Liver Cirrhosis
Conditions
Keywords
conivaptan, Liver Cirrhosis, Hypertension, Portal
Brief summary
To evaluate the safety of IV conivaptan in stable euvolemic or hypervolemic cirrhotic patients, and to characterize the effects of IV conivaptan on the hepatic hemodynamic response in patients with cirrhosis.
Interventions
DRUGconivaptan
IV
DRUGPlacebo
IV
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
* Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written Informed Consent and appropriate privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable) * Subject is euvolemic or hypervolemic (edematous) secondary to cirrhosis * Subject has clinical evidence of portal hypertension by the presence of esophageal varices, ascites or both
Exclusion criteria
* Clinical evidence of volume depletion or dehydration * Subject has a history of bleeding from esophageal varices within three months before the start of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Baseline and 0.5, 1, and 1.5 hours post dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. |
| Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Baseline and 0.5, 1, and 1.5 hours post dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. |
| Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Baseline and 0.5, 1, and 1.5 hours post dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. |
| Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. |
| Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Baseline and 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 hours and on Day 8 post dose | Baseline serum sodium value is the last measurement prior to dosing. Change from baseline is calculated as time point minus baseline. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Regimen 1 Conivaptan 12.5 mg Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours | 6 |
| Regimen 2 Conivaptan 25 mg Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours | 9 |
| Regimen 3 Placebo Placebo continuous intravenous infusion over 6.5 hours | 5 |
| Total | 20 |
Baseline characteristics
| Characteristic | Total | Regimen 1 Conivaptan 12.5 mg | Regimen 3 Placebo | Regimen 2 Conivaptan 25 mg |
|---|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 8.95 | 63.7 years STANDARD_DEVIATION 8.52 | 55.2 years STANDARD_DEVIATION 7.19 | 60.0 years STANDARD_DEVIATION 9.72 |
| Race/Ethnicity, Customized White | 20 Participants | 6 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 15 Participants | 3 Participants | 5 Participants | 7 Participants |
| Underlying Cause of Hyponatremia Euvolemic - Cirrhosis | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Underlying Cause of Hyponatremia Euvolemic - Not Hyponatremia | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Underlying Cause of Hyponatremia Euvolemic - Other | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Underlying Cause of Hyponatremia Hypervolemic - Cirrhosis | 8 Participants | 2 Participants | 3 Participants | 3 Participants |
| Underlying Cause of Hyponatremia Hypervolemic - Not Hyponatremia | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Underlying Cause of Hyponatremia Hypervolemic - Other | 1 Participants | 0 Participants | 0 Participants | 1 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 | 1 / 6 | 6 / 9 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 2 / 9 | 0 / 5 |
Outcome results
Primary
Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Time frame: Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose
Population: Population is Safety Analysis Set (SAF): All randomized patients who received at least one dose of study medication.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 9 Hours | -5.5 mmHg | Standard Deviation 15.35 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 1 Hour | 5.5 mmHg | Standard Deviation 17.62 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 24 Hours | -10.8 mmHg | Standard Deviation 15.21 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 24 Hours | -0.5 mmHg | Standard Deviation 7.34 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 3.5 Hours | -6.0 mmHg | Standard Deviation 8.94 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 8 Days | -11.5 mmHg | Standard Deviation 7.87 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 6.5 Hours | -8.8 mmHg | Standard Deviation 10.65 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 9 Hours | 5.0 mmHg | Standard Deviation 5.62 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Baseline | 60.3 mmHg | Standard Deviation 10.65 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 8 Days | -3.0 mmHg | Standard Deviation 6.72 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 1.5 Hours | 7.8 mmHg | Standard Deviation 20.9 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 0.5 Hours | 4.5 mmHg | Standard Deviation 3.27 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 6.5 Hours | -1.0 mmHg | Standard Deviation 7.13 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 4.5 Hours | -6.2 mmHg | Standard Deviation 12.91 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 1 Hour | 7.3 mmHg | Standard Deviation 5.57 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 2.5 Hours | -2.5 mmHg | Standard Deviation 9.65 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Baseline | 112.2 mmHg | Standard Deviation 13.73 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 1.5 Hours | 9.2 mmHg | Standard Deviation 5.04 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 12 Hours | 0.0 mmHg | Standard Deviation 12.68 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 12 Hours | -14.0 mmHg | Standard Deviation 21.48 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 2.5 Hours | 2.2 mmHg | Standard Deviation 4.83 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 0.5 Hours | 5.3 mmHg | Standard Deviation 13.29 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 5.5 Hours | -6.3 mmHg | Standard Deviation 7.2 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 3.5 Hours | 1.0 mmHg | Standard Deviation 2.28 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 5.5 Hours | 2.7 mmHg | Standard Deviation 3.93 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 4.5 Hours | -2.5 mmHg | Standard Deviation 3.27 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 5.5 Hours | -8.7 mmHg | Standard Deviation 14.94 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 4.5 Hours | -6.3 mmHg | Standard Deviation 7.45 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 1 Hour | 13.9 mmHg | Standard Deviation 14.12 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 5.5 Hours | -4.2 mmHg | Standard Deviation 7.79 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 6.5 Hours | -4.7 mmHg | Standard Deviation 6.2 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 6.5 Hours | -9.7 mmHg | Standard Deviation 7.73 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 9 Hours | 0.3 mmHg | Standard Deviation 4.82 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 12 Hours | -3.3 mmHg | Standard Deviation 6.42 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 24 Hours | -5.1 mmHg | Standard Deviation 5.56 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 9 Hours | 1.9 mmHg | Standard Deviation 11.46 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 8 Days | -5.0 mmHg | Standard Deviation 9.55 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 2.5 Hours | -3.8 mmHg | Standard Deviation 8.15 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Baseline | 115.0 mmHg | Standard Deviation 14.42 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 0.5 Hours | 5.2 mmHg | Standard Deviation 9.86 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 12 Hours | -7.8 mmHg | Standard Deviation 15.97 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 24 Hours | -7.8 mmHg | Standard Deviation 12.53 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 8 Days | -7.8 mmHg | Standard Deviation 10.87 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 3.5 Hours | -6.3 mmHg | Standard Deviation 14.83 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Baseline | 66.3 mmHg | Standard Deviation 9.1 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 0.5 Hours | 4.9 mmHg | Standard Deviation 6.83 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 1 Hour | 5.1 mmHg | Standard Deviation 6.45 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 4.5 Hours | -17.1 mmHg | Standard Deviation 11.54 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 1.5 Hours | 5.7 mmHg | Standard Deviation 7.04 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 1.5 Hours | 7.2 mmHg | Standard Deviation 12.59 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 2.5 Hours | -2.1 mmHg | Standard Deviation 6.21 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 3.5 Hours | -0.9 mmHg | Standard Deviation 12 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 2.5 Hours | -3.2 mmHg | Standard Deviation 12.26 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 1 Hour | 6.8 mmHg | Standard Deviation 21.39 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 1.5 Hours | 1.2 mmHg | Standard Deviation 16.27 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 2.5 Hours | -2.6 mmHg | Standard Deviation 18.69 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 3.5 Hours | -11.4 mmHg | Standard Deviation 10.36 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 4.5 Hours | -8.2 mmHg | Standard Deviation 2.95 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 5.5 Hours | -7.6 mmHg | Standard Deviation 2.3 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 6.5 Hours | -9.4 mmHg | Standard Deviation 15.47 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 9 Hours | -7.2 mmHg | Standard Deviation 12.38 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 12 Hours | -5.8 mmHg | Standard Deviation 19.41 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 24 Hours | -11.0 mmHg | Standard Deviation 5 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 8 Days | -5.4 mmHg | Standard Deviation 8.41 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Baseline | 71.6 mmHg | Standard Deviation 8.11 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 0.5 Hours | 1.8 mmHg | Standard Deviation 6.1 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 1 Hour | 3.6 mmHg | Standard Deviation 9.84 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 1.5 Hours | 4.0 mmHg | Standard Deviation 11.98 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Change at 0.5 Hours | 12.8 mmHg | Standard