A Multicenter, Open-label, Dose-finding Trial of OPC-41061 to Investigate Efficacy, Pharmacokinetics, Pharmacodynamics, and Safety in Patients With Carcinomatous Edema (Phase 2)
Condition: Carcinomatous Edema
MeSH terms: Edema
Intervention: OPC-41061
Intervention description: orally administered at 3.75, 7.5, 15, or 30 mg once daily after breakfast for up to 11 days.
Intervention MeSH terms: Tolvaptan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 20 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      OPC-41061 will be administered to patients with volume overload associated with cancer, first
      by dose-escalation and subsequently for 6 consecutive days at the fixed dose at which urine
      volume is increased to investigate efficacy, pharmacokinetics, pharmacodynamic effects, and
      safety and to determine the effective initial and maintenance doses of OPC-41061.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects judged as having cancer by biopsy or cytology

          -  Subjects with carcinomatous ascites

          -  Male or female subjects between the ages of 20 and 80, inclusive (at time of informed
             consent)

          -  Subjects with survival expectancy of at least 3 months and an Eastern Cooperative
             Oncology Group (ECOG) Performance Status score (PS score) of 0 to 2

          -  Subjects who are inpatients or who can be admitted to the trial site for the duration
             of the trial

          -  Subjects who, together with their partner, are able to practice one of the specified
             contraceptive methods until 4 weeks after final trial drug administration

          -  Subjects capable of giving informed consent to participate in the trial of their own
             free will prior to start of the trial.

        Exclusion Criteria:

          -  Subjects with any of the following complications or symptoms:

               -  Deep vein thrombosis

               -  Intestinal obstruction or intestinal edema with symptoms similar to intestinal
                  obstruction

               -  Hepatic cirrhosis

               -  Anuria

               -  Urination impaired due to urinary tract stricture, urinary calculus, tumor in
                  urinary tract, or other cause

               -  Continuing symptoms of diarrhea or vomiting

               -  Infection requiring systemic treatment

          -  Subjects with any of the following medical histories:

               -  History of cerebrovascular disorder or coronary disease within 4 weeks prior to
                  start of the pre-observation period

               -  History of hypersensitivity or idiosyncratic reaction to benzazepine derivatives
                  such as mozavaptan hydrochloride or benazepril hydrochloride

               -  History of gastrectomy or enterectomy to an extent affecting absorption of oral
                  medication

          -  Subjects with any of the following abnormal laboratory values:

        Platelet count of < 75,000/mm3, hemoglobin of < 8.0 g/dL, neutrophil count of < 1,000/mm3,
        total bilirubin of > 4.0 g/dL, serum creatinine of > 3.0 mg/dL, serum sodium of > 147
        mEq/L, or serum potassium of > 5.5 mEq/L

          -  Subjects who have used albumin products (agents for treating hypoalbuminemia) or blood
             products containing albumins within 1 week prior to start of the pre-observation
             period, or after start of the pre-observation period

          -  Subjects who have received any investigational drug within 4 weeks prior to start of
             the pre-observation period

          -  Subjects who have previously received OPC-41061

          -  Subjects who have received surgical treatment or radiation therapy for cancer within 4
             weeks prior to start of the pre-observation period

          -  Subjects for whom the investigator or subinvestigator judges that it would be
             difficult to evaluate the efficacy and safety of OPC-41061 due to the effects of
             ongoing chemotherapy or other therapies for cancer (eg, improvement of carcinomatous
             ascites or development of edema due to adverse events related to therapeutic
             interventions other than OPC-41061)

          -  Subjects who are unable to sense thirst or who have difficulty with fluid or food
             intake

          -  Subjects who are unable to take oral medication

          -  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