Multiple-dose Pharmacokinetics Study of Tolvaptan Tablets in Chinese Patients With Hepatocirrhosis

This study is to evaluate the multiple-dose pharmacokinetics, pharmacological actions and safety of Tolvaptan tablets administered orally (15 mg daily) for consecutively 7 days in Chinese adult patients with confirmed Child-Pugh Class B（score 7-9） hepatocirrhosis (accompanied by ascites).

Trial Design:

• Open, single-center, multi-dose pharmacokinetics study
• Study population:

Chinese adult patients with confirmed Child-Pugh Class B (score 7-9) hepatocirrhosis (accompanied by ascites)

• Dosage and mode of administration of investigational product:

Oral administration of 1 tablet (15mg) once daily, for consecutive 7 days starting from day 1 of treatment.

• Study duration:

Screening: 14 days in maximum; Treatment(s): 7 days; Observation: 1 day

Inclusion criteria

• Hepatic Cirrhosis with ascites or lower extremities edema
• Hospitalized patients
• 18 years old~75 years old
• Inform Consent Form Signed

Exclusion criteria

• Patients with any of the following diseases, complications or symptoms:

• Hepatic encephalopathy (coma degree classification note 1 Grade 2 or above);
• Malignant ascites;
• Spontaneous bacterial peritonitis;
• Likely to have gastrointestinal bleeding during the study period;
• Heart failure (NYHA Note 2 Class Ⅲ andⅣ);
• Anuria (daily urine output below 100mL);
• Dysuria induced by urinary tract stenosis, calculus, or tumor.
• Patients with any of the following history:

• With gastrointestinal bleeding within 10 days prior to screening;
• With cerebrovascular accident within 1 month prior to screening;
• With gout attack within 1 month prior to screening;
• With allergy or atopy to benzodiazepine drugs (benazepril hydrochloride, etc.).
• Patients whose systolic blood pressure is below 90mmHg during screening;
• Patients with abnormal values in the following lab examination indicators:

Serum creatinine higher than 2.5 times the upper limit of normal range, serum Na+>145mmol/L(or higher than the upper limit of normal range), serum K+> 5.5 mmol/L, uric acid>476µmol/L, child-Pugh score>10

• Patients ineligible for oral medication
• Patients in pregnancy or lactation; female of childbearing potential not taking contraceptive measures;
• Patients having taken blood products including albumin products within 4 days prior to application of investigational product;
• Patients having participated in clinical trials of other drugs within 1 month prior to screening;
• Patients used to participate in clinical trials of Tolvaptan and take the said drug;
• Patients determined by the investigator as illegible for the study.