Deviation 17.54 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 3.5 Hours | -6.8 mmHg | Standard Deviation 5.54 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 4.5 Hours | -6.4 mmHg | Standard Deviation 7.54 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 5.5 Hours | -9.8 mmHg | Standard Deviation 10.03 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 6.5 Hours | -7.6 mmHg | Standard Deviation 11.01 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 9 Hours | -4.4 mmHg | Standard Deviation 10.01 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 12 Hours | -6.0 mmHg | Standard Deviation 13.06 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 24 Hours | -11.4 mmHg | Standard Deviation 10.14 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Diastolic Blood Pressure- Change at 8 Days | -7.6 mmHg | Standard Deviation 7.37 |
| Regimen 3 Placebo | Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Systolic Blood Pressure- Baseline | 112.8 mmHg | Standard Deviation 12.03 |
Primary
Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Time frame: Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose
Population: Population is Safety Analysis Set (SAF): All randomized patients who received at least one dose of study medication.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 2.5 Hours | -0.3 bpm | Standard Deviation 3.27 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Baseline | 69.0 bpm | Standard Deviation 19.3 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 6.5 Hours | 8.0 bpm | Standard Deviation 4.56 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 3.5 Hours | 1.3 bpm | Standard Deviation 7.66 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 24 Hours | 1.2 bpm | Standard Deviation 6.01 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 5.5 Hours | 4.3 bpm | Standard Deviation 5.35 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 4.5 Hours | 3.3 bpm | Standard Deviation 5.65 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 1 Hour | 3.0 bpm | Standard Deviation 7.92 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 8 Days | 0.7 bpm | Standard Deviation 10.31 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 12 Hours | 1.8 bpm | Standard Deviation 8.84 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 1.5 Hours | 2.3 bpm | Standard Deviation 8.66 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 0.5 Hours | 0.7 bpm | Standard Deviation 8.33 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 9 Hours | 4.8 bpm | Standard Deviation 10.21 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 8 Days | -7.1 bpm | Standard Deviation 20.87 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Baseline | 77.3 bpm | Standard Deviation 22.86 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 0.5 Hours | -6.0 bpm | Standard Deviation 11.88 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 1 Hour | -5.4 bpm | Standard Deviation 9.25 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 1.5 Hours | -4.0 bpm | Standard Deviation 9.73 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 2.5 Hours | -8.6 bpm | Standard Deviation 11.17 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 3.5 Hours | -1.4 bpm | Standard Deviation 14.34 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 4.5 Hours | -1.2 bpm | Standard Deviation 15.81 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 5.5 Hours | -2.9 bpm | Standard Deviation 14.14 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 6.5 Hours | -4.0 bpm | Standard Deviation 13.08 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 9 Hours | -0.9 bpm | Standard Deviation 12.32 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 12 Hours | 9.0 bpm | Standard Deviation 21.46 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 24 Hours | 2.7 bpm | Standard Deviation 17 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 8 Days | -0.8 bpm | Standard Deviation 9.18 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 6.5 Hours | 3.4 bpm | Standard Deviation 7.23 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 1.5 Hours | -3.2 bpm | Standard Deviation 8.29 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 24 Hours | 3.6 bpm | Standard Deviation 7.37 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 9 Hours | 1.8 bpm | Standard Deviation 11.48 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 1 Hour | -2.4 bpm | Standard Deviation 7.3 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Baseline | 72.0 bpm | Standard Deviation 25.52 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 12 Hours | 3.8 bpm | Standard Deviation 15.16 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 4.5 Hours | 4.0 bpm | Standard Deviation 7.35 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 3.5 Hours | 2.8 bpm | Standard Deviation 7.56 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 0.5 Hours | -2.0 bpm | Standard Deviation 8.22 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 5.5 Hours | 3.6 bpm | Standard Deviation 5.18 |
| Regimen 3 Placebo | Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change at 2.5 Hours | 0.4 bpm | Standard Deviation 9.1 |
Primary
Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Time frame: Baseline and 0.5, 1, and 1.5 hours post dose
