Hyponatremia, Euvolemia, Hypervolemia
Conditions
Keywords
Hyponatremia, Euvolemia, Hypervolemia, Conivaptan, Vaprisol®, YM087
Brief summary
The study will evaluate the effectiveness and safety of multiple dosing regimens of IV conivaptan in subjects with euvolemic or hypervolemic hyponatremia
Interventions
DRUGConivaptan
ampoule or premix bag
DRUGplacebo
ampoule or premix bag
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a serum sodium value between 115 and 133 mEq/L * Subject is euvolemic or hypervolemic
Exclusion criteria
* Clinical evidence of volume depletion or dehydration * Uncontrolled brady- or tachyarrhythmias requiring emergent pacemaker placement or treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | 48 hours | Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion. One ISRMS has been reported for each participant & represents the most severe state of ISR for that participant. ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment | Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. Change from Baseline is calculated as Time point minus Baseline. |
| Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | 24.5 hours, 48.5 hours and 96.5 hours | AUCna t is calculated as the baseline-adjusted area under serum sodium levels for a duration of time 0 to time t. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. |
| Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period | 48.5 hours | The upper limits of the interquartile range were not estimable in three of the treatment arms. Only the placebo loading dose + YM087 premix continuous infusion arm will be reported. Time is number of hours to reach an increase of exceeding 4 mEq/L from baseline serum sodium. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. |
| Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0-24.5 hours, 0-48.5 hours and 0-96.5 hours | Patients with confirmed serum sodium level exceeding 4 mEq/L increase from baseline. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. |
| Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0-24.5 hours, 0-48.5 hours and 0-96.5 hours | Patients with confirmed serum sodium level exceeding 6 mEq/L increase from baseline or confirmed normal serum sodium level exceeding 135 mEq/L. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. |
Countries
India, Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Regimen 1 Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule | 28 |
| Dose Regimen 2 Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule | 30 |
| Dose Regimen 3 Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag | 30 |
| Dose Regimen 4 Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag | 29 |
| Total | 117 |
Baseline characteristics
| Characteristic | Dose Regimen 1 | Dose Regimen 2 | Dose Regimen 3 | Dose Regimen 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 20.28 | 61.1 years STANDARD_DEVIATION 20.14 | 64.8 years STANDARD_DEVIATION 14.13 | 63.3 years STANDARD_DEVIATION 22.31 | 62.1 years STANDARD_DEVIATION 19.28 |
| Race/Ethnicity, Customized American Indian / Alaskan | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 13 Participants | 15 Participants | 13 Participants | 55 Participants |
| Race/Ethnicity, Customized Black/ African -American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 16 Participants | 14 Participants | 16 Participants | 60 Participants |
| Sex: Female, Male Female | 14 Participants | 13 Participants | 16 Participants | 18 Participants | 61 Participants |
| Sex: Female, Male Male | 14 Participants | 17 Participants | 14 Participants | 11 Participants | 56 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ CHF | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ COPD | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ Idiopathic | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ Malignancy | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ Other | 2 Participants | 7 Participants | 4 Participants | 6 Participants | 19 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ SIADH | 15 Participants | 11 Participants | 11 Participants | 9 Participants | 46 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Euvolemic/ Unknown | 6 Participants | 8 Participants | 8 Participants | 10 Participants | 32 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Hypervolemic/ CHF | 3 Participants | 2 Participants | 0 Participants | 2 Participants | 7 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Hypervolemic/ SIADH | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Volume Status/ Underlying Cause of Hyponatremia Hypervolemic/ Unknown | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 28 | 12 / 30 | 4 / 30 | 8 / 29 |
| serious Total, serious adverse events | 2 / 28 | 5 / 30 | 8 / 30 | 2 / 29 |
Outcome results
Primary
Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2
Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion. One ISRMS has been reported for each participant & represents the most severe state of ISR for that participant. ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis
Time frame: 48 hours
Population: Population is Safety Analysis Set (SAF): All randomized patients who received at least 1 dose of study drug.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Regimen 1 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - No assessment | 0 Participants |
| Dose Regimen 1 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 0 | 17 Participants |
| Dose Regimen 1 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 1+ | 5 Participants |
| Dose Regimen 1 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 2+ | 2 Participants |
| Dose Regimen 1 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 3+ | 4 Participants |
