A DDI Study to Evaluate the Effects of Itraconazole and Fluoxetine on AK0529 in Healthy Volunteers

Exclusion Criteria21

• Has a QTcF interval > 450 msec.
• Has a history or presence of prolonged QTc or family history of long QT syndrome.
• Has any finding that, in the opinion of the investigator, would compromise the subject’s ability to fulfill the protocol visit schedule or study requirements.
• Has current evidence, or history of any clinically significant medical or psychiatric condition or observed abnormality that could potentially compromise subject safety or evaluation of PK parameters.
• If female, is currently pregnant or breastfeeding.
• Has a history of, or current infection with, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, or has a history of liver disease, including unexplained fluctuations in liver function tests.
• Has used CYP3A4 or CYP2D6 inhibitors or inducers or P-gp inhibitors within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or anticipates a need to use any CYP3A4 or CYP2D6 inhibitors or inducers, or P-gp inhibitors during the study period.
• Use of prescription or non-prescription drugs, herbal products, nutritional supplements or ‘alternative’ medication or remedies within 14 days or 5 half-lives (whichever is the longer) prior to the first dose of study drug.
• Intake of grapefruit, grapefruit juice or grapefruit-related citrus fruits within 7 days prior to the first dose of the study medication.
• Has a known intolerance or allergy to AK0529, itraconazole, fluoxetine or related compounds.
• Previous intolerance to SSRI or SNRI drugs.
• Has a history or current presence of psychiatric symptoms including anxiety, mood disturbance, suicidal ideation or self-harming behaviour.
• Has a history of seizure, except for simple, febrile convulsion as a child.
• History of regular alcohol consumption exceeding a weekly intake of more than 21 units for males and more than 14 units for females within 6 months of screening.
• Is a smoker, or has ceased using tobacco-containing or nicotine-containing products within 3 months of screening, not including light or social smoking not exceeding the equivalent of 5 cigarettes per week, and/or has a positive cotinine test at screening or Day -1.
• Excessive consumption of beverages containing xanthine bases.
• Has used alcohol-, caffeine- or xanthine-containing products within 72 hours prior to admission on Day -1.
• Has a positive urine toxicological screen for cotinine (or saliva test), benzodiazepines, opioids amphetamine/methamphetamine, cannabinoids or cocaine at screening or Day -1.
• Has a positive alcohol breath test at screening or Day -1.
• Has donated blood of more than 500 ml within 4 weeks prior to screening.
• Participation in any investigational product study within 12 weeks or five half-lives (whichever is longer) prior to the first dose of the study medication.