Hyponatremia
Conditions
Keywords
hyponatremia, hypervolemic, euvolemic, edematous, conivaptan
Brief summary
The study is designed to assess the efficacy and safety of multiple infusions of conivaptan in subjects with euvolemic or hypervolemic hyponatremia
Interventions
DRUGConivaptan
premix bag
DRUGPlacebo
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
* Euvolemic or hypervolemic (edematous) based on clinical presentation * Serum sodium between 115 and 130mEq/L at baseline
Exclusion criteria
* Clinical presentation of volume depletion or dehydration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Baseline and 48 hours | Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Hour 48 - Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium | 48 Hours | Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. The endpoint was not evaluable in the placebo arm (median and interquartile range cannot be estimated) or the conivaptan QD arm (interquartile range cannot be estimated) because too high a percentage of patients were censored for the event. Only the conivaptan BID arm will be reported. |
| Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours | 48 Hours | Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. |
| Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours | 48 Hours | Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>6 mEq/L or two consecutive measurements \>135 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. |
| Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48 | Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline |
| Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Baseline, Hour 12, Hour 24,Hour 36 and Hour 48 | Effective water clearence (EWC) was calculated as EWC=V(1-(Una+Uk)/(Pna+Pk)), where V is urine volume, Una is the urine sodium concentration, Uk is the urine potassium concentration, Pna is the serum/plasma sodium concentration, an Pk is the serum /plasma potassium concentration. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline |
| Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Baseline, Hour 24 and Hour 48 | Free water clearance (FWC) was calculated as FWC=V(1-Uosm/Posm), where V is urine volume, Uosm is the urine osmolality, Posm is the plasma sodium osmolality. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline |
| Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours | 48 Hours | Each individual subject's change from baseline serum sodium levels was used to calculate baseline adjusted area under the curve serum sodium levels for a duration of Time 0 to Time t in hours (labeled as AUC(Na)(0-t). The last available serum sodium level prior to dosing on Day 1 was used as baseline. t=48 Hours |
Countries
India, United States
Participant flow
Pre-assignment details
One patient in the Placebo arm discontinued prior to dosing and therefore was not included in the Full Analysis Set (FAS) or the Safety Analysis Set (SAF).
Participants by arm
| Arm | Count |
|---|---|
| Regimen 1 Conivaptan QD 20 mg conivaptan once a day | 20 |
| Regimen 2 Conivaptan BID 20 mg conivaptan two times a day | 20 |
| Regimen 3 Placebo | 9 |
| Total | 49 |
Baseline characteristics
| Characteristic | Regimen 1 Conivaptan QD | Regimen 2 Conivaptan BID | Regimen 3 Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 17.36 | 67.5 years STANDARD_DEVIATION 14.7 | 61.8 years STANDARD_DEVIATION 20.19 | 62.8 years STANDARD_DEVIATION 17.01 |
| Race/Ethnicity, Customized Asian | 7 participants | 4 participants | 3 participants | 14 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 1 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized White | 12 participants | 15 participants | 4 participants | 31 participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Male | 13 Participants | 9 Participants | 1 Participants | 23 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 | 7 / 20 | 10 / 20 | 5 / 9 |
| serious Total, serious adverse events | 6 / 20 | 5 / 20 | 2 / 9 |
Outcome results
Primary
Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Hour 48 - Baseline.
