| Eligibility |
Inclusion Criteria:
1. Healthy male or female of non-childbearing potential, between =18 years and =65 years
of age, inclusive, at screening.
2. Female subject of non-childbearing potential. For the purposes of this study, this is
defined as the subject being amenorrhoeic for at least 12 consecutive months prior to
study drug administration or at least 6 months post-surgical sterilisation (including
bilateral fallopian tube ligation or bilateral oophorectomy with or without
hysterectomy).
3. Female subject with a negative pregnancy test at screening and admission.
4. Male subject (and partner of childbearing potential) willing to use a highly effective
method of contraception or 2 effective methods of contraception, if applicable (unless
anatomically sterile or where abstaining from sexual intercourse is in line with the
preferred and usual lifestyle of the subject) from first dose until 3 months after
last dose of the investigation medicinal product (IMP).
5. Male subjects (including men who have had vasectomies) with a pregnant partner must
agree to use a condom from first dose until at least 3 months (90 days) after last
dose of IMP.
6. Male subjects must be willing to not donate sperm until 3 months (90 days) following
last dose of IMP.
7. Subject with a body mass index (BMI) of >18.5 and <30 kg/m2 and body weight =50.0 kg
for males and =45.0 kg for females (BMI = body weight (kg) / [height (m)]2), at
screening.
8. Healthy as defined by:
1. Absence of clinically significant illness and surgery within 4 weeks prior to
dosing. Subjects vomiting within 24 hours (h) pre-dose will be carefully
evaluated for upcoming illness/disease. Inclusion pre-dosing is at the discretion
of the PI.
2. Absence of clinically significant history of neurological, endocrinal,
cardiovascular, pulmonary, haematological, immunologic, psychiatric,
gastrointestinal, renal, hepatic and metabolic disease.
9. Continuous non-smoker who has not used tobacco or nicotine-containing products for at
least 3 months prior to Screening and throughout the study, or users of cigarette
replacements (i.e., e-cigarettes, nicotine patches or gums).
10. No clinically significant history of previous allergy / sensitivity to PBI-4050 or any
of the excipients contained within the IMP(s).
11. No clinically significant abnormal test results for serum biochemistry, haematology,
coagulation, and/or urine analyses within 28 days before the first dose administration
of the IMP.
12. Subject with a negative urinary drugs of abuse (DOA) screen (including cotinine) and
alcohol breath test results, determined within 28 days before the first dose
administration of the IMP (N.B.: A positive alcohol and/or cotinine test result may be
repeated at the Investigator's discretion).
13. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen
(HBsAg) and hepatitis C virus antibody (HCV Ab) test results at screening.
14. Subject must be available to complete the study (including all follow up visits).
15. Subject must satisfy an Investigator about his/her fitness to participate in the
study.
16. Subject must provide written informed consent to participate in the study.
Exclusion Criteria:
1. A clinically significant abnormality or abnormal laboratory test results found during
medical screening or a positive test for hepatitis B surface antigen (HBsAg),
hepatitis C virus (HCV), or human immunodeficiency virus (HIV) found during medical
screening.
2. Evidence of clinically significant hepatic or renal impairment including alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) above 1.2 x the upper
limit of normal (ULN), direct bilirubin above 1.2 x ULN (total bilirubin accepted up
to 2 x ULN if direct bilirubin is within normal limits), or creatinine is above ULN.
3. An estimated creatinine clearance as assessed by the Cockroft-Gault equation <60
mL/min at screening or admission.
4. Positive urine drug screen (including cotinine) or alcohol breath test at Screening or
admission.
5. History of significant allergic reactions (e.g. anaphylactic reaction and angioedema)
to any drug.
6. Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days
prior to the first study drug administration.
7. Female subject with a positive pregnancy test at screening or admission.
8. Clinically significant electrocardiogram (ECG) abnormalities at screening or
admission, including PR > 220ms QTcF > 450ms.
9. Supine / Semi-supine systolic blood pressure lower than 90 or over 140 mmHg, diastolic
blood pressure lower than 50 or over 90 mmHg at screening.
10. Heart rate less than 40 or over 100 bpm at screening or admission.
11. A clinically significant history of drug or alcohol abuse [defined as the consumption
of more than 14 units for male and female subjects) of alcohol a week], including use
of soft drugs (such as marijuana) or hard drugs (such as cocaine, phencyclidine [PCP],
crack, opioid derivatives including heroin and amphetamine derivatives) within the
past year.
12. Participation in a New Chemical Entity (NCE) clinical study within the previous 3
months or a marketed drug clinical study within the 30 days before the first dose of
IMP, or administration of a biological product in the context of a clinical research
study within the 90 days before the first dose of IMP or concomitant participation in
an investigational study involving no drug or device administration. (Washout period
between studies is defined as the period of time elapsed between the last dose of the
previous study and the first dose of the next study).
13. Use of medication other than topical products without significant systemic absorption,
unless in the opinion of the Investigator and Sponsor's Responsible Physician the
medication will not interfere with the study procedures or compromise subject safety:
1. Prescription medication within 14 days prior to dosing;
2. Non-prescription medication including vitamins, herbal and dietary supplements
within 7 days or 5 half-lives (whichever is longer), and ibuprofen within 48 h
prior to the first dose of IMP,
3. A depot injection or an implant of any drug within 3 months before the first dose
of IMP.
14. Donation of 450 mL or more blood within the 3 months before the first dose of IMP.
15. Donation of plasma within 7 days prior to dosing.
16. Receipt of blood products within 2 months prior to admission.
17. Haemoglobin <130 g/L (males) and <115 g/L (females) and haematocrit <0.36 L/L (males)
and <0.32 L/L (females) at screening or admission.
18. Breast feeding or lactating female subject.
19. A clinically significant history of gastrointestinal disorder likely to influence IMP
absorption.
20. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or
metabolic dysfunction.
21. Inability to communicate well with the Investigators (i.e., language problem, poor
mental development or impaired cerebral function).
22. Subjects with any special food restrictions that would hinder ability to consume the
high fat breakfast provided during the study; e.g. vegetarian, lactose intolerance,
vegan, low-fat, low sodium, and/or restrictions for medical, religious, social or
cultural reasons, etc).
23. Any reason which, in the opinion of the PI, would prevent the subject from
participating in the study.
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