Clinical trial NCT01359462: Multiple-dose Pharmacokinetics Study of Tolvaptan Tablets in Chinese Patients With Hepatocirrhosis
Official title: A Clinical Study of Multiple-dose Pharmacokinetics of Tolvaptan Tablets Administered Orally (15mg Daily) for Consecutively 7 Days in Chinese Patients With Hepatocirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Cirrhosis
Ascites
Keywords: hepatic cirrhosis patients with ascites
Lead sponsor: Otsuka Beijing Research Institute
Sponsor class: INDUSTRY
First posted: 2011-05-24
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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:

1. Open, single-center, multi-dose pharmacokinetics study
2. Study population:

   Chinese adult patients with confirmed Child-Pugh Class B (score 7-9) hepatocirrhosis (accompanied by ascites)
3. 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.
4. Study duration:

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

Eligibility criteria: Inclusion Criteria:

1. Hepatic Cirrhosis with ascites or lower extremities edema
2. Hospitalized patients
3. 18 years old\~75 years old
4. Inform Consent Form Signed

Exclusion Criteria:

1. 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.
2. 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.).
3. Patients whose systolic blood pressure is below 90mmHg during screening;
4. 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
5. Patients ineligible for oral medication
6. Patients in pregnancy or lactation; female of childbearing potential not taking contraceptive measures;
7. Patients having taken blood products including albumin products within 4 days prior to application of investigational product;
8. Patients having participated in clinical trials of other drugs within 1 month prior to screening;
9. Patients used to participate in clinical trials of Tolvaptan and take the said drug;
10. Patients determined by the investigator as illegible for the study.

Primary outcomes:
measure: Serum concentration of tolvaptan and its metabolites DM-4103 and DM-4107
timeFrame: 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 outcomes:
measure: pharmacological parameter:Serum concentration of sodium and potassium
timeFrame: 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
measure: pharmacological parameter:24-hr urine
timeFrame: From day-1 to day 8
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Minde Zeng
role: PRINCIPAL_INVESTIGATOR
References: