| Eligibility |
Inclusion Criteria:
1. Healthy males or females of any race, between 18 and 55 years of age, inclusive.
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive, with a body weight of at least
50.0 kg.
3. In good physical and mental health, including no clinically significant findings from
medical history, physical examination, psychiatric examination, 12 lead ECG, vital
signs measurements, and clinical laboratory evaluations (congenital nonhemolytic
hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct
bilirubin] is not acceptable) at screening or check in as assessed by the investigator
(or designee).
4. Females who are not pregnant or lactating, and females of childbearing potential and
males will agree to use contraception.
5. Has clinical laboratory test results within the reference ranges of the testing
laboratory, with the exception of results outside the reference ranges that are deemed
not clinically significant by the Investigator (or designee) at screening and
check-in.
6. Has supine blood pressure and pulse rate within the following ranges after 5 minutes
rest: systolic blood pressure 90 to 140 mmHg, diastolic blood pressure 40 to 90 mmHg,
and pulse rate 45 to 90 bpm.
7. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
Exclusion Criteria:
1. Past or current history of any mental, behavioural, or neurodevelopmental disorder as
defined by the tenth revision of the International Classification of Diseases
(ICD-10)16 including, but not limited to, diagnoses of: organic, including
symptomatic, mental disorders (F00-F09); mental and behavioural disorders due to
psychoactive substance use (F10-F19); schizophrenia, schizotypal, and delusional
disorders (F20-F29); mood [affective] disorders (F30-F39); neurotic, stress-related,
and somatoform disorders (F40-F48); disorders of adult personality and behaviour
(F60-F69).
2. Significant history or clinical manifestation of any metabolic, allergic,
dermatological, hepatic, renal, haematological, pulmonary, gastrointestinal,
neurological, respiratory, or endocrine disorder, as determined by the Investigator
(or designee).
3. Active or history of cardiovascular or cerebrovascular disease, including
hypertension, angina, ischaemic heart disease, transient ischaemic attacks, bundle
branch block, evidence of myocardial ischaemia, stroke, and peripheral arterial
disease sufficient to cause symptoms and/or require therapy to maintain stable status.
4. History of significant hypersensitivity, intolerance, or allergy to any drug compound,
food, or other substance, unless approved by the investigator (or designee).
5. 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 definitely treated with standard of care).
6. Active infection (eg, sepsis, pneumonia, abscess) or a serious infection (eg,
resulting in hospitalisation or requiring parenteral antibiotic treatment) within 6
weeks prior to dosing.
7. 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).
8. Any of the following at screening and/or predose:
1. QT interval corrected for heart rate using Fridericia's method (QTcF) >450 ms
confirmed by repeat measurement
2. QRS duration >110 ms confirmed by repeat measurement
3. PR interval >220 ms confirmed by repeat measurement
4. findings which would make QTc measurements difficult or QTc data uninterpretable
5. history of additional risk factors for torsades de pointe (eg, heart failure,
hypokalemia, family history of long QT syndrome).
9. History of alcoholism or drug/chemical abuse.
10. Alcohol consumption of >14 units (females) and >21 units (males) per week. One unit of
alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill
(25 mL) of spirits.
11. Positive alcohol breath test result or positive urine drug screen, including cotinine
(confirmed by repeat) at screening or check in.
12. Positive hepatitis panel and/or positive human immunodeficiency virus test.
13. Any of the following haematology values at screening or check-in, as confirmed by 1
repeat if necessary:
1. haemoglobin <11 g/dL for females, and <12 g/dL for males
2. absolute neutrophil count <1.5 × 109/L (<1500/µL).
14. Renal or liver impairment at screening or check-in defined as, confirmed by 1 repeat
if necessary:
1. serum creatinine =135 µmol/L
2. ALT and/or AST =2 × ULN
3. ALP and/or total bilirubin >1.5 × ULN (an isolated total bilirubin >1.5 × ULN is
acceptable if total bilirubin is fractionated and direct bilirubin is <35%).
15. 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.
16. Use or intend 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.
17. Use or intend to use any prescription medications/products within 14 days or 5 half
lives of the medication/product, whichever is longer, prior to check-in (hormone
replacement therapy, oral, implantable, transdermal, injectable, or intrauterine
contraceptives are acceptable).
18. Use or intend to use any nonprescription medications/products including vitamins,
minerals, and phytotherapeutic/herbal/plant derived preparations within 14 days prior
to check in.
19. Use or intend to use slow release medications/products considered to still be active
within 14 days prior to check in.
20. Received live attenuated vaccination within 6 weeks prior to screening or intends to
receive such a vaccination during the study.
21. 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 6 months prior to check-in and the inability to abstain from
nicotine-containing products until the follow-up visit.
22. Receipt of blood products within 2 months prior to check in.
23. 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.
24. Poor peripheral venous access.
25. Consumption of caffeine-containing foods and beverages within 72 hours of screening or
is unable to abstain from caffeine-containing foods and beverages from 7 days prior to
check in until discharge.
26. Consumption of any foods or beverages which alter CYP1A2 activity, eg, barbecued food
or cruciferous vegetables, such as broccoli and cauliflower, within 14 days prior to
check-in (a list of prohibited foods will be provided to subjects).
27. Consumption of any foods or beverages containing Seville-type oranges, grapefruit, or
poppy seeds within 7 days prior to check-in.
28. Have previously completed or withdrawn from this study, and have previously received
the IMP.
29. Subjects who, in the opinion of the investigator (or designee; including input from
subjects' general practitioner, as applicable), should not participate in this study.
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