 months prior to
screening.
6. In good physical and mental health as determined by past medical history, physical
examination, psychiatric examination, 12-lead ECG, Echocardiography, spirometry,
urinary system ultrasound, vital sign measurements, and clinical laboratory
evaluations and calculations(e.g., eGFR greater than 90 ml/1.73 m2) at screening or
check-in to the clinical research unit (CRU) on Day -1, as assessed by the
Investigator (or designee). Congenital nonhemolytic hyperbilirubinemia; or suspicion
of Gilbert's syndrome based on total and direct bilirubin is not acceptable.
7. Has clinical laboratory test results within the reference ranges of the testing
laboratory, except for results outside reference ranges that are deemed not clinically
significant by the Investigator (or designee) at screening and check-in to the CRU on
Day -1.
8. Vital signs are within normal limits and FVC (after 3 minutes resting in supine
position, will be measured in the seated position) is greater than 90% of the
predicted value for gender, age and height with good expiratory effort.
Exclusion Criteria. Subjects who meet any of the following exclusion criteria will be excluded from
participation in the study:
1. History of, or physical examination findings indicating, clinically significant
endocrine, neurological, gastrointestinal, cardiovascular, hematological, hepatic,
immunological, renal, respiratory, genitourinary, or muscle abnormalities or diseases
that, in the opinion of the Investigator, would render the subject being unsuitable
for the study.
2. Unwilling or unable to refrain from strenuous exercise for 3 days prior to check-in
and during study.
3. Unwilling to discontinue coffee (containing caffeine) and other caffeine-containing
beverages (e.g., sodas, energy drinks) for at least 72 hours before check-in and
throughout the entirety of the study.
4. Use of tobacco- or nicotine-containing products (including but not limited to
cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or
nicotine gum) within 3 months prior to check-in to the CRU on Day -1 and throughout
the entirety of the study (urine cotinine levels will be measured during screening for
all subjects; subjects with cotinine values greater than 500 ng/mL will be excluded).
5. Requires prescription or nonprescription medications/herbal remedies/supplements of
any kind (with the exception of paracetamol/acetaminophen 2 g/day for up to 3
consecutive days) from 14 days prior to check-in (Day -1) and throughout the entirety
of the study; uses or intends to use any medications/products known to alter drug
absorption, metabolism, or elimination processes, including St. John's wort, within 30
days prior to dosing.
6. History or clinical manifestation of any metabolic, allergic, dermatological, hepatic,
renal, urinary, hematological, pulmonary, gastrointestinal, neurological, psychiatric,
respiratory, or endocrine disorder, unless determined by the Investigator (or
designee) and agreed by the Medical Monitor to be not clinically significant.
7. Active or history of metabolic, cardiovascular, or cerebrovascular disease, including
hypertension, angina, ischemic heart disease, transient ischemic attacks, bundle
branch block, evidence of myocardial ischemia, stroke, and peripheral arterial disease
sufficient to cause symptoms and/or require therapy to maintain stable status.
8. History of significant hypersensitivity, intolerance, or allergy to any drug compound,
food, or other substance, unless approved by the Investigator (or designee).
9. Active neoplastic disease or history of any neoplastic disease within 5 years of
screening (except for basal or squamous cell carcinoma of the skin or carcinoma in
situ that has been definitively treated with standard of care).
10. Active infection (e.g., sepsis, pneumonia, abscess) or a serious infection (e.g.,
resulting in hospitalization or requiring parenteral antibiotic treatment) within 6
weeks prior to dosing.
11. History of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs (uncomplicated appendectomy
and hernia repair will be allowed).
12. Any of the following at screening and/or pre-dose:
1. QT interval corrected for heart rate using Fridericia's formula (QTcF), QRS
duration, PR interval outside of normal limits confirmed by repeat measurement,
unless deemed non-clinically significant by PI and agreed by Medical Monitor. 2. Findings which would make QTc measurements difficult or QTc data uninterpretable. 3. History of additional risk factors for Torsades de Pointes (e.g., heart failure,
hypokalemia, family history of long QT syndrome)
13. History of alcoholism or drug/chemical abuse.
14. Unwilling to abstain from alcohol consumption within 24 hours of check-in to the CRU
on Day -1 throughout the study.
15. Positive urine alcohol screen or positive urine drug screen (including cannabinoids,
amphetamines, cocaine, opiates benzodiazepines, or barbiturates), including cotinine
(confirmed by repeat) at screening or check-in to the CRU on Day -1.
16. Positive hepatitis panel and/or positive human immunodeficiency virus test at
screening.
17. Any of the following hematology values at screening or check-in to the CRU on Day -1,
as confirmed by 1 repeat if necessary:
1. Hemoglobin <11 g/dL for females, and <12 g/dL for males. 2. Absolute neutrophil count (ANC) <1.5 × 109/L (<1500/μL).
3. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl
transferase (GGT), alkaline phosphatase (ALP), or total bilirubin >1.5 × upper
limit of normal (ULN) at screening or check-in to the CRU on Day -1, confirmed by
1 repeat if necessary.
18. Participation in a clinical study involving administration of an investigational drug
(new chemical entity) or medical device within the last 90 days or 5 half-lives of the
investigational medication, whichever is longer, prior to dosing.
19. Use or intention to use any prescription or nonprescription medications/products
within 14 days or 5 half-lives of the medication/product, whichever is longer, prior
to check-in to the CRU on Day -1 (hormone replacement therapy or intrauterine
contraceptives are acceptable).
20. Receipt of blood products within 2 months prior to check-in to the CRU on Day -1.
21. Donation of blood (>400 mL) or comparable blood loss (>350 mL) from 3 months prior to
screening, plasma donation from 2 weeks prior to screening, or platelets donation from
6 weeks prior to screening.
22. Poor peripheral venous access.
23. Consumption of any foods or beverages containing Seville-type oranges, grapefruit, or
poppy seeds within 7 days prior to check-in to the CRU on Day -1.
24. Subjects who, in the opinion of the Investigator (or designee; including input from
subjects' general practitioner, as applicable), should not participate in this study.
25. Subject hospitalized for any reason in a period of 30 days before the start of the
study.
26. Diagnosis with a primary muscle disorder.
27. The presence of any medical device which may interfere with or be impacted by magnetic
stimulation.
28. History of any suicidal behavior in lifetime or suicidal ideation within the last 2
years, with or without a plan at screening or check-in (Day -1).
29. Subjects who are investigational site staff members or directly involved in the
conduct of the study and their family members or subjects who are employed by the
Sponsor.
30. An IPSS score equal to or greater than 6 at baseline.
