A Multicenter, Open-label, Dose-finding Trial of OPC-41061 to Investigate Efficacy, Pharmacokinetics, Pharmacodynamics, and Safety in Patients With Carcinomatous Edema (Phase 2)

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Open-label, Dose-finding Trial of OPC-41061 to Investigate Efficacy, Pharmacokinetics, Pharmacodynamics, and Safety in Patients With Carcinomatous Edema (Phase 2)

Conditions
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Carcinomatous Edema

Intervention / Treatment
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* Drug: OPC-41061


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPC-41061<br> | Drug: OPC-41061<br>* orally administered at 3.75, 7.5, 15, or 30 mg once daily after breakfast for up to 11 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight From Baseline at Final IMP Administration | Body weight was measured in 100-g units before breakfast and after subjects had urinated at least once, taking care to minimize fluctuations due to defecation or clothing. | Baseline, at the final IMP administration (shortest:7days longest:12days) | 
| Change in Ascites Volume From Baseline Measured by Computer Tomography (CT) at Final IMP Administration |  | Baseline, at the final IMP administration (shortest:7days longest:12days) |