Time frame: Baseline and 48 hours
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.~The number of participants analyzed per arm represents FAS. The numbers of participants for each visit are noted in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan QD | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Hour 48 (N=19; 17; 8) | 130.4 mEq/L | Standard Deviation 5.21 |
| Regimen 1 Conivaptan QD | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Baseline (N= 20; 20; 9) | 126.03 mEq/L | Standard Deviation 4.017 |
| Regimen 1 Conivaptan QD | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Change from Baseline (N=19; 17; 8) | 4.00 mEq/L | Standard Deviation 3.8 |
| Regimen 2 Conivaptan BID | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Hour 48 (N=19; 17; 8) | 133.4 mEq/L | Standard Deviation 4.82 |
| Regimen 2 Conivaptan BID | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Baseline (N= 20; 20; 9) | 126.39 mEq/L | Standard Deviation 3.581 |
| Regimen 2 Conivaptan BID | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Change from Baseline (N=19; 17; 8) | 7.36 mEq/L | Standard Deviation 4.04 |
| Regimen 3 Placebo | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Baseline (N= 20; 20; 9) | 125.55 mEq/L | Standard Deviation 3.648 |
| Regimen 3 Placebo | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Change from Baseline (N=19; 17; 8) | 1.16 mEq/L | Standard Deviation 2.86 |
| Regimen 3 Placebo | Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. | Hour 48 (N=19; 17; 8) | 127.6 mEq/L | Standard Deviation 2.36 |
Comparison: Statistical Analysis applies to Change from Baseline.p-value: 0.028ANCOVA
Comparison: Statistical Analysis applies to Change from Baseline.p-value: 0.019ANCOVA
Comparison: Statistical Analysis applies to Change from Baseline.p-value: <0.001ANCOVA
Secondary
Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours
Each individual subject's change from baseline serum sodium levels was used to calculate baseline adjusted area under the curve serum sodium levels for a duration of Time 0 to Time t in hours (labeled as AUC(Na)(0-t). The last available serum sodium level prior to dosing on Day 1 was used as baseline. t=48 Hours
Time frame: 48 Hours
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen 1 Conivaptan QD | Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours | 142.72 Hour * mEq/L | Standard Deviation 132.94 |
| Regimen 2 Conivaptan BID | Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours | 244.17 Hour * mEq/L | Standard Deviation 142.64 |
| Regimen 3 Placebo | Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours | 23.21 Hour * mEq/L | Standard Deviation 91.49 |
p-value: 0.079ANCOVA
Secondary
Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment
Effective water clearence (EWC) was calculated as EWC=V(1-(Una+Uk)/(Pna+Pk)), where V is urine volume, Una is the urine sodium concentration, Uk is the urine potassium concentration, Pna is the serum/plasma sodium concentration, an Pk is the serum /plasma potassium concentration. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline
Time frame: Baseline, Hour 12, Hour 24,Hour 36 and Hour 48
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.~The number of participants analyzed per arm represents FAS. The numbers of participants for each visit are noted in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 24 (N=14; 12; 6) | -50.19 mL | Standard Deviation 794.22 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 48 (N=12; 10; 4) | 80.23 mL | Standard Deviation 1116.99 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 36 (N=15; 11; 6) | 36.85 mL | Standard Deviation 905.18 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 24 (N=13; 11; 5) | -70.61 mL | Standard Deviation 796.01 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Baseline (N=16; 12; 6) | 6.76 mL | Standard Deviation 47.91 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 48 (N=14; 11; 5) | -77.37 mL | Standard Deviation 1169.3 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 12 (N=12;12; 4) | 301.52 mL | Standard Deviation 671.78 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 12 (N=14; 12; 5) | 355.65 mL | Standard Deviation 684.35 |
| Regimen 1 Conivaptan QD | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 36 (N=12; 8; 5) | -91.07 mL | Standard Deviation 912.66 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 24 (N=13; 11; 5) | -391.76 mL | Standard Deviation 1206.39 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Baseline (N=16; 12; 6) | 39.86 mL | Standard Deviation 245.23 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 12 (N=14; 12; 5) | 405.21 mL | Standard Deviation 744.88 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 12 (N=12;12; 4) | 365.35 mL | Standard Deviation 699.96 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 24 (N=14; 12; 6) | -261.27 mL | Standard Deviation 1009.24 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 36 (N=15; 11; 6) | 12.66 mL | Standard Deviation 743.24 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 36 (N=12; 8; 5) | -89.12 mL | Standard Deviation 805.36 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 48 (N=14; 11; 5) | -179.37 mL | Standard Deviation 852.58 |
