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

NCT00479336 | Completed Phase 2 Results

• 1 other identifier: 156-06-005
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Cirrhosis

Keywords

OPC-41061; Tolvaptan; ascites; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Body Weight (Amount of Change)

  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.

  Baseline, Day 7 or at the discontied of treatment

Secondary Outcomes (1)

• Abdominal Circumference

  Baseline, Day 7 or at the discontied of treatment

Study Arms (4)

1

PLACEBO COMPARATOR

Drug: OPC-41061 placebo

2

EXPERIMENTAL

Drug: OPC-41061 7.5mg

3

EXPERIMENTAL

Drug: OPC-41061 15mg

4

EXPERIMENTAL

Drug: OPC-41601 30mg

Interventions

OPC-41061 7.5mg DRUG

7.5mg, 1 tablet a day

2

OPC-41061 placebo DRUG

placebo, 1 tablet a day

1

OPC-41061 15mg DRUG

15mg, 1 tablet a day

3

OPC-41601 30mg DRUG

30mg, 1 tablet a day

4

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.
• Subjects capable of giving informed consent to participate in the study of their own free will.

You may not qualify if:

• 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
• 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.
• Subjects who are obese (body mass index \[BMI, body weight (kg)/height (m)2\] exceeding 35)
• Patients with supine systolic blood pressure exceeding 90 mmHg
• 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
• Patients who are unable to take oral medication
• Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant
• Subjects who received blood products, including albumins, within 7 days prior to the screening examination
• Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination
• Subjects who previously participated in this or any other study of OPC-41061 and received OPC-41061

Sponsors & Collaborators

• Otsuka Pharmaceutical Co., Ltd.: lead

Study Sites (7)

Unknown Facility

Chubu Region, Japan

Location

Unknown Facility

Chugoku Region, Japan

Location

Unknown Facility

Hokkaido Region, Japan

Location

Unknown Facility

Kanto Region, Japan

Location

Unknown Facility

Kinki Region, Japan

Location

Unknown Facility

Kyusyu Region, Japan

Location

Unknown Facility

Tohoku Region, Japan

Location

MeSH Terms

Conditions

Fibrosis; Ascites

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director of Clinical Research and Development
• Organization: Otsuka Pharmaceutical Co., Ltd.

+81-3-6361-7366

Study Officials

• Katsuhisa Saito

  Division of New Product Evalution and Development

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2007
• First Posted: May 28, 2007
• Study Start: June 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: March 14, 2014
• Results First Posted: March 14, 2014

Record last verified: 2014-01

Locations

JP (7)