| Eligibility |
Inclusion Criteria
1. Written informed consent must be obtained before any assessment is performed.
2. Healthy male and female subjects age 18 to 55 years of age included.
3. Subjects must weigh at least 50 kg to participate in the study, and must have a body
mass index (BMI) within the range of 18-32 kg/m2 inclusive.
4. At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will
be assessed in the sitting position after the subject has rested for at least three
minutes, and again (when required) after three minutes in the standing position.
Sitting vital signs should be within the normal ranges.
5. Women of child-bearing potential (WOCBP), defined as all women physiologically capable
of becoming pregnant must use highly effective methods of contraception during
intercourse while taking drug and for 30 days after stopping study medication; and
sexually active males must use a condom, during intercourse while taking drug and for
30 days after stopping study medication.
6. Able to communicate well with the investigator, to understand and comply with the
requirements of the study.
Exclusion Criteria
Healthy subjects fulfilling any of the following criteria are not eligible for inclusion in
this study:
1. Any surgical or medical condition which might significantly alter the absorption,
distribution, metabolism, or excretion of drugs, or which may jeopardize the subject
in case of participation in the study.
2. Hemoglobin levels below the lower limit of normal (LLN) as set by the laboratory.
3. An elevated C-reactive protein (CRP) outside of the normal reference range and has
clinical significance, or above 10 mg/L.
4. A positive anti-nuclear antibody (ANA) above 1:160 titer.
5. A positive Tuberculosis test.
6. A history of clinically significant ECG abnormalities, or any abnormalities defined in
protocol.
7. History of immunodeficiency diseases, including a positive test for HIV antibody.
8. Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
9. Infections requiring parenteral antibiotics within the 6 months prior to Screening.
10. History of any venous thromboembolism, TIA, intracranial hemorrhage, neoplasm,
arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or
screening blood tests that indicate altered coagulability (platelet count, APTT, PT,
etc.).
11. History of significant cardiovascular, respiratory, renal, neurological disease.
12. Significant illness which has not resolved within two (2) weeks prior to initial
dosing.
13. History of malignancy of any organ system (other than localized basal cell carcinoma
of the skin), treated or untreated, within the past 5 years, regardless of whether
there is evidence of local recurrence or metastases.
14. Recent (within the last three years) and/or recurrent history of autonomic dysfunction
(e.g., recurrent episodes of fainting, palpitations, etc.).
15. Known family history or known presence of long QT syndrome, or concomitant use of
agents known to prolong the QT interval unless they can be permanently discontinued
for the duration of study.
16. History of hypersensitivity to any of the study treatments or excipients (e.g.,
lactose monohydrate) or to drugs of similar chemical classes; and history of
anaphylaxis or other significant allergy in the opinion of the Investigator.
17. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial
dosing, or longer if required by local regulation.
18. Plasma donation (>400 mL) within 14 days prior to first dosing.
19. Use of any prescription drugs, herbal supplements (including Silybum marianum and
Valeriana officinalis), within two weeks prior to initial dosing, and/or over-the-
counter (OTC) medication, dietary supplements (vitamins included) within one weeks
prior to initial dosing.
20. Smokers of more than two per week. Urine cotinine levels will be measured during
screening, and urine cotinine = 500 ng/ml will exclude a subject.
21. History of drug abuse or unhealthy alcohol use within the 12 months prior to dosing,
or evidence of such abuse as indicated by the laboratory assays conducted during
screening.
22. History of recreational cannabis use within four weeks prior to dosing, or evidence of
such use as indicated by the laboratory assays conducted during screening.
23. Participant is unwilling to refrain from strenuous exercise (including weightlifting)
from 7 days prior to admission to the site until completion of the final Follow-up
visit.
24. With a plan to receive vaccination with a live vaccine within 4 weeks prior to the
first dosing or within 4 weeks of the last dosing; With a plan to receive COVID-19
vaccination within 2 weeks prior to the first dosing or within 1 week of the last
dosing.
25. Exposure to any significantly immune suppressing drug (including experimental
therapies as part of a clinical trial) within the 4 months prior to screening or 5
half-lives, whichever is longer.
26. Use of other investigational drugs at the time of enrollment, or within 5 half-lives
of enrollment, or within 30 days, or twice the duration of the biological effect of
the investigational product, whichever is longer; or longer if required by local
regulations.
27. Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.
28. (Part ? only) Score 'yes' on item 4 or item 5 of the Suicidal Ideation section of the
C-SSRS, if this ideation occurred in the past 6 months, or 'yes' on any item of the
Suicidal Behavior section, except for the 'Non-Suicidal Self-Injurious Behavior' (item
also included in the Suicidal Behavior section), if this behavior occurred in the past
2 years. Or history of drug abuse or mental disease.
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