A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered BT-409 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of BT-409 in Healthy Volunteers.

Exclusion Criteria25

• Volunteers will be excluded from the study if they meet any of the following criteria:
• Known hypersensitivity to the study drug or any of the study drug ingredients.
• History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, within the past 3 months determined by the PI (or delegate) to be clinically relevant.
• History of surgery or hospitalisation within 3 months prior to screening, or surgery planned during the study.
• Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
• Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Liver function test results elevated greater than 1.5-fold above the upper limit for gamma glutamyl transferase (GGT), total bilirubin, ALP, AST or ALT. Participants with elevated GGT, ALP, AST and/or ALT above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
• Estimated creatinine clearance (CrCl) lesser than 90 mL/min using the Cockcroft-Gault formula or serum creatinine greater than 1.2-fold above the upper limit.
• A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
• Positive drugs of abuse test, carbon monoxide breath test or alcohol breath test results at the screening visit and/or on admission to the study site on Day 1 (Part A) or Day -2 (Part B).
• Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, 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], or 30 mL spirit [40% Alc/Vol]) within 3 months prior to screening.
• Females who are breastfeeding or planning to breastfeed during the study.
• Unable to swallow oral medication.
• Use of any prescription or over-the-counter medication (including herbal products, diet aids, vitamins, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug, except use of contraceptives, the use of paracetamol (up to 2 g per day) for no more than 3 consecutive days and the use of ibuprofen (up to 1.2 g per day) for no more than 3 consecutive days.
• In addition, participants must not take systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) within 28 days or 5 half-lives of individual agent (whichever is longer) prior to dosing and during the study.
• Use of or plans to use agents (e.g., grapefruit and grapefruit products) that have clinically significant interaction with CYP3A4 or the use of any medications that could have a significantly impact on organ function (e.g., barbiturates, omeprazole, cimetidine) during the study or within 5 half-lives of individual agent or within 7 days (whichever is longer) prior to dosing.
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medication within 10 days prior to first dose of study drug.
• Use of any vaccinations within 30 days prior to screening.
• Donation of blood or plasma within 30 days prior to first dose of study drug, or loss of whole blood of more than 500 mL within 30 days prior to first dose of study drug, or receipt of a blood transfusion within 1 year of the first dose of study drug.
• Participation in any clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening.
• 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.
• Any condition or findings, such as signs of increased intracranial pressure, skin infection at puncture site, spinal infection, severe bleeding/clotting disorders, brain mass, recent neurosurgery, spinal disease, where a lumbar puncture is contraindicated or that may make CSF collection difficult.