Carcinomatous Edema
Conditions
Brief 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.
Interventions
DRUGOPC-41061
orally administered at 3.75, 7.5, 15, or 30 mg once daily after breakfast for up to 11 days.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight From Baseline at Final IMP Administration | Baseline, at the final IMP administration (shortest:7days longest:12days) | 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. |
| 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) | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-41061 3.75 mg Orally administered at 3.75 mg once daily in maintenance period. | 13 |
| OPC-41061 7.5 mg Orally administered at 7.5 mg once daily in maintenance period. | 7 |
| OPC-41061 15 mg Orally administered at 15 mg once daily in maintenance period. | 9 |
| OPC-41061 30 mg Orally administered at 30 mg once daily in maintenance period. | 11 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Dose-escalation Period | Adverse Event | 0 | 1 | 0 | 0 |
| Dose-escalation Period | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Maintenance Period | Adverse Event | 1 | 1 | 1 | 1 |
| Maintenance Period | Physician Decision | 0 | 1 | 0 | 0 |
| Maintenance Period | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | OPC-41061 3.75 mg | OPC-41061 7.5 mg | OPC-41061 15 mg | OPC-41061 30 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 9.9 | 66.1 years STANDARD_DEVIATION 8.5 | 62.2 years STANDARD_DEVIATION 7.6 | 69.5 years STANDARD_DEVIATION 7.9 | 65.3 years STANDARD_DEVIATION 8.8 |
| Race/Ethnicity, Customized Japanese | 13 Participants | 7 Participants | 9 Participants | 11 Participants | 40 Participants |
| Region of Enrollment Japan | 13 Participants | 7 Participants | 9 Participants | 11 Participants | 40 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 7 Participants | 7 Participants | 24 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 2 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 8 | 0 / 9 | 0 / 11 |
| other Total, other adverse events | 8 / 15 | 6 / 8 | 8 / 9 | 10 / 11 |
| serious Total, serious adverse events | 1 / 15 | 0 / 8 | 0 / 9 | 0 / 11 |
Outcome results
Primary
Change in Ascites Volume From Baseline Measured by Computer Tomography (CT) at Final IMP Administration
Time frame: Baseline, at the final IMP administration (shortest:7days longest:12days)
Population: Full analysis set: all subjects who had been administered the IMP at least once and from whom data for efficacy endpoints were obtained after the start of IMP administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 3.75 mg | Change in Ascites Volume From Baseline Measured by Computer Tomography (CT) at Final IMP Administration | -77.20 mL | Standard Deviation 982.19 |
| OPC-41061 7.5 mg | Change in Ascites Volume From Baseline Measured by Computer Tomography (CT) at Final IMP Administration | 513.97 mL | Standard Deviation 653.3 |
| OPC-41061 15 mg | Change in Ascites Volume From Baseline Measured by Computer Tomography (CT) at Final IMP Administration | 153.72 mL | Standard Deviation 993.63 |
| OPC-41061 30 mg | Change in Ascites Volume From Baseline Measured by Computer Tomography (CT) at Final IMP Administration | 539.93 mL | Standard Deviation 659.36 |
Primary
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.
Time frame: Baseline, at the final IMP administration (shortest:7days longest:12days)
Population: Full analysis set: all subjects who had been administered the IMP at least once and from whom data for efficacy endpoints were obtained after the start of IMP administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 3.75 mg | Change in Body Weight From Baseline at Final IMP Administration | -0.69 Kg | Standard Deviation 2.51 |
| OPC-41061 7.5 mg | Change in Body Weight From Baseline at Final IMP Administration | -0.34 Kg | Standard Deviation 1.99 |
| OPC-41061 15 mg | Change in Body Weight From Baseline at Final IMP Administration | -1.13 Kg | Standard Deviation 1.62 |
| OPC-41061 30 mg | Change in Body Weight From Baseline at Final IMP Administration | 0.70 Kg | Standard Deviation 1.56 |