Cardiac Edema
Conditions
Keywords
Vasopressin antagonist , Cardiac Edema ,Diuretics
Brief summary
To investigate the plasma drug level, efficacy, and safety of 7-day repeated oral administration of OPC-41061 at 15 mg/day (treatment period 1) and subsequent 7-day repeated administration of OPC-41061 at 15 mg/day or 30 mg/day if diuretic effect is insufficient (treatment period 2) in congestive heart failure (CHF) patients with extracellular volume expansion despite conventional diuretic therapy.
Interventions
DRUGOPC-41061 （Tolvaptan)
15-30mg/day,daily for 14days
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 85 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects with cardiac edema receiving diuretic treatment since 7 days prior to the commencement of study drug administration. 2. Subjects receiving one of the following diuretic treatments since 3 days prior to the commencement of study drug administration without changing the dose or dosing regimen (including subjects scheduled to start treatment during the run-in observation period). * 1\. A loop diuretic at a daily dosage equivalent to 40 mg or more of furosemide * 2\. Concomitant administration of a loop diuretic and a thiazide diuretic (at any doses) * 3\. Concomitant administration of a loop diuretic and an anti-aldosterone drug (at any doses) 3. CHF patients with lower limb edema, jugular venous distention, or pulmonary congestion due to extracellular volume expansion. 4. Male or female subjects between the ages of 20 and 85, inclusive (at time of informed consent) 5. Subjects able to stay at the study site from the day before the start of the run-in observation period until completion of post-treatment observation 2 (7 to 10 days after final study drug administration) 6. Subjects capable of giving informed consent to participate in the study of their own free will
Exclusion criteria
1. Heart failure patients with markedly fluctuating symptoms 2. Patients with an assisted circulation device 3. Patients with any of the following complications or symptoms: * 1\. Suspected decrease in circulatory blood flow ， * 2\. Hypertrophic cardiomyopathy (other than dilated phase)， * 3\. Cardiac valve disease with significant heart valve stenosis， * 4\. Hepatic coma 4. Patients who develop acute myocardial infarction within 30 days prior to the screening examination 5. Patients with a definite diagnosis of active myocarditis or amyloid cardiomyopathy 6. Subjects with any of the following complications or symptoms: * 1\. Poorly controlled diabetes melllitus， * 2\. Anuria， * 3\. Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause 7. Subjects with any of the following disease histories: * 1\. Sustained ventricular tachycardia or ventricular fibrillation within 30 days prior to the screening examination in subjects without an implanted defibrillator， * 2\. Cerebrovascular disorder within 6 months prior to the screening examination (other than asymptomatic cerebral infarction)， * 3\. A history of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride. 8. Subjects who are severely obese \[body mass index (BMI, body weight (kg)/height (m)2\] exceeding 35\] 9. Subjects with systolic blood pressure in the decubitus position exceeding 90 mmHg 10. Subjects with any of the following abnormal laboratory values: * 1\. Total bilirubin \> 3.0 mg/dL, * 2\. serum creatinine \> 3.0 mg/dL, * 3\. serum sodium \> 147 mEq/L, * 4\. serum potassium \> 5.5 mEq/L 11. Patients who are unable to take oral medication 12. Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant during the study period 13. Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination 14. Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight | Baseline, Day 14 or at the time of final drug administration | The change of body weight from baseline at final observation |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stopped at End of Treatment Period 1 Administration of OPC-41061 at 15 mg/day (treatment period 1) for 7 days | 36 |
| Continued at 15 mg/Day Subsequent 7-day repeated administration of OPC-41061 at 15 mg/day (treatment period 2) | 13 |
| Dose Escalated to 30 mg/Day Subsequent 7-day repeated administration of OPC-41061 at 30 mg/day (treatment period 2) | 2 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Rsolution of congenitive symptoms | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Continued at 15 mg/Day | Dose Escalated to 30 mg/Day | Stopped at End of Treatment Period 1 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 2 Participants | 29 Participants | 40 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 0 Participants | 7 Participants | 11 Participants |
| Age, Continuous | 67.2 years STANDARD_DEVIATION 12.7 | 78.5 years STANDARD_DEVIATION 2.1 | 71.3 years STANDARD_DEVIATION 9.5 | 70.5 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment Japan | 13 participants | 2 participants | 36 participants | 51 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 11 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 1 Participants | 25 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 36 | 12 / 13 | 2 / 2 |
| serious Total, serious adverse events | 3 / 36 | 1 / 13 | 0 / 2 |
Outcome results
Primary
Body Weight
The change of body weight from baseline at final observation
Time frame: Baseline, Day 14 or at the time of final drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stopped at End of Treatment Period 1 | Body Weight | -2.05 Kg | Standard Deviation 1.86 |
| Continued at 15 mg/Day | Body Weight | -1.31 Kg | Standard Deviation 2.95 |
| Dose Escalated to 30 mg/Day | Body Weight | -2.9 Kg | Standard Deviation 2.69 |