An Open-label, 2 Part, Study to Assess the Pharmacokinetics of a Spray Dried Dispersion Formulation of Radiprodil Under Fasted and Fed Conditions in Healthy Adult Subjects: Part A

Exclusion Criteria27

• Known hypersensitivity to the study drug or any of the study drug ingredients.
• History of suicide attempts or deliberate self-harm, or a score of 4 or 5 on ideation or any suicidal behaviour on the Columbia-Suicide Severity Rating Scale (C SSRS).
• History of anaphylaxis or other significant allergy (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic seasonal allergies at time of dosing on Day 1) 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, determined by the PI (or delegate) to be clinically relevant.
• History of surgery within 3 months prior to Day 1 as determined by the PI (or delegate) to be clinically relevant, or surgery planned during the study.
• 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 more than 1.5-fold above the ULN for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST 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) less than 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN.
• 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, cotinine test or alcohol breath test results at the screening visit and/or on admission to the CRU on Day 1.
• 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]).
• Routine consumption of an average of more than five (5) 240 mL servings of coffee or other caffeinated beverages per day.
• Use of marijuana (including prescribed marijuana) within 30 days of Day -1.
• Use of tobacco-containing products and nicotine or nicotine containing products in the 2 months prior to Day 1.
• Females who are breastfeeding or planning to breastfeed.
• Unable to swallow oral medication.
• Use of any prescription or over-the-counter medication (including herbal products, diet aids, vitamins, and hormone supplements) within 14 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug, except use of contraceptives. Up to 2 grams per day of acetaminophen will be allowed at the discretion of the Investigator.
• Acute illness within 14 days of study Day 1.
• Use of any vaccinations within 7 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.
• Dosed in another clinical trial within 28 days prior to radiprodil dosing. Participants enrolled in Part A of the RAD-GRIN-503 study are permitted to participate in Part B if there is at least 7 days between the last dose administered in Part A and the first dose administration in Part B.
• Consumption of the following prior to dosing period:
• a. Alcohol 48 hours prior to dosing.
• b. Grapefruit (or pomelo or star fruit), Seville oranges, Seville orange marmalade, poppy seeds or other products containing these fruits within 10 days prior to dosing.
• c. Caffeine and/or xanthine-containing products (e.g., tea, coffee) within 24 hours prior to dosing.
• 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.