A Phase 2, Multi-center, Open-label, Dose-finding Trial to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of OPC-41061 in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

To investigate the safety, pharmacokinetics, pharmacodynamics, and efficacy of OPC-41061 in patients with chronic renal failure undergoing hemodialysis or hemodiafiltration using variables, such as daily urine volume and increase in interval body weights between hemodialysis or hemodiafiltration, in 4-day intermittant administration (excluding the days of hemodialysis or hemodiafiltration) at the dose fixed during the dose-escalation period

Study Overview

• Status: Completed
• Conditions: Chronic Renal Failure
• Intervention / Treatment: Drug: OPC-41061

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chube Region, Japan
  • Kanto Region, Japan
  • Kinki Region, Japan
  • Kyushu Region, Japan
  • Tohoku Region, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with chronic renal failure who are undergoing hemodialysis or hemodiafiltration three times a week
• Subjects between the ages of 20 and 80, inclusive (at time of informed consent)
• Subjects who are inpatients or who can be admitted to the trial site for the duration of the trial period
• Subjects who, together with their partner, are able to practice one of the specified contraceptive methods until 4 weeks after the final trial drug administration
• Patients who are capable of providing written informed consent themselves before any trial-related procedures are performed

Exclusion Criteria:

• Subjects with a complication of urinary impairment due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause
• Subject with daily urine volume less than 500 mL
• Subject with Cardiac function of NYHA class 4
• Subjects with serious ischemic heart disease, who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial
• Subjects with serious arrhythmia, who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial
• Subjects who are concomitantly undergoing peritoneal dialysis
• Subjects with ascites due to cirrhosis or cancer, requring medical treatments

• Subjects with any of the following medical histories:

  • History of cerebrovascular disorder or coronary artery disease within 4 weeks prior to informed consent
  • History of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride

• Subjects with any of the following abnormal laboratory values:

  • Hemoglobin lower than 8.0 g/dL, total bilirubin higher than 3.0 mg/dL, ALT (GPT) or AST (GOT) 2 times the upper limit of the reference range of the trial site, serum sodium higher than the upper limit of the reference range of the trial site, serum sodium lower than 125mEq/L
• Subjects with serum potassium higher than 6.0mEq/L and abnormal findings inappropriate for inclusion in the trial are observed by 12-lead ECG
• Subjects who are unable to sense thirst or who have difficulty with fluid or food intake
• Subjects who have participated in any other clinical trial or post-marketing clinical studies within 4 weeks prior to informed consent
• Female subjects who are pregnant, possibly pregnant, or nursing, or who plan to become pregnant during the trial period
• Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: OPC-41061	Drug: OPC-41061; The maximum number of days of administration will be 8 days (8 doses) in total 4 days each in the dose-escalation period and intermittant administration period. The investigational medicinal product (IMP) will be administered once daily after breakfast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Urine Volume	The daily urine volume at each timepoint and its change and the percent change from baseline will be summarized with descriptive statistics (number, mean, standard deviation [SD], minimum, median, maximum [same for following parameters]).	Baseline and Day 14 (Intermittent Administration Period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Fluid Removal Per Week by Dialysis	The total volume of fluid removed per week by dialysis at each timepoint and its change from baseline will be summarized with descriptive statistics.	Baseline (pretreatment observation period) and Intermittent Administration Period (Day 10 to Day 15)

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Kyoji Imaoka, Mr, Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: June 9, 2013
• First Submitted That Met QC Criteria: June 9, 2013
• First Posted (ESTIMATE): June 12, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-12-007; JapicCTI-132147 (OTHER: JAPIC)