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

Study Overview
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Brief Summary
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For hepatic cirrhosis subjects with ascites or lower extremities, to study Pharmacokinetics, pharmacology, and safety of the drug under fasting condition.

Detailed Description
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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

Official Title
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A Clinical Study of Multiple-dose Pharmacokinetics of Tolvaptan Tablets Administered Orally (15mg Daily) for Consecutively 7 Days in Chinese Patients With Hepatocirrhosis

Conditions
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Ascites, Hepatic Cirrhosis

Intervention / Treatment
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* Drug: tolvaptan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolvaptan 15mg tablet<br> | Drug: tolvaptan<br>* Drug: tolvaptan tablet, 15mg, Qd, for 7 days.<br>* Other names: SAMSCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of tolvaptan and its metabolites DM-4103 and DM-4107 |  | blood sample will be collected at predose, 2,4,6,8,12,24 hour of first drug administration and predose of sixth drug administration and predose,2,4,6,8,12,24 hour of seventh drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacological parameter:Serum concentration of sodium and potassium |  | Blood sample will be collected at predose on day1;12,24hour of first dosing;before breakfast on day3 to day6;predose and 12,24hour of seventh dosing | 
| pharmacological parameter:24-hr urine |  | From day-1 to day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatic cirrhosis patients with ascites