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

Otsuka

Status and phase

Completed

Phase 2

Conditions

Carcinomatous Edema

Treatments

Drug: OPC-41061

Study type

Interventional

Funder types

Industry

Identifiers

NCT01684202

JapicCTI-121957 (Other Identifier)

156-12-001

Details and patient eligibility

About

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.

Enrollment

43 patients

Sex

All

Ages

20 to 80 years old

Volunteers

No Healthy Volunteers

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