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

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

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

Study Overview

• Status: Completed
• Conditions: Ascites; Hepatic Cirrhosis
• Intervention / Treatment: Drug: tolvaptan

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

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tolvaptan 15mg tablet	Drug: tolvaptan; Drug: tolvaptan tablet, 15mg, Qd, for 7 days.; Other Names: SAMSCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): November 1, 2009
• Study Completion (ACTUAL): January 1, 2010

Study Registration Dates

• First Submitted: March 5, 2010
• First Submitted That Met QC Criteria: May 23, 2011
• First Posted (ESTIMATE): May 24, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 24, 2011
• Last Update Submitted That Met QC Criteria: May 23, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: hepatic cirrhosis patients with ascites
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-09-806-01