| Dose Regimen 1 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 4+ | 0 Participants |
| Dose Regimen 2 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 3+ | 5 Participants |
| Dose Regimen 2 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - No assessment | 1 Participants |
| Dose Regimen 2 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 2+ | 0 Participants |
| Dose Regimen 2 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 0 | 16 Participants |
| Dose Regimen 2 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 4+ | 1 Participants |
| Dose Regimen 2 | Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 | Infusion Site Reaction - 1+ | 7 Participants |
Comparison: Aggregated data were used to determine differences between groups. Statistical analysis is relevant to the aggregated data of all rows except the no assessment row.95% CI: [-0.37, 0.83]
Secondary
Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours
AUCna t is calculated as the baseline-adjusted area under serum sodium levels for a duration of time 0 to time t. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Time frame: 24.5 hours, 48.5 hours and 96.5 hours
Population: Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Regimen 1 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 24.5 hours | 45.600 hr * mEq/L | Standard Deviation 55.919 |
| Dose Regimen 1 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 96.5 hours | 375.379 hr * mEq/L | Standard Deviation 331.298 |
| Dose Regimen 1 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 48.5 hours | 133.664 hr * mEq/L | Standard Deviation 127.156 |
| Dose Regimen 2 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 24.5 hours | 70.569 hr * mEq/L | Standard Deviation 73.042 |
| Dose Regimen 2 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 96.5 hours | 503.127 hr * mEq/L | Standard Deviation 340.247 |
| Dose Regimen 2 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 48.5 hours | 194.561 hr * mEq/L | Standard Deviation 166.015 |
| Dose Regimen 3 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 48.5 hours | 205.522 hr * mEq/L | Standard Deviation 163.261 |
| Dose Regimen 3 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 24.5 hours | 66.096 hr * mEq/L | Standard Deviation 73.662 |
| Dose Regimen 3 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 96.5 hours | 558.926 hr * mEq/L | Standard Deviation 351.718 |
| Dose Regimen 4 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 24.5 hours | 82.470 hr * mEq/L | Standard Deviation 82.195 |
| Dose Regimen 4 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 96.5 hours | 528.377 hr * mEq/L | Standard Deviation 371.075 |
| Dose Regimen 4 | Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours | AUCna at 48.5 hours | 207.043 hr * mEq/L | Standard Deviation 170.153 |
Secondary
Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period
Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. Change from Baseline is calculated as Time point minus Baseline.
Time frame: Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment
Population: Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data.~The number of participants analyzed per arm represents Full Analysis Set. The numbers of participants for each time point are noted in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Baseline | 124.6 mmol/L | Standard Deviation 3.75 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 4 (N=28; 26; 30; 28) | 1.2 mmol/L | Standard Deviation 3.67 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 6 (N=27; 27; 29; 27) | 1.1 mmol/L | Standard Deviation 1.96 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 10 (N=27; 28; 30; 26) | 2.3 mmol/L | Standard Deviation 2.92 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 16 (N=24; 24; 27; 23) | 2.0 mmol/L | Standard Deviation 2.93 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 24 (N= 27; 27; 30; 24) | 3.3 mmol/L | Standard Deviation 3.23 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 30 (N=27; 28; 28; 23) | 3.1 mmol/L | Standard Deviation 4.13 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 40 (N=24; 26; 26; 24) | 4.3 mmol/L | Standard Deviation 3.01 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 48.5 (N=26; 28; 28; 27) | 4.6 mmol/L | Standard Deviation 4.01 |
| Dose Regimen 1 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Day 7 (N=23; 27; 25; 17) | 6.7 mmol/L | Standard Deviation 5.87 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 6 (N=27; 27; 29; 27) | 2.5 mmol/L | Standard Deviation 2.88 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 48.5 (N=26; 28; 28; 27) | 5.8 mmol/L | Standard Deviation 4.63 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 10 (N=27; 28; 30; 26) | 2.9 mmol/L | Standard Deviation 3.09 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 16 (N=24; 24; 27; 23) | 4.0 mmol/L | Standard Deviation 4.09 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 24 (N= 27; 27; 30; 24) | 4.5 mmol/L | Standard Deviation 3.85 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 30 (N=27; 28; 28; 23) | 4.5 mmol/L | Standard Deviation 3.51 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Day 7 (N=23; 27; 25; 17) | 9.6 mmol/L | Standard Deviation 5.17 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 40 (N=24; 26; 26; 24) | 5.1 mmol/L | Standard Deviation 4.14 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Baseline | 123.5 mmol/L | Standard Deviation 4.08 |
