A Trial to Investigate the Efficacy and Safety of Orally Administered Tolvaptan (OPC-41061) in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

A Phase 2, Multicenter, Placebo-controlled, Double-blind, Randomized, Parallel-group Trial to Investigate the Efficacy and Safety of Orally Administered Tolvaptan (OPC-41061) in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

This is a study to investigate the efficacy and safety of OPC-41061 by 24-week oral administration of OPC-41061 at 15-mg or 30-mg or placebo in patients with chronic renal failure who are undergoing hemodialysis or hemodiafiltration and who have daily urine volume of at least 500 mL/day.

Inclusion Criteria:

• Chronic renal failure requiring hemodialysis or hemodiafiltration 3 times a week
• Daily urine volume of ≥ 500 mL/day
• Male or female patients age 20 to 80 years, inclusive
• Use of one of the specified contraceptive methods until 4 weeks after final IMP administration
• Capable of providing their own written informed consent prior to any trial-related procedures being performed

Exclusion Criteria:

• Patients with a complication of urinary impairment due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause
• Patients with NYHA class IV heart failure
• Patients with impaired hepatic function(chronic hepatitis, drug-induced liver injury)
• Patients with serious ischemic heart disease who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial
• Patients with serious arrhythmia who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial
• Patients with serious secondary hyperparathyroidism(intact parathyroid hormone > 500 pg/mL)
• Patients who are concomitantly undergoing peritoneal dialysis
• Patients with a history of cerebrovascular disease or coronary artery disease within 4 weeks prior to informed consent, a history of hypersensitivity to any ingredient of tolvaptan or benzazepine derivatives such as mozavaptan hydrochloride or a history of impaired hepatic function(chronic hepatitis, drug-induced liver injury)
• Patients with any of the following abnormal laboratory values: hemoglobin < 8.0 g/dL, total bilirubin > 3.0 mg/dL, ALT (GPT) or AST (GOT) > 2 times the upper limit of the reference range, serum sodium > upper limit of the reference range, serum sodium < 125 mEq/L, or serum potassium > 6.0 mEq/L
• Patients who are unable to sense thirst or who have difficulty with fluid intake
• Patients who have received OPC-41061 in history.
• Participation in any other clinical trial or post-marketing clinical study within 4 weeks prior to informed consent for the present trial
• Female patients who are pregnant, possibly pregnant, or nursing
• Patients otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial