Open-label Dose-finding Trial of OPC-41061 in Patients With Chronic Renal Failure Undergoing Peritoneal Dialysis
Condition: Chronic Renal Failure
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic; Renal Insufficiency, Chronic
Intervention: OPC-41061
Intervention MeSH terms: Tolvaptan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Healthy volunteers: No
Keywords: Tolvaptan; dialysis

Summary:

      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.
    

Eligibility criteria:

        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