Edema, Cardiac
Conditions
Keywords
Cardiac edema, OPC-41061, Vasopressin antagonist
Brief summary
To evaluate the efficacy and safety of 7-day repeated oral administration of OPC-41061 15 mg or placebo in congestive heart failure (CHF) patients with extracellular volume expansion despite the use of a conventional diuretic.
Interventions
0, 15mg of OPC-41061 per day for 7days p.o. administration
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects receiving one of the following diuretic treatments (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) 2. CHF patients with lower limb edema, jugular venous distention, or pulmonary congestion due to extracellular volume expansion Patients with pulmonary congestion can be enrolled if pulmonary congestion is confirmed on chest x-ray taken within 14 days prior to the screening examination. 3. Male or female subjects age 20 or older and younger than 85 (at time of informed consent) 4. Subjects who are able to stay at the study site from the day before the start of the run-in observation period until completion of postdosing examination 2 (7 to 10 days after final study drug administration) 5. Subjects capable of giving informed consent to participate in the study of their own free will
Exclusion criteria
1. Subjects with acute heart failure 2. Subjects with an assisted circulation device 3. Subjects 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. Subjects who develop acute myocardial infarction within 30 days prior to the screening examination 5. Subjects with a definite diagnosis of active myocarditis or amyloid cardiomyopathy 6. Subjects with any of the following complications or symptoms: (1)Diabetes mellitus with poorly controlled blood glucose, (2)Anuria, (3)Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause 7. Subjects with a history of any of the following diseases: (1)Sustained ventricular tachycardia or ventricular fibrillation within 30 days prior to the screening examination in patients without an implanted defibrillator, (2)Cerebrovascular disorder within 6 months prior to the screening examination (other than asymptomatic cerebral infarction), (3)Hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride. 8. Subjects who are obese \[body mass index (BMI, body weight (kg)/height (m)2 exceeding 35\] 9. Patients with supine systolic blood pressure exceeding 90 mmHg 10. Subjects with any of following abnormal laboratory values: (1)Total bilirubin exceeding 3.0 mg/dL, (2)serum creatinine exceeding 3.0 mg/dL, (3)serum sodium exceeding 147 mEq/L, (4)serum potassium exceeding 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 13. Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination 14. Subjects who previously participated in this or any other study of OPC-41061 and received OPC-41061 15. 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 (Amount of Change) | baseline, Day 7 or at the time of final trial drug administration | Change in body weight from baseline at the time of final trial drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight (Percent Change) | baseline, Day 7 or at the time of final trial drug administration | Percent change in body weight from baseline at the time of final trial drug administration |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 0 mg of OPC-41061 per day for 7days p.o. administration | 57 |
| OPC-41061 15mg of OPC-41061 per day for 7days p.o. administration | 53 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Resolution of signs and symptoms | 0 | 2 |
Baseline characteristics
| Characteristic | OPC-41061 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 38 Participants | 79 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 19 Participants | 31 Participants |
| Age, Continuous | 71.3 years STANDARD_DEVIATION 10.6 | 71.0 years STANDARD_DEVIATION 10.9 | 71.2 years STANDARD_DEVIATION 10.7 |
| Region of Enrollment Japan | 53 participants | 57 participants | 110 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 35 Participants | 39 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 57 | 28 / 53 |
| serious Total, serious adverse events | 7 / 57 | 2 / 53 |
Outcome results
Primary
Body Weight (Amount of Change)
Change in body weight from baseline at the time of final trial drug administration
Time frame: baseline, Day 7 or at the time of final trial drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Body Weight (Amount of Change) | -0.45 Kg | Standard Deviation 0.93 |
| OPC-41061 15mg | Body Weight (Amount of Change) | -1.54 Kg | Standard Deviation 1.61 |
p-value: <0.000195% CI: [-1.58, -0.6]t-test, 2 sided
Secondary
Body Weight (Percent Change)
Percent change in body weight from baseline at the time of final trial drug administration
Time frame: baseline, Day 7 or at the time of final trial drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Body Weight (Percent Change) | -0.77 percentage of body weight (Kg) | Standard Deviation 1.65 |
| OPC-41061 15mg | Body Weight (Percent Change) | -2.50 percentage of body weight (Kg) | Standard Deviation 2.55 |
p-value: <0.000195% CI: [-2.54, -0.92]t-test, 2 sided