| Regimen 2 Conivaptan BID | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 48 (N=12; 10; 4) | -240.39 mL | Standard Deviation 759.82 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 12 (N=12;12; 4) | 135.44 mL | Standard Deviation 123.36 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Baseline (N=16; 12; 6) | 18.66 mL | Standard Deviation 45.05 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 36 (N=12; 8; 5) | 810.45 mL | Standard Deviation 1079.89 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 12 (N=14; 12; 5) | 136.22 mL | Standard Deviation 154.94 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 48 (N=12; 10; 4) | 690.98 mL | Standard Deviation 2872.2 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 24 (N=13; 11; 5) | 383.73 mL | Standard Deviation 723.33 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 24 (N=14; 12; 6) | 368.01 mL | Standard Deviation 688.81 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 48 (N=14; 11; 5) | 569.09 mL | Standard Deviation 1392.07 |
| Regimen 3 Placebo | Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment | Hour 36 (N=15; 11; 6) | 726.96 mL | Standard Deviation 1013.78 |
Secondary
Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment
Free water clearance (FWC) was calculated as FWC=V(1-Uosm/Posm), where V is urine volume, Uosm is the urine osmolality, Posm is the plasma sodium osmolality. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline
Time frame: Baseline, Hour 24 and Hour 48
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.~The number of participants analyzed per arm represents FAS. The numbers of participants for each visit are noted in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan QD | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Hour 48 (N=14;12; 5) | -1243.39 mL | Standard Deviation 2211.22 |
| Regimen 1 Conivaptan QD | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 24 (N=11; 10; 5) | -936.99 mL | Standard Deviation 1618.46 |
| Regimen 1 Conivaptan QD | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Baseline (N=14; 11; 6) | -53.87 mL | Standard Deviation 45.47 |
| Regimen 1 Conivaptan QD | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Hour 24 (N=14; 12; 6) | -972.29 mL | Standard Deviation 1455.66 |
| Regimen 1 Conivaptan QD | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 48 (N=11; 10; 4) | -1313.98 mL | Standard Deviation 2477.39 |
| Regimen 2 Conivaptan BID | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 24 (N=11; 10; 5) | -513.33 mL | Standard Deviation 566.72 |
| Regimen 2 Conivaptan BID | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Baseline (N=14; 11; 6) | 6.55 mL | Standard Deviation 165.07 |
| Regimen 2 Conivaptan BID | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Hour 24 (N=14; 12; 6) | -611.14 mL | Standard Deviation 693.863 |
| Regimen 2 Conivaptan BID | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Hour 48 (N=14;12; 5) | -769.19 mL | Standard Deviation 934.31 |
| Regimen 2 Conivaptan BID | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 48 (N=11; 10; 4) | -603.67 mL | Standard Deviation 761.9 |
| Regimen 3 Placebo | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 48 (N=11; 10; 4) | -702.11 mL | Standard Deviation 1117.92 |
| Regimen 3 Placebo | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Hour 48 (N=14;12; 5) | -592.96 mL | Standard Deviation 1050.94 |
| Regimen 3 Placebo | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Baseline (N=14; 11; 6) | -34.90 mL | Standard Deviation 74.32 |
| Regimen 3 Placebo | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Change at Hour 24 (N=11; 10; 5) | -420.75 mL | Standard Deviation 747.84 |
| Regimen 3 Placebo | Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment | Hour 24 (N=14; 12; 6) | -416.71 mL | Standard Deviation 666.97 |
Secondary
Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment
Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline
Time frame: Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.~The number of participants analyzed per arm represents FAS. The numbers of participants for each visit are noted in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 40 (N=19; 16; 8) | 4.39 mEq/L | Standard Deviation 3.44 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 12 (N=19; 19; 7) | 1.78 mEq/L | Standard Deviation 3.44 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 16 (N=19; 17; 7) | 2.90 mEq/L | Standard Deviation 3.46 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 40 (N=19; 16; 8) | 130.83 mEq/L | Standard Deviation 5.04 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 4 (N=19; 20; 8) | 1.59 mEq/L | Standard Deviation 2.32 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 48 (N=19; 17; 8) | 130.44 mEq/L | Standard Deviation 5.21 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 36 (N=19; 15; 8) | 4.98 mEq/L | Standard Deviation 3.73 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 24 (N=18; 16; 8) | 2.66 mEq/L | Standard Deviation 3.76 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 16 (N=19; 17; 7) | 129.34 mEq/L | Standard Deviation 4.51 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Baseline (N=20; 20; 9) | 126.03 mEq/L | Standard Deviation 4.02 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 28 (N=19; 17; 8) | 130.79 mEq/L | Standard Deviation 4.94 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 48 (N=19; 17; 8) | 4.00 mEq/L | Standard Deviation 3.8 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 12 (N=19; 19; 7) | 128.22 mEq/L | Standard Deviation 5.27 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 28 (N=19; 17; 8) | 4.35 mEq/L | Standard Deviation 3.8 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 4 (N=19; 20; 8) | 128.03 mEq/L | Standard Deviation 4.62 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 24 (N=18; 16; 8) | 128.87 mEq/L | Standard Deviation 4.73 |
