| Eligibility |
Inclusion Criteria:
- Written informed consent must be obtained before any assessment is performed.
- Age = 18 years and = 55 years, male or female.
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weighs at least 50 kg.
- No clinically significant findings in medical examination, including physical
examination, 12-lead electrocardiogram (ECG) and clinical laboratory tests.
- Male participant and his female spouse/partner who is of childbearing potential agree
to use highly effective contraception* consisting of two forms of birth control (at
least one of which must be a barrier method) from signing of informed consent
throughout the study period and for 90 days after final study drug administration.
- A female subject of childbearing potential who is sexually active agrees to use highly
effective contraception* consisting of two forms of birth control (at least one of
which must be a barrier method) from signing of informed consent throughout the
duration of the study period and for 90 days after last study drug administration. If
the next menstrual period is delayed, a pregnancy test will be required for exclusion
of pregnancy.
- Highly effective contraception is defined as:
- Established use of oral, injected, or implanted hormonal methods of
contraception
- Placement of an intrauterine device or intrauterine system
- Barrier methods of contraception: condom with spermicidal foam, gel, film,
cream, suppository or occlusive cap (diaphragm or cervical/vault caps) with
spermicidal foam, gel, film, cream, or suppository
- Able to understand and sign informed consent and to comply with the protocol
Exclusion Criteria:
- Any history of clinically serious disease.
- Any active or unstable clinically significant medical condition as judged by the
investigator.
- Subject has abnormal Screening findings or Day -2 laboratory value that suggest a
clinically significant underlying disease.
- Hypersensitivity or allergy to any of the study drugs, drugs of similar chemical
classes.
- Received any investigational drug within 30 days or 5x T1/2 whichever is longer before
the Screening.
- Participants who have undergone major surgery = 2 months prior to start study drug.
- Impaired cardiac function including clinically significant arrhythmias or clinically
significant abnormality in clinical test, including but not limited to any of the
following at Screening and
Check-in, repeat testing is allowed for verification, at the discretion of the
Investigator:
- Heart rate < 45 beats per minute (bpm) or > 90 bpm (taken during blood pressure
measurement).
- Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg; diastolic blood pressure (DBP)
< 50 mmHg or > 90 mmHg.
- Average of the 3 QT intervals corrected using Fridericia's formula (QTcF) > 450
milliseconds.
- Second degree or higher Atrioventricular block on ECG
- Estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2
- Impaired renal function or abnormal liver enzymes at baseline, including but not
limited to:
- Alanine aminotransferase (ALT) > upper limit of normal (ULN)
- Aspartate aminotransferase (AST) > ULN
- Estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2
- Women who are pregnant or lactating, or intending to become pregnant before,
during or within 90 days after exit from this study.
- Women with baseline FSH =40mIU/ml
- Participant who has had a loss of more than 100 mL blood (e.g., a blood donation)
within 2 months before study drug administration, or has received any blood,
plasma, or platelet transfusions within 3 months before Check-in, or plans to
donate blood, ova or sperm during the study or within 3 months after the study.
- Participant who has a known history of, or a positive test result for, hepatitis
B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency
virus (HIV) types 1 or 2 at screening.
- Participant who has used prescription or over-the-counter (OTC) medication (other
than =2 g/day paracetamol [acetaminophen] or =800 mg/day ibuprofen), vitamins, or
herbal remedies, within 7 days or 5 half-lives before study drug administration,
whichever is longer.
- Participant who has a history of alcohol abuse (defined as an alcohol intake more
than 21 units per week) or a history of drug abuse within the 6 months before
study drug administration, or a history of substance abuse deemed significant by
the investigator. A unit of alcohol is defined as 240 mL of beer, 120 mL of wine,
or 20 mL of spirits.
- Participant who smokes cigarettes or uses other nicotine-containing products
(e.g., vape, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or
inhalers), has done so in the 3 months prior to screening.
- Consumption of caffeine or xanthine-containing food or beverages from at least 72
hours prior to Check-in to the clinical research unit until at least 24 hours
after last drug administration
- Participant who has a positive test for alcohol or drugs of abuse (amphetamines,
barbiturates, benzodiazepines, MDMA, oxycodone, phencyclidine, methamphetamine,
tricyclic antidepressants, opiates, methadone, cocaine, cannabinoids,
amphetamines, or cotinine) at Screening or Check-in.
- Subject is unable to complete this study for other reasons or the Investigator
believes that he or she should be excluded.
- Participant who has a positive swab test of COVID-19 from Screening or Check-in
testing.
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