A Phase 1 Study to Evaluate a Tablet Formulation of PBT434 in Healthy Volunteers

Exclusion Criteria29

• Women who are pregnant or breastfeeding
• History or presence of malignancy, with the exception of adequately treated localized skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix, which are allowed
• Evidence of any clinically relevant medical illness, including cardiovascular, hematological, gastrointestinal, hepatic, renal, rheumatologic, endocrine, pulmonary, neurologic, psychiatric or skin disorders
• Clinically significant surgical procedure within 3 months prior to screening or anticipated surgery during the study
• History of epilepsy (other than febrile seizures during childhood)
• History of head trauma with loss of consciousness, amnesia or skull fracture
• Currently suffers from clinically significant systemic allergic disease or has a history of significant drug allergies including a history of anaphylactic reaction; allergic reaction due to any drug which led to significant morbidity
• Unable to swallow study medication
• History or presence of cardiac arrhythmia or congenital long QT syndrome
• QTcF >450 msec for men or >470 msec for women on screening or baseline ECG
• Use of any tobacco or nicotine containing products (including social use) in the 3 months prior to dosing or a positive urine cotinine test prior to dosing
• Regular alcohol consumption >2 units/day (1 unit = 250 mL of beer, 100 mL of wine, or 30 mL of distilled spirits or liquor) or alcohol consumption within 24 hours prior to dosing until study completion
• Positive urine drug or alcohol breathalyzer test prior to study entry (during screening or Day -1) or during the study, or history of alcohol or drug abuse in the 12 months prior to dosing
• Evidence of renal insufficiency, as indicated by an estimated creatinine clearance <90 mL/min using the Cockcroft-Gault equation
• Any of the following abnormalities in liver enzymes at Screening or Baseline:
• a. Aspartate transaminase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN)
• b. Alkaline phosphatase (ALP) or total bilirubin (TBil) >2 times the ULN
• Hemoglobin value less than the lower limit of normal
• Positive results of serology screening for hepatitis B (hepatitis B surface antigen [HBsAg]), hepatitis C (anti-hepatitis C virus [HCV] antibodies) or HIV (HIV antibodies type 1 and 2)
• Any acute illness, clinically significant infection or clinically significant abnormal laboratory result within 28 days prior to dosing
• Use of any prescription medication within 28 days prior to dosing
• Use of any non-prescription medication (including non-steroidal anti-inflammatory drugs), herbal remedy (including St. John’s Wort) or vitamin supplement, within 14 days prior to dosing and throughout the study
• Note: Approved doses of paracetamol (acetaminophen, up to a maximum of 2,000 mg/day) may be permitted during Screening and while on study at the investigator’s discretion.
• Use of an investigational drug or device within 28 days or 10 half-lives of the drug, whichever is longer, prior to start of dosing (or within 6 months prior to Day -1 if investigational drug was a biologic)
• Clinically significant blood loss or blood or plasma donation >550 mL within 90 days prior to start of dosing
• As a result of history and physical examination, the Investigator considers the subject unfit for the study
• Any condition (e.g., chronic diarrhea, inflammatory bowel disease) or prior surgery (including surgery of the gastrointestinal and/or biliary tract) that could interfere with drug absorption, distribution, metabolism, or excretion of the IP
• The subject has previously participated in a clinical trial of PBT434 within 28 days prior to dosing or experienced a clinically significant adverse event in a previous clinical trial of PBT434
• Note: Subjects who have previously participated in a clinical trial of PBT434 may be enrolled only if approved by the Medical Monitor