A Study to Investigate Pharmacodynamics and Pharmacokinetics of OPC-41061 in Patients With Hepatic Edema

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01114828
First received: April 29, 2010
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

OPC-41061 at 3.75 mg/day or 7.5 mg/day will be orally administered once daily for 7 days to cirrhosis patients with ascites despite having received treatment with conventional diuretics and pharmacodynamics, pharmacokinetics, efficacy, and safety will be investigated.


Condition Intervention Phase
Cirrhosis
Drug: OPC-41061
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Double-blind, Parallel-arm Study to Investigate Pharmacodynamics and Pharmacokinetics of OPC-41061 in Patients With Hepatic Edema

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Co., Ltd.:

Primary Outcome Measures:
  • Body Weight [ Time Frame: Bseline, Day 7 or at the discontined of treatment ] [ Designated as safety issue: No ]
    Changes from baseline (day-1) for body weight at the end of treatment (LOCF) were calculated.


Secondary Outcome Measures:
  • Ascites Volume as Measured by CT [ Time Frame: Baseline, Day 7 or at the discontinued of treatment ] [ Designated as safety issue: No ]
    Change from baseline (day-1) for ascites volume as measured by CT at the end of treatment (LOCF) were calculated.


Enrollment: 40
Study Start Date: February 2010
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3.75 mg
Once-daily oral administration of OPC-41061
Drug: OPC-41061
Once-daily oral administration of OPC-41061 at 3.75 mg after breakfast for 7 days
Experimental: 7.5 mg
Once-daily oral administration of OPC-41061
Drug: OPC-41061
Once-daily oral administration of OPC-41061 at 7.5 mg after breakfast for 7 days

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients judged as having cirrhosis based on previous imaging diagnosis (Definition of cirrhosis includes patients with collateral circulation due to chronic hepatic impairment)
  • Patients with ascites in whom the dose of existing diuretics cannot be increased due to risk of adverse drug reactions such as electrolyte abnormalities, or in whom sufficient therapeutic effect cannot be obtained with existing diuretics
  • Patients who have been receiving oral combination therapy with a loop diuretic and an anti-aldosterone agent from at least 7 days prior to receipt of informed consent, with a dose combination of either loop diuretic equivalent to furosemide 40 mg/day or higher plus spironolactone 25 mg/day or higher, or loop diuretic equivalent to furosemide 20 mg/day or higher plus spironolactone 50 mg/day or higher
  • Patients who are hospitalized or who can be hospitalized for the trial - Age 20 to 80 years inclusive
  • Patients capable of giving informed consent
  • Patients who, together with their partner, agree to use an appropriate method of contraception until 4 weeks after the final trial drug administration

Exclusion Criteria:

  • Patients with any of the following complications or symptoms:

    • Hepatic encephalopathy (hepatic coma of grade 2 or higher)
    • Hepatocellular carcinoma with imaging-diagnosed vascular infiltration into trunk or primary branch of portal vein, inferior vena cava, or trunk of hepatic vein
    • Endoscopic findings from screening examination or from within 30 days prior to screening examination indicating the need for new therapy for esophageal or gastric varices during the trial period
    • Repeated hemorrhoidal bleeding due to rectal varicose veins within 30 days prior to informed consent
    • Heart failure (New York Heart Association Class III or IV)
    • Anuria
    • Impaired urination due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause
  • Patients with a history of any of the following disorders:

    • Cerebrovascular disorder within 30 days prior to informed consent
    • Hypersensitivity or idiosyncratic reaction to benzazepine derivatives (such as mozavaptan hydrochloride or benazepril hydrochloride) "
  • Morbidly obese patients with a body mass index (BMI: body weight (kg)/height (m)2) exceeding 35
  • Patients with sitting systolic blood pressure lower than 90 mm Hg
  • Patients with any of following abnormal clinical laboratory values at time of the screening examination: Hemoglobin lower than 8.0 g/dL, total bilirubin higher than 4.0 mg/dL, serum creatinine higher than 2.0 mg/dL, serum sodium higher than 147 mEq/L, or serum potassium higher than 5.5 mEq/L
  • Patients who are unable to take oral medication
  • Female patients who are pregnant, possibly pregnant, or breast-feeding, or who are planning to become pregnant
  • Patients who have used albumin preparations (therapeutic agents for hypoalbuminemia) or blood products containing albumin from within 7 days prior to informed consent
  • Patients who received any investigational drug other than OPC-41061 within 30 days prior to informed consent
  • Patients who have previously received OPC-41061
  • Any patient who, in the opinion of the principle investigator or subinvestigator, is inappropriate for participation in the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01114828

Locations
Japan
Tokyo, et al., Japan
Sponsors and Collaborators
Otsuka Pharmaceutical Co., Ltd.
Investigators
Study Director: Katsuhisa Saito Department of Clinical Research and Development, Otsuka Pharmaceutical Co., Ltd.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT01114828     History of Changes
Other Study ID Numbers: 156-09-004, JapicCTI-101112
Study First Received: April 29, 2010
Results First Received: December 15, 2013
Last Updated: January 30, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Otsuka Pharmaceutical Co., Ltd.:
Cirrhosis
ascites
Tolvaptan
OPC-41061

Additional relevant MeSH terms:
Liver Cirrhosis
Fibrosis
Liver Diseases
Digestive System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014