A Phase 1, Randomised, Open-Label, Three-way Crossover Comparative Pharmacokinetic Study of Capsule and Tablet Dosage Forms of EMA401 Sodium Salt When Administered Orally in Healthy Adult Males

Exclusion Criteria21

• Have received or is anticipated to receive a new prescription systemic or topical medication within 14 days prior to the start of dosing or an over-the-counter medicine 48 hours prior to the start of dosing;
• Subjects receiving medications (within the last 7 days prior to Screening) that have the potential to prolong the QT interval or who may require such medications during the course of the study;
• Any condition that would interfere with drug absorption (e.g. chronic diarrhoea);
• Subjects with abnormal laboratory test results deemed clinically significant by the Medical Officer (Principal Investigator or medically qualified nominee) within 21 days before enrollment, including anaemia (hemoglobin less than 12.0 g/decilitre), total cholesterol (greater than 5.5 mmol/L which is equivalent to 212 mg/dL), neutropenia, thrombocytopenia, elevated liver function test results [alanine aminotransferase (ALT) and aspartate transaminase (AST)] above the upper limit of normal and, serum potassium or magnesium concentrations outside of the normal range;
• Subjects with calcium concentrations greater than 10% outside of the normal range (this variation is to allow for artifactual results due to variations in sampling conditions);
• Males known to have experienced elevated liver enzymes or altered white cell counts in any previous clinical study;
• Evidence of significant renal insufficiency, as indicated by an estimated creatinine clearance using the Cockcroft-Gault formula of less than 75 mL/minute at Screening;
• As a result of medical review, physical examination (including height and weight) or Screening investigations, the Medical Officer considers the subject unfit for the study;
• Positive urine drug test or alcohol breath test;
• Use of macrolide antibiotics (e.g. erythromycin), azole antifungal agents (e.g. ketoconazole) within 30 days of study dosing;
• History or clinical evidence of oral, cardiovascular, cerebrovascular, haematological, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurological, psychiatric or skin disorder;
• History of epilepsy;
• History or clinical evidence of significant cardiovascular disease including subjects with complete left bundle branch block (LBBB) ischaemic heart disease, peripheral vascular disease, uncontrolled hypertension and history of, or risk factors for, cardiac ventricular arrhythmias (e.g. personal history or family history of syncope, long QT syndrome or sudden death);
• Acute therapy for a serious infection within 30 days of study entry;
• History of significant drug allergies or significant allergic reaction or currently suffers from clinically significant systemic allergic disease;
• Positive Screening test for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV) or human immunodeficiency virus (HIV);
• Have participated in a clinical trial or have received an experimental therapy within 30 days or 10 half-lives of the drug, whichever is the longer, prior to dosing;
• Receipt of blood or blood products, or loss or donation of 450 mL or more of blood within 90 days before the first dose administration;
• Males who regularly drink more than four (4) units of alcohol daily (1 unit = 300 mL beer, 1 glass of wine, 1 measure spirit);
• Males who are unwilling to abide by study restrictions to be listed in the full protocol. These will include dietary restrictions (certain citrus fruits restriction 14 days prior to admission, caffeine/related products and alcohol restrictions 48 hours prior to admission), willingness to fast for a minimum 8 hours prior to each dose until 2 hours post-dose, fluid restriction (except for water given with dosing, no fluid intake from at least 1 hour prior to each dose until 1 hour post-dose);
• Any subject who has previously enrolled in this or any clinical trial of EMA401.