Cardiac Edema (CHF)
Conditions
Brief summary
To investigate the dose response in respect of weight decrease following repeated oral administration of OPC-131461 at 1, 2, 5, and 10 mg or placebo in patients with CHF with volume overload despite having received diuretics other than vasopressin antagonists
Interventions
DRUGOPC 131461 10mg group
OPC-131461 5 mg tablet x 2，once-daily oral administration for 14 days
DRUGOPC 131461 5mg group
OPC-131461 5 mg tablet and placebo tablet，once-daily oral administration for 14 days
DRUGOPC 131461 2mg group
OPC-131461 1 mg tablet x 2，once-daily oral administration for 14 days
DRUGOPC 131461 1mg group
OPC-131461 1 mg tablet and placebo tablet，once-daily oral administration for 14 days
DRUGPlacebo
Placebo tablet，once-daily oral administration for 14 days
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
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with CHF with lower limb edema, pulmonary congestion, or jugular venous distension due to volume overload. * Subjects undergoing any of the following diuretic therapies * Loop diuretics at a dosage equivalent to 40 mg/day or more of furosemide tablet/fine granule * Concomitant administration of a loop diuretic and a thiazide diuretic (including similar drugs) at any doses * Concomitant administration of a loop diuretic and a mineralocorticoid receptor antagonist or potassium-sparing diuretic at any doses * Subjects who were currently hospitalized or who are able to be hospitalized
Exclusion criteria
* Subjects with acute heart failure * Subjects with an assisted circulation device * Subjects who cannot sense thirst or who have difficulty in ingesting water
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8 | Baseline, Day 8 | Calculate the change in body weight from the baseline up to Day 8 (kg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15 | Baseline, Day15 | Calculate the percentage change in body weight from the baseline up to last assessment time point (the day after IMP administration) by Day 15 （％） |
| Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | Baseline, Day7 | The tibial margins or acrotarsia in a sitting position will be examined to assess the severity of edema according to the criteria in 0 : Absent, No pitting observed at all, 1:Mild,Slight pitting observed, 2:Moderate, Pitting observed, 3 : Severe,Apparent edema. Improvement rates (percentages of subjects who have symptoms at baseline and show markedly improved or improved after IMP administration) and resolution rates (percentages of subjects who have symptoms at baseline and no symptoms after IMP administration) at the last assessment time point (the day of IMP administration) by Day 7. |
| Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | Baseline, Day7 | The severity of pulmonary congestion will be determined according to the criteria in 0 : Absent, No congestion, 1:Mild,Pulmonary venous congestion, 2:Moderate, Interstitial pulmonary edema, 3 : Severe, Alveolar pulmonary edema. Improvement rates (percentages of subjects who have symptoms at baseline and show markedly improved or improved after IMP administration) and resolution rates (percentages of subjects who have symptoms at baseline and no symptoms after IMP administration) at the last assessment time point (the day of IMP administration) by Day 7. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Material A OPC 131461 10mg group | 31 |
| Material B OPC 131461 5mg group | 32 |
| Material C OPC 131461 2mg group | 31 |
| Material D OPC 131461 1mg group | 33 |
| Placebo Placebo | 30 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 4 | 3 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 4 | 1 | 3 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Material B | Material C | Material D | Material A | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 28 Participants | 30 Participants | 25 Participants | 25 Participants | 135 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 3 Participants | 3 Participants | 6 Participants | 5 Participants | 22 Participants |
| Age, Continuous | 75.2 Years STANDARD_DEVIATION 10.7 | 75.3 Years STANDARD_DEVIATION 13.1 | 76.7 Years STANDARD_DEVIATION 7.9 | 73.5 Years STANDARD_DEVIATION 11.6 | 76.4 Years STANDARD_DEVIATION 9.4 | 75.4 Years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 32 Participants | 31 Participants | 33 Participants | 31 Participants | 30 Participants | 157 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 2 Participants | 11 Participants | 14 Participants | 12 Participants | 58 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 22 Participants | 17 Participants | 18 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 32 | 0 / 31 | 1 / 33 | 1 / 30 |
| other Total, other adverse events | 11 / 31 | 8 / 32 | 12 / 31 | 14 / 33 | 8 / 30 |
| serious Total, serious adverse events | 0 / 31 | 2 / 32 | 0 / 31 | 1 / 33 | 1 / 30 |
Outcome results
Primary
Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8
Calculate the change in body weight from the baseline up to Day 8 (kg)
Time frame: Baseline, Day 8
Population: The full analysis set includes all subjects who have been administered at least one treatment of the IMP, and for whom efficacy data after IMP administration are available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Material A | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8 | -1.96 kg |
| Material B | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8 | -1.74 kg |
| Material C | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8 | -1.4 kg |
| Material D | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8 | -1.84 kg |
| Placebo | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8 | -1.17 kg |
Secondary
Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15
Calculate the percentage change in body weight from the baseline up to last assessment time point (the day after IMP administration) by Day 15 （％）
Time frame: Baseline, Day15
Population: The full analysis set includes all subjects who have been administered at least one treatment of the IMP, and for whom efficacy data after IMP administration are available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Material A | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15 | -2.12 kg |
| Material B | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15 | -2.11 kg |
| Material C | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15 | -1.72 kg |
| Material D | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15 | -1.87 kg |
| Placebo | Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15 | -1.38 kg |
Secondary
Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7
The tibial margins or acrotarsia in a sitting position will be examined to assess the severity of edema according to the criteria in 0 : Absent, No pitting observed at all, 1:Mild,Slight pitting observed, 2:Moderate, Pitting observed, 3 : Severe,Apparent edema. Improvement rates (percentages of subjects who have symptoms at baseline and show markedly improved or improved after IMP administration) and resolution rates (percentages of subjects who have symptoms at baseline and no symptoms after IMP administration) at the last assessment time point (the day of IMP administration) by Day 7.
Time frame: Baseline, Day7
Population: The full analysis set includes all subjects who have been administered at least one treatment of the IMP, and for whom efficacy data after IMP administration are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Material A | Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 16 Participants |
| Material B | Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 18 Participants |
| Material C | Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 9 Participants |
| Material D | Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 19 Participants |
| Placebo | Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 19 Participants |
Secondary
Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7
The severity of pulmonary congestion will be determined according to the criteria in 0 : Absent, No congestion, 1:Mild,Pulmonary venous congestion, 2:Moderate, Interstitial pulmonary edema, 3 : Severe, Alveolar pulmonary edema. Improvement rates (percentages of subjects who have symptoms at baseline and show markedly improved or improved after IMP administration) and resolution rates (percentages of subjects who have symptoms at baseline and no symptoms after IMP administration) at the last assessment time point (the day of IMP administration) by Day 7.
Time frame: Baseline, Day7
Population: The full analysis set includes all subjects who have been administered at least one treatment of the IMP, and for whom efficacy data after IMP administration are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Material A | Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 21 Participants |
| Material B | Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 19 Participants |
| Material C | Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 10 Participants |
| Material D | Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 22 Participants |
| Placebo | Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7 | 18 Participants |