| Eligibility |
Inclusion Criteria:
1. Male or female (non-pregnant, non-lactating) aged 18 to 55 years inclusive who will be
contactable and available for the duration of the trial and up to 2 weeks following
the End of Study visit.
2. Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within
the range of 18.5 to 30.0 kg/m2 (Both inclusive). BMI is an estimate of body weight
adjusted for height. It is calculated by dividing the weight in kilograms by the
square of the height in meters.
3. Certified as healthy by a comprehensive clinical assessment (detailed medical history,
complete physical examination and special investigations).
4. Screening vital signs:
Systolic blood pressure (SBP) - 90-140 mmHg, Diastolic blood pressure (DBP) - 60-90
mmHg, Heart rate (HR) 60-90 bpm.
5. QTcF =450 ms, PR interval =220 ms.
6. Female subjects with history of sterility or at least 1 year menopause or use of long
acting non hormonal contraceptive measures (e.g., intrauterine device) and be willing
and able to continue contraception for 90 days after administration of study
treatment.
7. Male subjects must agree to use adequate contraception methods during the study and be
willing and able to continue contraception for 90 days after administration of study
treatment.
8. Completion of the written informed consent process prior to undertaking any study
related procedure.
9. Must be willing and able to communicate and participate in the whole study.
Exclusion Criteria:
1. Haematology, clinical chemistry or urinalysis results at screening that are outside of
clinically acceptable laboratory ranges, and are considered clinically significant by
the Investigator.
2. Participation in any investigational product study within the 12 weeks preceding IMP
administration.
3. History or presence of diagnosed (by an allergist/immunologist) or treated (by a
physician) food or known drug allergies, or history of anaphylaxis or other severe
allergic reactions. Subjects with seasonal allergies/hay fever or allergy to animals
or house dust mite that are untreated and asymptomatic can be enrolled in the study
based on Investigator's discretion.
4. History of convulsion (including intravenous drug or vaccine-induced episodes). A
medical history of a single febrile convulsion during childhood is not an exclusion
criterion.
5. Presence of current or suspected serious chronic diseases such as cardiac or
autoimmune disease (HIV or other immuno-deficiencies), insulin-dependent and
non-insulin dependent diabetes, progressive neurological disease, severe malnutrition,
acute or progressive hepatic disease, acute or progressive renal disease, porphyria,
psoriasis, rheumatoid arthritis, asthma (excluding childhood asthma, or mild asthma
with preventative asthma medication required less than monthly), epilepsy, or
obsessive-compulsive disorder.
6. History of malignancy of any organ system treated or untreated, within 5 years of
screening, regardless of whether there is evidence of local recurrence or metastases.
7. Subjects with history of schizophrenia, bi-polar disease, psychoses, disorders
requiring lithium, attempted or planned suicide, or any other severe (disabling)
chronic psychiatric diagnosis.
8. Subjects who have received psychiatric medications within 1 year prior to enrolment,
or who have been hospitalized within 5 years prior to enrolment for either a
psychiatric illness or due to danger to self or others.
9. History of more than one previous episode of major depression, any previous single
episode of major depression lasting for or requiring treatment for more than 6 months,
or any episode of major depression during the 5 years preceding screening.
10. History of recurrent headache (e.g. tension-type, cluster or migraine) with a
frequency of =2 episodes per month on average and/or severe enough to require medical
therapy, during the 5 years preceding screening.
11. Presence of clinically significant infectious disease or fever (e.g. sublingual
temperature =38.5°C) within the 14 days prior to enrollment.
12. Evidence of acute illness within the 4 weeks prior to screening that the Investigator
deems may compromise subject safety.
13. Significant inter-current disease of any type, in particular liver, renal, cardiac,
pulmonary, neurologic, gastrointestinal, rheumatologic, or autoimmune disease by
history, physical examination, and/or laboratory studies including urinalysis.
14. Subject has a clinically significant disease or any condition or disease that might
affect drug absorption, distribution or excretion (e.g. gastrectomy, diarrhoea).
15. Blood donation of any volume within 1 month before IMP administration, or
participation in any research study involving blood sampling (more than 450 mL/unit of
blood), or blood donation to blood bank during the 12 weeks prior to IMP
administration.
16. Medical requirement for intravenous immunoglobulin or blood transfusions within 3
months prior to enrollment.
17. History or presence of alcohol abuse (alcohol consumption more than 40 g/4 units/4
standard drinks per day), or drug habituation, or any prior intravenous usage of an
illicit substance in past one year.
18. Tobacco use of more than 5 cigarettes or equivalent per day since last one year, and
unable to stop smoking for the duration of the clinical unit confinement.
19. Female subject who is breastfeeding or currently pregnant or found positive on
pregnancy test.
Interfering substances
20. Any vaccination within the last 28 days and planned vaccination till final study
visit.
21. Any corticosteroids, anti-inflammatory drugs (excluding commonly used over-thecounter
anti-inflammatory drugs such as ibuprofen, acetylsalicylic acid, diclofenac),
immunomodulators or anticoagulants within the past 3 months. Any subject currently
receiving or having previously received immunosuppressive therapy (including systemic
steroids, adrenocorticotrophic hormone or inhaled steroids) at a dose or duration
potentially associated with hypothalamic-pituitary-adrenal axis suppression within the
past year.
22. Ingestion of any poppy seeds within the 24 hours prior to screening
23. Consumption of beverages or food containing xanthine bases including Red Bull,
chocolate, coffee etc. from 48 hours prior to enrollment.
24. Unwillingness to abstain from consumption of grapefruit or Seville oranges from 7 days
prior to enrollment until the end of study.
25. Use of prescription drugs (excluding contraceptives) or non-prescription drugs or
herbal supplements (such as St John's Wort), within 14 days or 5 half-lives (whichever
is longer) prior to IMP dosing. Limited use of other non-prescription medications or
dietary supplements, not believed to affect subject safety or the overall results of
the study, may be permitted on a case-by- case basis following approval by the Sponsor
in consultation with the Investigator. Subjects are requested to refrain from taking
non-approved concomitant medications from recruitment until the conclusion of the
study.
26. Any subject who, in the judgment of the Investigator, is likely to be non-compliant
during the study, or is unable to cooperate because of a language problem or poor
mental development.
27. Any subject who is the Principal Investigator or any sub-Investigator, research
assistant, pharmacist, study coordinator, or other staff thereof, directly involved in
conducting the study.
28. Any subject without a good peripheral venous access.
29. Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag),
anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and
2 antibodies (anti-HIV1 and anti-HIV2 Ab).
30. Positive urine drug test.
31. Positive urine alcohol/breath alcohol test.
32. The history or presence of any of the following cardiac conditions: known structural
cardiac abnormalities; family history of long QT syndrome; cardiac syncope or
recurrent, idiopathic syncope; exercise related clinically significant cardiac events.
- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG that may interfere with the interpretation of QTc interval changes.
This includes subjects with any of the following (at screening):
- Sinus node dysfunction.
- Complete bundle branch block.
- Abnormal T wave morphology.
- Any other ECG abnormalities in the standard 12-lead ECG in the opinion of the
Investigator will interfere with the ECG analysis.
|
