A Study in Healthy Males and Females to Test How Different Doses of OPC-224333 are Tolerated (Arm 1)

Exclusion Criteria26

• assessed:
• Clinically significant abnormality in past medical history or at the screening physical examination (including but not limited to clinical laboratory tests), that in the investigator’s or sponsor’s opinion may place the subject at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of the IMP. This includes, but is not limited to, history of or concurrent cardiac, hepatic (liver function tests > 1.5 × upper limit of normal [ULN] at screening/baseline), renal (estimated glomerular filtration rate per chronic kidney disease epidemiology formula <60 mL/min), neurologic, endocrine,
• gastrointestinal, respiratory, hematologic, and immunologic disease.
• History of drug and/or alcohol abuse within 2 years prior to screening.
• History of or current hepatitis or acquired immunodeficiency syndrome or carriers
• of hepatitis B surface antigen (HBsAg), hepatitis C antibodies (anti-HCV), and/or human immunodeficiency virus (HIV) antibodies. Exceptions are permitted for subjects with a prior history of infection with hepatitis A who have fully recovered and are experiencing no liver sequelae, or with hepatitis C who have been adequately treated to be considered cured with no liver sequelae.
• History of any medically significant allergy.
• A positive urine or breath alcohol test and/or a positive urine drug screen for substance of abuse at screening or upon check-in to the trial site.
• Subject having taken an investigational drug within 30 days preceding screening or a biological investigational drug within 30 days or 5 half-lives (whichever is longer) preceding screening,
• Any history of significant bleeding or hemorrhagic tendencies.
• Any history of difficulty in donating blood.
• Donation of blood or plasma within 30 days prior to dosing.
• Subjects without a permanent physical residence.
• Consumption of alcohol and/or food and beverages containing methylxanthines (caffeinated coffee, caffeinated tea, caffeinated soda, and chocolate), pomelo, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 3 days prior to dosing.
• Use of prescription drugs, over-the-counter drugs, herbal medication, or vitamin
• supplements within 14 days or 5 half-lives, whichever is longer, prior to dosing and antibiotics within 30 days prior to dosing. The sponsor may allow exceptions only if the medication’s administration is deemed unlikely to impact the pharmacokinetic (PK) results.
• Exposure to any substances known to stimulate hepatic microsomal enzymes
• within 30 days prior to screening (eg, occupational exposure to pesticides, organic solvents).
• Use of tobacco products or daily exposure to second-hand smoke within 2 months
• prior to screening, which result in urine cotinine concentrations > 500 ng/mL, or serum cotinine concentrations > 20 ng/mL at screening or at check-in to the trial site.
• Uncontrolled hypertension, defined as supine systolic blood pressure = greater than or equal to 140 mmHg and/or supine diastolic blood pressure = greater than or equal to 90 mmHg at screening or check-in, or symptomatic hypotension or orthostatic hypotension, which is defined as a decrease of = greater than or equal to 20 mmHg in systolic blood pressure and/or a decrease of = greater than or equal to 10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the previous supine blood pressure, at screening or check-in.
• Supine heart rate (HR), after resting for at least 3 minutes, outside the range of 45 to 100 beats per minute. The sponsor may allow exceptions if the results are not considered to be clinically significant; however, this will need to be approved by the medical monitor. Note: If the first HR measurement is abnormal, it can be repeated at the investigator’s discretion, in which case a third (confirmatory) measurement may also be required.
• Clinically relevant changes on ECG such as atrioventricular block (ie, PR > 220 msec), prolongation of the QRS complex over 120 msec, or a QT interval corrected for heart rate using Fridericia’s formula (QTcF) = greater than or equal to 450 msec in males or = greater than or equal to 470 msec in females.
• Sexually active males or females of childbearing potential (FOCBP), or their partners, who do not agree to practice 2 different approved methods of birth control or remain fully abstinent (periodic abstinence or withdrawal are not acceptable methods of contraception) during the trial and for 90 days after the last dose of IMP. If employing birth control, 2 of the following methods must be used: vasectomy, tubal ligation, nonhormonal intrauterine device, condom or occlusive cap (vaginal diaphragm or cervical/vault cap).
• History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
• Any subject who, in the opinion of the investigator, should not participate in the trial.