Population: Participants Analyzed represents FAS: All randomized patients who had at least 1 dose of study drug \& who had hepatic venous pressure gradient data at baseline. (Note: 2 patients were not included in the analysis due to protocol deviations.) The number of participants included in the calculation for each timepoint is noted in the category title.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Baseline (N= 4; 9; 5) | 581.0 mL/min | Standard Deviation 77.49 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours (N= 4; 9; 5) | 53.5 mL/min | Standard Deviation 161.3 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1 Hour (N= 4; 9; 4) | 1.3 mL/min | Standard Deviation 160.23 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours (N= 4; 9; 5) | 15.8 mL/min | Standard Deviation 60.26 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours (N= 4; 9; 5) | -96.0 mL/min | Standard Deviation 390.96 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Baseline (N= 4; 9; 5) | 1182.2 mL/min | Standard Deviation 530.56 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1 Hour (N= 4; 9; 4) | -70.0 mL/min | Standard Deviation 318.35 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours (N= 4; 9; 5) | -74.1 mL/min | Standard Deviation 558.58 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours (N= 4; 9; 5) | 40.8 mL/min | Standard Deviation 154.33 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours (N= 4; 9; 5) | 73.8 mL/min | Standard Deviation 196.75 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1 Hour (N= 4; 9; 4) | -67.5 mL/min | Standard Deviation 270.27 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Baseline (N= 4; 9; 5) | 649.6 mL/min | Standard Deviation 300.44 |
Primary
Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Time frame: Baseline and 0.5, 1, and 1.5 hours post dose
Population: Participants Analyzed represents FAS: All randomized patients who had at least 1 dose of study drug \& who had hepatic venous pressure gradient data at baseline.~The number of participants included in the calculation for each timepoint is noted in the category title.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Baseline (N= 6; 9; 5) | 88.3 mmHg | Standard Deviation 11.89 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours (N= 6; 8; 5) | -6.2 mmHg | Standard Deviation 9.66 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.0 Hour (N= 6; 9; 5) | -4.2 mmHg | Standard Deviation 9.28 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours (N= 6; 9; 5) | 0 mmHg | Standard Deviation 7.77 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours (N= 6; 9; 5) | 8.8 mmHg | Standard Deviation 11.39 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Baseline (N= 6; 9; 5) | 90.3 mmHg | Standard Deviation 7.79 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.0 Hour (N= 6; 9; 5) | 5.7 mmHg | Standard Deviation 13.18 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours (N= 6; 8; 5) | 3.6 mmHg | Standard Deviation 9.97 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours (N= 6; 9; 5) | 3.4 mmHg | Standard Deviation 6.31 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours (N= 6; 8; 5) | 2.6 mmHg | Standard Deviation 4.72 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.0 Hour (N= 6; 9; 5) | 7.8 mmHg | Standard Deviation 10.92 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Baseline (N= 6; 9; 5) | 84.6 mmHg | Standard Deviation 13.63 |
Primary
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Time frame: Baseline and 0.5, 1, and 1.5 hours post dose
Population: Participants Analyzed represents Full Analysis Set (FAS): All randomized patients who had at least 1 dose of study drug \& who had hepatic venous pressure gradient data at baseline.~The number of participants per arm is consistent for all categories of the data table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Baseline | 16.58 mmHg | Standard Deviation 4.375 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours | 0.33 mmHg | Standard Deviation 1.08 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1 Hour | 0.50 mmHg | Standard Deviation 1.844 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours | 0.83 mmHg | Standard Deviation 2.113 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours | 0.83 mmHg | Standard Deviation 1.732 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Baseline | 18.33 mmHg | Standard Deviation 4.75 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1 Hour | 0.56 mmHg | Standard Deviation 1.357 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours | 0.11 mmHg | Standard Deviation 1.318 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1.5 Hours | -0.10 mmHg | Standard Deviation 1.294 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 0.5 Hours | -0.10 mmHg | Standard Deviation 0.224 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change at 1 Hour | -0.60 mmHg | Standard Deviation 0.418 |
| Regimen 3 Placebo | Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Baseline | 15.80 mmHg | Standard Deviation 6.601 |
Secondary
Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose
Baseline serum sodium value is the last measurement prior to dosing. Change from baseline is calculated as time point minus baseline.
