A Trial of OPC-41061 in Patients With Hepatic Edema - Investigation of the Safety of Treatment at 7.5 mg Beyond 7 Days and of the Effect of Dose Escalation to 15 mg - Full Text View

Sponsor:	Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):	Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01048788

Purpose

OPC-41061 will be orally administered at 7.5 mg/day for 7 days to cirrhosis patients with ascites despite having received conventional diuretic therapy. Based on the change in body weight, on Day 7 it will be decided whether to continue administration at the same dose or to increase the dose, and then OPC-41061 will be orally administered for an additional 7 days at either 7.5 mg/day or, if diuretic effect for the initial 7-day administration is insufficient, at an increased dose of 15 mg/day. Plasma drug level, efficacy, and safety of OPC-41061 by 14-day repeated administration will be investigated.

Condition	Intervention	Phase
Cirrhosis	Drug: OPC-41061	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multicenter, Uncontrolled, Open-label Phase 3 Trial of OPC-41061 in Patients With Hepatic Edema - Investigation of the Safety of Treatment at 7.5 mg Beyond 7 Days and of the Effect of Dose Escalation to 15 mg

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Edema

Drug Information available for: Tolvaptan

U.S. FDA Resources

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

Primary Outcome Measures:

Adverse events, clinical laboratory tests, vital signs, and 12-lead ECG [ Time Frame: every week ] [ Designated as safety issue: Yes ]
Body weight, ascites (measured by ultrasonography), and clinical symptoms associated with ascites [ Time Frame: every week ] [ Designated as safety issue: No ]
Serum sodium concentration, plasma AVP concentration, daily urine volume, daily fluid intake, and fluid balance [ Time Frame: every week ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	December 2009
Study Completion Date:	August 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: OPC	Drug: OPC-41061 OPC-41061 tablets will be orally administered once daily after breakfast at 7.5 mg on Day 1 to 7 and at either 7.5 or 15 mg on Day 8 to 14.

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
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 mmHg
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01048788

Locations

Japan

Chubu Region, Japan

Chugoku Region, Japan

Kanto Region, Japan

Kinki Region, Japan

Kyushu Region, Japan

Tohoku Region, Japan

Sponsors and Collaborators

Otsuka Pharmaceutical Co., Ltd.

More Information

No publications provided

Responsible Party:	Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01048788 History of Changes
Other Study ID Numbers:	156-08-002, JapicCTI-100983
Study First Received:	January 7, 2010
Last Updated:	August 24, 2011
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 February 02, 2012