A Dose-defining Study of OPC-41061 in Treatment of Hepatic Edema

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT00479336
First received: May 25, 2007
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

To investigate the dose response for changes from baseline in body weight as a primary endpoint and to investigate improvement in ascites, abdominal circumference, lower-limb edema, and pleural effusion as secondary endpoints in seven-day repeated oral administration of OPC-41061 at 7.5, 15, and 30 mg/day or placebo in cirrhosis patients with ascites despite taking conventional diuretics.


Condition Intervention Phase
Cirrhosis
Drug: OPC-41061 7.5mg
Drug: OPC-41061 placebo
Drug: OPC-41061 15mg
Drug: OPC-41601 30mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Dose-defining Study of OPC-41061 in Treatment of Hepatic Edema

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Body Weight (Amount of Change) [ Time Frame: Baseline, Day 7 or at the discontied of treatment ] [ Designated as safety issue: No ]
    Changes in body wight from baseline at the final timepoint (LOCF). A linear regression model using changes in body weight from baseline at the final timepoint as the criterion variable and dose as the explanatory variable was fitted to the dataset.


Secondary Outcome Measures:
  • Abdominal Circumference [ Time Frame: Baseline, Day 7 or at the discontied of treatment ] [ Designated as safety issue: No ]
    Change in abdominal circumference from baseline (LOCF)


Enrollment: 104
Study Start Date: June 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Drug: OPC-41061 placebo
placebo, 1 tablet a day
Experimental: 2 Drug: OPC-41061 7.5mg
7.5mg, 1 tablet a day
Experimental: 3 Drug: OPC-41061 15mg
15mg, 1 tablet a day
Experimental: 4 Drug: OPC-41601 30mg
30mg, 1 tablet a day

  Eligibility

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

Inclusion Criteria:

  1. Subjects with ascites despite taking either of the following combinations of loop diuretics and an anti-aldosterone agent (spironolactone) for at least 7 days prior to start of the study drug administration.

    Combination 1: Loop diuretics at indicated below in combination with an anti-aldosterone agent at a daily dose of 25 mg or more

    • Furosemide: 40 mg/day or more
    • Other loop diuretic: a daily dosage equivalent to 40 mg or more of furosemide Bumetanide: 1 mg/day or more, Piretanide: 6 mg/day or more, Azosemide: 60 mg/day or more, Torasemide: 8 mg/day or more Combination 2: Anti-aldosterone agent at a daily dose of 50 mg or more in combination with furosemide at a daily dose of 20 mg or more (or one of the other loop diuretics specified in Combination 1 at a daily dosage equivalent to 20 mg or more of furosemide)
  2. Patients who have been hospitalized or are able to stay at the study site from the start of the run-in observation period until completion of postdosing observation 2.
  3. Subjects capable of giving informed consent to participate in the study of their own free will.

Exclusion Criteria:

  1. Subjects with any of the following complications or symptoms: (1) Hepatic encephalopathy (Hepatic coma grade: II or more), (2) Poorly-controlled hepatocellular carcinoma (i.e., hepatocellular carcinoma with vessel infiltration confirmed by imaging in the main trunk or main branch of the portal vein, inferior vena cava, or the main trunk of the hepatic vein), (3)Endoscopic findings within 30 days prior to screening examination requiring new therapy for esophageal and gastric varicose vein during the study period, (4)Repeated haemorrhoidal bleeding due to rectal varicose vein within 30 days prior to screening examination, (5)Diabetes mellitus with poorly controlled blood glucose, (6)Heart failure (NYHA class III or IV), (7)Anuria, (8)Impairment of urination due to urinary tract stricture, urinary calculus, tumor in the urinary tract, or other cause
  2. Subjects with a history of any of the following diseases: (1) Cerebrovascular disorder within 30 days prior to the screening examination, (2)Episode of gout within 90 days prior to the screening examination, (3)Hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride.
  3. Subjects who are obese (body mass index [BMI, body weight (kg)/height (m)2] exceeding 35)
  4. Patients with supine systolic blood pressure exceeding 90 mmHg
  5. Subjects with any of following abnormal laboratory values: hemoglobin exceeding 8.0 g/dL, total bilirubin exceeding 3.0 mg/dL, serum creatinine exceeding 3.0 mg/dL, serum sodium exceeding 147 mEq/L, serum potassium exceeding 5.5 mEq/L, or uric acid exceeding 8.0 mg/dL
  6. Patients who are unable to take oral medication
  7. Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant
  8. Subjects who received blood products, including albumins, within 7 days prior to the screening examination
  9. Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination
  10. Subjects who previously participated in this or any other study of OPC-41061 and received OPC-41061
  11. Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the study
  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: NCT00479336

Locations
Japan
Chubu region, Japan
Chugoku region, Japan
Hokkaido region, Japan
Kanto region, Japan
Kinki region, Japan
Kyusyu region, Japan
Tohoku region, Japan
Sponsors and Collaborators
Otsuka Pharmaceutical Co., Ltd.
Investigators
Study Director: Katsuhisa Saito Division of New Product Evalution and Development
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT00479336     History of Changes
Other Study ID Numbers: 156-06-005
Study First Received: May 25, 2007
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.:
OPC-41061
Tolvaptan
ascites
Cirrhosis

ClinicalTrials.gov processed this record on September 22, 2014