| Regimen 1 Conivaptan QD | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 36 (N=19; 15; 8) | 131.42 mEq/L | Standard Deviation 4.99 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 16 (N=19; 17; 7) | 131.04 mEq/L | Standard Deviation 5.07 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 36 (N=19; 15; 8) | 6.54 mEq/L | Standard Deviation 3.28 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 40 (N=19; 16; 8) | 132.23 mEq/L | Standard Deviation 3.99 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 12 (N=19; 19; 7) | 4.65 mEq/L | Standard Deviation 4.06 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 40 (N=19; 16; 8) | 6.30 mEq/L | Standard Deviation 3.27 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 4 (N=19; 20; 8) | 128.47 mEq/L | Standard Deviation 4.21 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 48 (N=19; 17; 8) | 133.35 mEq/L | Standard Deviation 4.82 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 48 (N=19; 17; 8) | 7.36 mEq/L | Standard Deviation 4.04 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 36 (N=19; 15; 8) | 132.47 mEq/L | Standard Deviation 5.04 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Baseline (N=20; 20; 9) | 126.39 mEq/L | Standard Deviation 3.58 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 16 (N=19; 17; 7) | 4.93 mEq/L | Standard Deviation 3.28 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 24 (N=18; 16; 8) | 130.74 mEq/L | Standard Deviation 5.33 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 4 (N=19; 20; 8) | 2.08 mEq/L | Standard Deviation 2.65 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 24 (N=18; 16; 8) | 4.62 mEq/L | Standard Deviation 3.59 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 28 (N=19; 17; 8) | 131.62 mEq/L | Standard Deviation 4.52 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 28 (N=19; 17; 8) | 5.51 mEq/L | Standard Deviation 2.75 |
| Regimen 2 Conivaptan BID | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 12 (N=19; 19; 7) | 130.85 mEq/L | Standard Deviation 5.88 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 48 (N=19; 17; 8) | 1.16 mEq/L | Standard Deviation 2.86 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Baseline (N=20; 20; 9) | 125.55 mEq/L | Standard Deviation 3.65 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 4 (N=19; 20; 8) | 125.80 mEq/L | Standard Deviation 4.63 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 4 (N=19; 20; 8) | -0.63 mEq/L | Standard Deviation 2.77 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 12 (N=19; 19; 7) | 127.21 mEq/L | Standard Deviation 5.24 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 12 (N=19; 19; 7) | 0.73 mEq/L | Standard Deviation 3.92 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 16 (N=19; 17; 7) | 127.57 mEq/L | Standard Deviation 3.78 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 16 (N=19; 17; 7) | 1.09 mEq/L | Standard Deviation 2.69 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 24 (N=18; 16; 8) | 127.48 mEq/L | Standard Deviation 3.62 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 24 (N=18; 16; 8) | 1.05 mEq/L | Standard Deviation 2.73 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 28 (N=19; 17; 8) | 126.49 mEq/L | Standard Deviation 4.03 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 28 (N=19; 17; 8) | 0.06 mEq/L | Standard Deviation 3.3 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 36 (N=19; 15; 8) | 127.31 mEq/L | Standard Deviation 3.05 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 36 (N=19; 15; 8) | 0.89 mEq/L | Standard Deviation 2.55 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 40 (N=19; 16; 8) | 127.00 mEq/L | Standard Deviation 1.85 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Change at Hour 40 (N=19; 16; 8) | 0.58 mEq/L | Standard Deviation 1.66 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment | Hour 48 (N=19; 17; 8) | 127.59 mEq/L | Standard Deviation 2.36 |
Secondary
Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours
Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.
Time frame: 48 Hours
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen 1 Conivaptan QD | Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours | 12 Patients |
| Regimen 2 Conivaptan BID | Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours | 17 Patients |
| Regimen 3 Placebo | Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours | 2 Patients |
Secondary
Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours
Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>6 mEq/L or two consecutive measurements \>135 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.
Time frame: 48 Hours
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen 1 Conivaptan QD | Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours | 6 Patients |
| Regimen 2 Conivaptan BID | Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours | 11 Patients |
| Regimen 3 Placebo | Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours | 0 Patients |
Secondary
Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium
Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. The endpoint was not evaluable in the placebo arm (median and interquartile range cannot be estimated) or the conivaptan QD arm (interquartile range cannot be estimated) because too high a percentage of patients were censored for the event. Only the conivaptan BID arm will be reported.
Time frame: 48 Hours
Population: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regimen 1 Conivaptan QD | Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium | 16.43 Hours |