An Open-Label, Crossover, Relative Bioavailability Study Comparing Tablet and Capsule Formulations of SKY-0515 in Healthy Volunteers

Exclusion Criteria34

• Volunteers will be excluded from the study if they meet any of the following criteria:
• Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
• Suffers from frequent or recurrent infections (defined as greater than or equal to 3 recurrent or separate occurrences in the 12 months preceding first study drug administration or 2 recurrent or separate occurrences in the 6 months preceding first study drug administration).
• Active malignancy and/or any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma or low grade cervical intraepithelial neoplasia).
• Evidence of clinically relevant immunosuppression, including (but not limited to), immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients.
• Presence or history of cardiovascular disease (including unstable angina, myocardial infarction, chronic heart failure).
• History of any CS disorder, including haematologic, pulmonary, hepatic, renal, GI, connective tissue disease, uncontrolled endocrine/metabolic, neurologic (including seizures, strokes, brain tumours), and psychiatric diseases, or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug.
• Prescence or having sequelae of GI, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (prior gall bladder and/or appendix removal is not exclusionary if the procedure was undertaken greater than or equal to 3 months prior to study drug administration; if less than 3 months, history of such procedures may still be considered not exclusionary if it is deemed appropriate by the PI or delegate).
• History of surgery or hospitalisation within 12 weeks prior to screening, or surgery planned during the study.
• Lack of suitable veins for multiple venipunctures/cannulations as assessed by the PI or delegate at screening or Day -1.
• Volunteer has significant (greater than 10%) weight gain or loss between screening and Day -1.
• Volunteer has donated blood/blood products or experienced significant blood loss within 3 months prior to the first dose administration.
• Laboratory results at screening that indicate inadequate renal function (estimated creatinine clearance of less than 60 mL/min calculated by the Cockcroft and Gault formula).
• Liver function test results elevated more than 1.5-fold above the Upper limit of normal (ULN) for gamma glutamyl transferase (GGT), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
• Liver function tests outside the normal range for bilirubin (more than 1.5-fold above the ULN for total bilirubin).
• Any clinically relevant laboratory finding or medical condition that could place the participant at risk for participation in the study, in the opinion of the PI.
• Use of any vaccinations within 14 days (within 4 weeks for live virus vaccines) prior to the first study drug administration.
• Use of any prescription medication or over-the-counter medication/supplements/herbal medications within 7 days prior to the first dose of study drug. Exceptions include:
• a. Contraception,
• b. Antihistamines,
• c. Occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days) or ibuprofen (doses of 400 mg up to every 6 hours or 1.2 g per day maximum for no more than 3 consecutive days),
• d. Low doses of multivitamins,
• Use of St. John’s Wort (hypericin) within 30 days prior to first dose of study drug.
• Concurrent enrolment in another clinical study, or participation in another clinical study within 30 days or 5 half-lives of the IP (whichever is longer) prior to screening.
• Regular consumption of greater than 10 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], 30 mL spirit [40% Alc/Vol]), and/or volunteer is unwilling to abstain from alcohol while confined to the study site.
• Positive alcohol breath test at screening or upon admission to the study site on Day -1.
• Positive urine drugs of abuse test at screening or upon admission to the study site on Day -1.
• Volunteer has a positive cotinine test upon admission to the study site on Day -1.
• Volunteer smokes 10 or more cigarettes or equivalent (see note below) per week, and/or volunteer is unwilling to abstain from smoking for at least 48 hours prior to check-in (Day -1) and while confined to the study site.
• Volunteer is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
• Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the volunteers inclusion in the clinical study or evaluation of the clinical study results.
• Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
• Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.