Open-label Dose-finding Trial of OPC-41061 in Patients With Chronic Renal Failure Undergoing Peritoneal Dialysis

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 Peritoneal Dialysis

To investigate the efficacy, pharmacokinetics, pharmacodynamics, and safety of OPC-41061 in patients with chronic renal failure who are undergoing peritoneal dialysis, using daily urine volume, body weight, and edematous conditions as parameters and conducting dose escalation every 2 days until reaching the dose that achieves urine volume increase and then performing 5-day repeated administration at the fixed dose, the final dose used in the dose escalation period.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chubu Region, Japan
  • Hokkaido Region, Japan
  • Kanto Region, Japan
  • Kyushu Region, Japan
  • Shikoku Region, Japan
  • Tohoku Region, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with chronic renal failure
• Patients who are undergoing peritoneal dialysis (continuous ambulatory peritoneal dialysis [CAPD])

• Patients who, after undergoing peritoneal dialysis, received any of the following medical treatments for fluid overload [OR: hypervolemia] that had insufficient effect:

  • Addition or increase of diuretics
  • Increase in concentration or volume of peritoneal dialysis fluid
  • Increase in the number of changes of peritoneal dialysis fluid
• 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
• Subjects who are inpatients or who can be admitted to the trial site for the duration of the trial period

Exclusion Criteria:

• Subjects with any of the following diseases, complications, or symptoms:

  • Suspected hypovolemia
  • Daily urine volume less than 200 mL
  • Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause
  • Cardiac function of NYHA class 4

• 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 9.0 g/dL, total bilirubin higher than 3.0 g/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 125 mEq/L, or serum potassium higher than 5.5 mEq/L

• Subjects with any of the following conditions, concomitant diseases, or symptoms:

  • defect in diaphragm
  • hemorrhagic diathesis due to uremia
  • suspected lactic acid metabolic disorder
  • suspected peritonitis, peritoneal damage, peritoneal adhesion, or disorders in intraabdominal organs
• Subjects who have undergone peritoneal dialysis for 8 years or longer
• Subjects who are scheduled to undergo hemodialysis or concomitant use of hemodialysis, or renal transplantation
• Subjects who have participated in any other clinical trial or post-marketing clinical studies within 30 days prior to informed consent
• Subjects who have previously received OPC-41061
• Subjects who are unable to sense thirst or who have difficulty with fluid or food intake
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPC-41061	Drug: OPC-41061

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Daily Urine Volume From Baseline	Change in daily urine volume from baseline during the repeated-administration period (For five days).	Urine Volume on day13 minus Urine Volume at baseline(day9) on the repeated-administration period.
Percent Change in Daily Urine Volume From Baseline	Percent change in daily urine volume from baseline during the repeated-administration period (For five days).	100%*<Urine Volume on day13 minus Urine Volume at baseline(day9) on the repeated-administration period/Urine Volume at baseline(day9) on the repeated-administration period>

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight From Baseline	Change in body weight from baseline during the repeated-administration period(For five days).	Body weight on day13 minus Body weight at baseline(day9) on the repeated-administration period
Percent Change in Body Weight	Percent change in body weight from baseline during the repeated-administration period(For five days).	100%*<Body weight on day13 minus Body weight at baseline (day9)/Body weight at baseline(day9)>

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: July 4, 2013
• First Submitted That Met QC Criteria: July 4, 2013
• First Posted (Estimate): July 10, 2013

Study Record Updates

• Last Update Posted (Estimate): January 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: dialysis; Tolvaptan
• 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: 156-12-002; JapicCTI-132181 (Other Identifier: Japan Pharmaceutical Information Center)