A Study Evaluating the of OPC-34712 in Subjects With Normal Hepatic Function and Hepatically Impaired Subjects

This is an interventional treatment trial for Schizophrenia Read More

Inclusion Criteria:

• Males and females of non-childbearing potential ≥ 18 years of age
• Body weight within ± 30% of ideal body weight as defined in the 1983 Metropolitan Height and Weight Tables. Minimum body weight no less than 50 kg.
• Able to provide written, informed consent.
• Male and female subjects who are surgically sterile; female subjects who have been postmenopausal for at least 12 consecutive months; or male subjects who agree to remain abstinent or to practice double-barrier forms of birth control and refrain from sperm donation from Screening through 90 days from the last dose of study medication.

Inclusion Criteria for Hepatically Impaired Subjects Only:

• Hepatically impaired subjects with creatinine clearance (CLcr) > 30 mL/min.
• Subjects with hepatic impairment should have relatively stable hepatic function for the duration of the study, and otherwise be in generally good health.
• A clinical diagnosis of hepatic cirrhosis based on biopsy and/or clinical criteria.
• Child-Pugh Class A (mild), B (moderate), or C (severe)
• Hepatically impaired subjects may be taking medications, which in the opinion of the clinical investigator and sponsor, are believed to be therapeutic for the subjects.
• Hepatically impaired subjects may have a history of or current hepatitis or be carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC).

Inclusion Criteria for Subjects with Normal Hepatic Function Only

• Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.
• Normal renal function as evidenced by CLcr that is within 20% of normal for the age, sex, and weight of the individual.

Exclusion Criteria:

• History of drug and/or alcohol abuse within 2 years prior to Screening.
• History of acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) antibodies.
• History of any significant drug allergy or known or suspected hypersensitivity.
• A positive urine alcohol test and/or urine drug screen for substance of abuse at Screening or upon admission to the study center.
• Subjects having taken an investigational drug within 30 days preceding study entry.
• Any history of significant bleeding or hemorrhagic tendencies. Subjects with a history of bleeding tendencies secondary to hepatic impairment will not be excluded.
• A history of difficulty in donating blood.
• The donation of blood or plasma within 30 days prior to dosing.
• Consumption of alcohol and/or food and beverages containing methylxanthines, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to dosing.
• Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to Screening through the end of the study.
• Subjects who have supine, sitting, or standing blood pressure, after resting for ≥ 3 minutes, higher than 140/90 mmHg or lower than 100/50 mmHg.
• Subjects who have a supine pulse rate, after resting for ≥ 3 minutes, outside the range of 40 to 90 bpm.
• Previous exposure to OPC-34712.
• Subjects who are pregnant or breastfeeding.
• Subjects with a QTcF interval ≥ 450 msec.
• Subjects with PT greater than 2 times control. Subjects with hepatic impairment with prolonged PT will be excluded based on the PI's discretion.
• Subjects with hepatic carcinoma or porto-hepatic shunts that have been surgically created or planted.
• Partial thromboplastin time > 70 seconds.

Exclusion Criteria for Hepatically Impaired Subjects Only:

• History of serious mental disorder including subjects who are pre-encephalopathic or encephalopathic as assessed by the Child-Pugh score and/or the PI's judgment.
• Major surgery of the digestive tract.

Exclusion Criteria for Subjects with Normal Hepatic Function Only:

• Clinically significant abnormality in past medical history.
• History of or current hepatitis, or carriers of HBsAg and/or anti-HC.
• Use of prescription, over-the-counter, herbal medication or vitamin supplements within 14 days prior to dosing and antibiotics within 30 days prior to dosing.
• History of serious mental disorders.
• Major surgery of the digestive tract (excluding appendectomy).