Time frame: Baseline and 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 hours and on Day 8 post dose
Population: Participants Analyzed represents FAS: All randomized patients who had at least 1 dose of study drug \& who had hepatic venous pressure gradient data at baseline.~The number of participants included in the calculation for each timepoint is noted in the category title.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Baseline (N= 6; 9; 5) | 137.3 mEq/L | Standard Deviation 3.08 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 0.5 Hours (N= 6; 9; 5) | -1.3 mEq/L | Standard Deviation 3.01 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 1 Hour (N= 6; 9; 5) | -0.3 mEq/L | Standard Deviation 3.72 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 2.5 Hours (N= 6; 9; 5) | 1.8 mEq/L | Standard Deviation 2.56 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 4 Hours (N= 6; 9; 5) | -2.2 mEq/L | Standard Deviation 5.19 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 6.5 Hours (N= 6; 9; 5) | -1.2 mEq/L | Standard Deviation 2.32 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 9 Hours (N= 5; 9; 5) | -2.6 mEq/L | Standard Deviation 3.05 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 12 Hours (N= 6; 9; 5) | -3.7 mEq/L | Standard Deviation 2.66 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 24 Hours (N= 6; 9; 5) | -1.5 mEq/L | Standard Deviation 2.88 |
| Regimen 1 Conivaptan 12.5 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 8 Days (N= 6; 9; 5) | -2.3 mEq/L | Standard Deviation 3.2 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 24 Hours (N= 6; 9; 5) | 0.1 mEq/L | Standard Deviation 1.76 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Baseline (N= 6; 9; 5) | 137.1 mEq/L | Standard Deviation 2.8 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 6.5 Hours (N= 6; 9; 5) | 1.3 mEq/L | Standard Deviation 4.33 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 4 Hours (N= 6; 9; 5) | -1.0 mEq/L | Standard Deviation 1.87 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 0.5 Hours (N= 6; 9; 5) | -1.1 mEq/L | Standard Deviation 2.71 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 8 Days (N= 6; 9; 5) | 0.1 mEq/L | Standard Deviation 3.59 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 12 Hours (N= 6; 9; 5) | 0.1 mEq/L | Standard Deviation 3.06 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 1 Hour (N= 6; 9; 5) | 0.9 mEq/L | Standard Deviation 2.8 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 9 Hours (N= 5; 9; 5) | 0.8 mEq/L | Standard Deviation 3.46 |
| Regimen 2 Conivaptan 25 mg | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 2.5 Hours (N= 6; 9; 5) | 0.2 mEq/L | Standard Deviation 1.72 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 12 Hours (N= 6; 9; 5) | -2.2 mEq/L | Standard Deviation 2.28 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 2.5 Hours (N= 6; 9; 5) | 0.0 mEq/L | Standard Deviation 3.61 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 4 Hours (N= 6; 9; 5) | -3.6 mEq/L | Standard Deviation 1.67 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 6.5 Hours (N= 6; 9; 5) | -2.4 mEq/L | Standard Deviation 2.07 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 24 Hours (N= 6; 9; 5) | -2.0 mEq/L | Standard Deviation 3.16 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 9 Hours (N= 5; 9; 5) | -2.4 mEq/L | Standard Deviation 2.97 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Baseline (N= 6; 9; 5) | 131.2 mEq/L | Standard Deviation 6.3 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 8 Days (N= 6; 9; 5) | 2.0 mEq/L | Standard Deviation 1 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 0.5 Hours (N= 6; 9; 5) | -0.8 mEq/L | Standard Deviation 1.64 |
| Regimen 3 Placebo | Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Change at 1 Hour (N= 6; 9; 5) | -1.8 mEq/L | Standard Deviation 1.3 |