Congestive Heart Failure
Conditions
Brief summary
To confirm the tolerability of intravenous administration of OPC-61815 at 8 or 16 mg once daily for a maximum of 5 days to CHF patients with volume overload despite having received diuretics (injection) other than vasopressin antagonists and who have difficulty with or are incapable of oral intake.
Interventions
Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria.
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
* Patients receiving loop diuretic injection at a dose equivalent to furosemide 20 mg/day or higher * CHF patients in whom lower limb edema, pulmonary congestion, and/or jugular venous distension due to volume overload is present * Patients who are judged by the investigator or subinvestigator to have difficulty or be incapable of oral intake, including patients who are judged by the investigator or subinvestigator to require nothing by mouth(NPO) management * Patients who are currently hospitalized or who are capable of being hospitalized from the time of informed consent until the end of the treatment period * Patients who are capable of giving informed consent
Exclusion criteria
* Patients who are on a ventricular assist device * Patients who have difficulty with spontaneous respiration or who have been on tracheal intubation under sedative therapy * Patients with severe disturbed consciousness (ie, coma or stupor)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | From the start of IMP administration (Day 1) up to 15 days | An AE is defined as any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an AE that leads to death, is life-threatening, results in persistent or significant disability/incapacity, requires in-patient or prolonged hospitalization, results in a congenital anomaly/birth defect, or any other important medical event which is medically significant. A TEAE is an AE that occurs only after a subject has received IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight | Baseline, Day after final IMP administration | Change in body weight from baseline (before IMP administration on Day 1) at time of final IMP administration (day after final IMP administration). A negative change from baseline indicates improvement. |
| Improvement Rate for Lower Limb Edema | Baseline, Day after final IMP administration | The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated |
| Improvement Rate for Pulmonary Congestion | Baseline, Day after final IMP administration | The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated |
Countries
Japan
Participant flow
Pre-assignment details
A total of 45 subjects were administered investigational medicinal product (IMP): 38 subjects with dose maintained at 8 mg, and 7 subjects with dose increased to 16 mg. None of the subjects reduced the dose after the dose was increased to 16 mg. All 45 subjects received at least one dose of IMP and thus were included in the safety analysis set. Overall, 41 subjects completed the trial (34 of those subjects completed the trial early), and 4 subjects were discontinued from the trial.
Participants by arm
| Arm | Count |
|---|---|
| OPC-61815 Injection Intravenous administration of OPC-61815 at 8 mg or 16 mg once daily for a maximum of 5 days. Starting with 8mg, increase the dose to 16mg on Day 2 or Day 3, according to the dose escalation criteria. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Not related to medical events | 1 |
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | OPC-61815 Injection |
|---|---|
| Age, Continuous | 73.7 years STANDARD_DEVIATION 11.1 |
| Race/Ethnicity, Customized Asian | 45 Participants |
| Region of Enrollment Japan | 45 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 7 |
| other Total, other adverse events | 22 / 38 | 2 / 7 |
| serious Total, serious adverse events | 2 / 38 | 0 / 7 |
Outcome results
Primary
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE is defined as any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an AE that leads to death, is life-threatening, results in persistent or significant disability/incapacity, requires in-patient or prolonged hospitalization, results in a congenital anomaly/birth defect, or any other important medical event which is medically significant. A TEAE is an AE that occurs only after a subject has received IMP.
Time frame: From the start of IMP administration (Day 1) up to 15 days
Population: Safety Analysis Set: subjects who received at least one dose of IMP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-61815 Injection | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | 77.8 percentage of participants |
Secondary
Change From Baseline in Body Weight
Change in body weight from baseline (before IMP administration on Day 1) at time of final IMP administration (day after final IMP administration). A negative change from baseline indicates improvement.
Time frame: Baseline, Day after final IMP administration
Population: Subjects with both baseline and evaluation of the given parameter at the specific visit.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| OPC-61815 Injection | Change From Baseline in Body Weight | -3.01 kg |
Secondary
Improvement Rate for Lower Limb Edema
The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated
Time frame: Baseline, Day after final IMP administration
Population: Efficacy Analysis Set: subjects who received at least one dose of IMP and had at least one postbaseline dose efficacy measurement.~Overall Number of Participants Analyzed = number of subjects with baseline symptoms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-61815 Injection | Improvement Rate for Lower Limb Edema | 73.7 percentage of participants |
Secondary
Improvement Rate for Pulmonary Congestion
The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated
Time frame: Baseline, Day after final IMP administration
Population: Efficacy Analysis Set: subjects who received at least one dose of IMP and had at least one postbaseline dose efficacy measurement.~Overall Number of Participants Analyzed = number of subjects with baseline symptoms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-61815 Injection | Improvement Rate for Pulmonary Congestion | 81.8 percentage of participants |