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

• ClinicalTrials.gov Identifier: NCT01114828
• Recruitment Status: Completed
• First Posted: May 3, 2010
• Results First Posted: January 31, 2014
• Last Update Posted: March 4, 2014
• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Co., Ltd.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Cirrhosis	Drug: OPC-41061	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: February 2010
• Actual Primary Completion Date: October 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Body Weight [ Time Frame: Bseline, Day 7 or at the discontined of treatment ]
   Changes from baseline (day-1) for body weight at the end of treatment (LOCF) were calculated.

Secondary Outcome Measures :

1. Ascites Volume as Measured by CT [ Time Frame: Baseline, Day 7 or at the discontinued of treatment ]
   Change from baseline (day-1) for ascites volume as measured by CT at the end of treatment (LOCF) were calculated.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01114828
• Other Study ID Numbers: 156-09-004; JapicCTI-101112 ( Other Identifier: JAPIC )
• First Posted: May 3, 2010
• Results First Posted: January 31, 2014
• Last Update Posted: March 4, 2014
• Last Verified: January 2014

Keywords provided by Otsuka Pharmaceutical Co., Ltd.:

Cirrhosis; ascites; Tolvaptan; OPC-41061

Additional relevant MeSH terms:

Fibrosis; Pathologic Processes; Tolvaptan; Antidiuretic Hormone Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Physiological Effects of Drugs