| Eligibility |
Inclusion Criteria:
1. Healthy adult male and/or female (non-childbearing potential only), 19 to 55 years of
age, inclusive, at screening.
2. Continuous non-smoker who has not used nicotine-containing products for at least 3
months prior to the first dose and throughout the study.
3. Body mass index (BMI) = 18.5 and = 32.0 (kg/m2) at screening and weight = 50 kg at
screening.
4. Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs or ECGs, as deemed by the PI.
5. No clinically significant history or presence of ECG findings as judged by the PI or
qualified designee at screening and check-in.
6. For a female, must be of non-childbearing potential and therefore must have undergone
one of the following sterilization procedures, at least 6 months prior to the first
dose:
1. hysteroscopic sterilization;
2. bilateral tubal ligation or bilateral salpingectomy;
3. hysterectomy;
4. bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year
prior to the first dose and follicle-stimulating hormone (FSH) serum levels
consistent with postmenopausal status as per PI judgment.
7. A non-vasectomized, male subject must agree to use a condom with spermicide or abstain
from sexual intercourse during the study until 90 days beyond the last dose of study
drug. (No restrictions are required for a vasectomized male provided his vasectomy has
been performed 4 months or more prior to the first dose of study drug. A male who has
been vasectomized less than 4 months prior to the first dose must follow the same
restrictions as a non-vasectomized male).
8. If male, must agree to not donate sperm from the first dose until 90 days after
dosing.
9. Must have the ability to understand and sign a written informed consent form, which
must be obtained prior to initiation of study procedures.
Exclusion Criteria:
1. Subject 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 in the opinion of the PI.
3. History of any illness that, in the opinion of the PI, might confound the results of
the study or poses an additional risk to the subject by their participation in the
study.
4. History or presence of alcoholism or drug abuse within the past 2 years prior to the
first dose or regular alcohol consumption within 6 months prior to the first dose with
an average weekly intake of greater than 21 glasses/units per week for males or 14
glasses/units per week for females, with one unit = 150 mL of wine or 360 mL of beer
or 45 mL of 45% alcohol.
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s)
or related compounds.
6. History of sensitivity to heparin or heparin-induced thrombocytopenia.
7. Active or latent tuberculosis.
8. Estimated creatinine clearance <80 mL/min at screening.
9. Liver function tests (serum ALT, AST, alkaline phosphatase) and serum bilirubin (total
and direct) > ULN.
10. Absolute neutrophil count < 1500 cells/mm3.
11. White blood cell count < 3500 cells/mm3.
12. Haemoglobin levels < 0.5 mg/dL below the lower limit of normal.
13. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
14. Female subjects of childbearing potential.
15. Female subjects who are pregnant or lactating.
16. Positive urine drug or alcohol results at screening or check-in.
17. Positive urine cotinine at screening.
18. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B
surface antigen (HBsAg), or hepatitis C antibodies (HCV).
19. Unable to refrain from or anticipates the use of any drug, including prescription and
non-prescription medications, herbal remedies, or vitamin supplements beginning
approximately 14 days prior to the first dose and throughout the study.. Hormone
replacement therapy will not be allowed. After first dosing, acetaminophen (up to 2 g
per 24 hours) may be administered at the discretion of the PI or designee.
20. Has been on a diet incompatible with the on-study diet, in the opinion of the PI,
within the 28 days prior to the first dose and throughout the study.
21. Donation of blood or significant blood loss within 56 days prior to the first dose.
22. Plasma donation within 7 days prior to the first dose.
23. Exposure to more than four new chemical entities within 12 months prior to first
dosing day.
24. The subject has participated in a clinical trial and has received an investigational
product within 30 days, or 5 half-lives of the investigational product (whichever is
longer) of the first dose of study drug in the current study.
25. Any condition or circumstance, in the opinion of the PI, which may make the subject
unlikely to complete the study or comply with study procedures and requirements, or
may pose a risk to the subject's safety.
26. Subject has recent history (within 2 weeks of Day -1) of less than 1 bowel movement
every 2 days.
27. Subject has recent history (within 2 weeks of Day -1) of abnormal bowel movements,
such as diarrhea, loose stools, or constipation.
Stage 1 Only:
28. Is lactose intolerant.
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