| Dose Regimen 2 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 4 (N=28; 26; 30; 28) | 1.5 mmol/L | Standard Deviation 2.67 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 40 (N=24; 26; 26; 24) | 6.9 mmol/L | Standard Deviation 4.68 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 30 (N=27; 28; 28; 23) | 4.8 mmol/L | Standard Deviation 4.14 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Day 7 (N=23; 27; 25; 17) | 7.2 mmol/L | Standard Deviation 4.22 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Baseline | 124.5 mmol/L | Standard Deviation 3.67 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 10 (N=27; 28; 30; 26) | 2.7 mmol/L | Standard Deviation 3.88 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 24 (N= 27; 27; 30; 24) | 4.4 mmol/L | Standard Deviation 4.43 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 48.5 (N=26; 28; 28; 27) | 6.5 mmol/L | Standard Deviation 4.19 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 4 (N=28; 26; 30; 28) | 0.7 mmol/L | Standard Deviation 2.13 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 16 (N=24; 24; 27; 23) | 4.2 mmol/L | Standard Deviation 3.82 |
| Dose Regimen 3 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 6 (N=27; 27; 29; 27) | 1.5 mmol/L | Standard Deviation 2.7 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 16 (N=24; 24; 27; 23) | 4.8 mmol/L | Standard Deviation 3.9 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 40 (N=24; 26; 26; 24) | 6.1 mmol/L | Standard Deviation 4.52 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 24 (N= 27; 27; 30; 24) | 5.0 mmol/L | Standard Deviation 3.81 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Day 7 (N=23; 27; 25; 17) | 8.9 mmol/L | Standard Deviation 5.11 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 30 (N=27; 28; 28; 23) | 4.1 mmol/L | Standard Deviation 2.81 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 4 (N=28; 26; 30; 28) | 1.9 mmol/L | Standard Deviation 3.92 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 6 (N=27; 27; 29; 27) | 2.7 mmol/L | Standard Deviation 3.23 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 10 (N=27; 28; 30; 26) | 2.9 mmol/L | Standard Deviation 3.4 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Baseline | 124.0 mmol/L | Standard Deviation 4.63 |
| Dose Regimen 4 | Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period | Change at Hour 48.5 (N=26; 28; 28; 27) | 5.4 mmol/L | Standard Deviation 4.37 |
Secondary
Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
Patients with confirmed serum sodium level exceeding 4 mEq/L increase from baseline. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Time frame: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours
Population: Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Regimen 1 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 6 Participants |
| Dose Regimen 1 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 21 Participants |
| Dose Regimen 1 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 13 Participants |
| Dose Regimen 2 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 13 Participants |
| Dose Regimen 2 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 22 Participants |
| Dose Regimen 2 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 15 Participants |
| Dose Regimen 3 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 23 Participants |
| Dose Regimen 3 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 13 Participants |
| Dose Regimen 3 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 27 Participants |
| Dose Regimen 4 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 10 Participants |
| Dose Regimen 4 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 24 Participants |
| Dose Regimen 4 | Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 19 Participants |
Secondary
Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
Patients with confirmed serum sodium level exceeding 6 mEq/L increase from baseline or confirmed normal serum sodium level exceeding 135 mEq/L. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Time frame: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours
Population: Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Regimen 1 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 1 Participants |
| Dose Regimen 1 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 13 Participants |
| Dose Regimen 1 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 6 Participants |
| Dose Regimen 2 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 6 Participants |
| Dose Regimen 2 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 16 Participants |
| Dose Regimen 2 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 13 Participants |
| Dose Regimen 3 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 17 Participants |
| Dose Regimen 3 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 7 Participants |
| Dose Regimen 3 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 24 Participants |
| Dose Regimen 4 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 24.5 Hours | 6 Participants |
| Dose Regimen 4 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 96.5 Hours | 19 Participants |
| Dose Regimen 4 | Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours | 0 - 48.5 Hours | 12 Participants |
Secondary
Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period
The upper limits of the interquartile range were not estimable in three of the treatment arms. Only the placebo loading dose + YM087 premix continuous infusion arm will be reported. Time is number of hours to reach an increase of exceeding 4 mEq/L from baseline serum sodium. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Time frame: 48.5 hours
Population: Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Regimen 1 | Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period | 24.08 Hours |