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

Ascites Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359462
• Other study ID #: 156-09-806-01
• Status: Completed
• Phase: Phase 1
• First received: March 5, 2010
• Last updated: May 23, 2011
• Start date: April 2009
• Est. completion date: January 2010

Study information

• Verified date: May 2011
• Source: Otsuka Beijing Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: January 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ? and?);

• 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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Hepatic Cirrhosis
• Liver Cirrhosis

Intervention

Drug:
• tolvaptan
Drug: tolvaptan tablet, 15mg, Qd, for 7 days.

Locations

Country	Name	City	State
China	Renji Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Beijing Research Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	pharmacological parameter:24-hr urine		From day-1 to day 8	No