Trial Outcomes & Findings for A Study to Assess the Safety and Effects of Intravenous (IV) Conivaptan on the Hepatic Hemodynamic Response in Cirrhotic Patients (NCT NCT00592475)
NCT ID: NCT00592475
Last Updated: 2014-05-15
Results Overview
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Baseline and 0.5, 1, and 1.5 hours post dose
Results posted on
2014-05-15
Participant Flow
Participant milestones
| Measure |
Regimen 1 Conivaptan 12.5 mg
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
9
|
5
|
|
Overall Study
COMPLETED
|
6
|
9
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess the Safety and Effects of Intravenous (IV) Conivaptan on the Hepatic Hemodynamic Response in Cirrhotic Patients
Baseline characteristics by cohort
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63.7 years
STANDARD_DEVIATION 8.52 • n=93 Participants
|
60.0 years
STANDARD_DEVIATION 9.72 • n=4 Participants
|
55.2 years
STANDARD_DEVIATION 7.19 • n=27 Participants
|
59.9 years
STANDARD_DEVIATION 8.95 • n=483 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
15 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
6 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
20 Participants
n=483 Participants
|
|
Underlying Cause of Hyponatremia
Euvolemic - Cirrhosis
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Underlying Cause of Hyponatremia
Euvolemic - Not Hyponatremia
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Underlying Cause of Hyponatremia
Euvolemic - Other
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Underlying Cause of Hyponatremia
Hypervolemic - Cirrhosis
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Underlying Cause of Hyponatremia
Hypervolemic - Not Hyponatremia
|
0 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Underlying Cause of Hyponatremia
Hypervolemic - Other
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline and 0.5, 1, and 1.5 hours post dosePopulation: 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.
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Outcome measures
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
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
|
18.33 mmHg
Standard Deviation 4.750
|
15.80 mmHg
Standard Deviation 6.601
|
|
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 1.080
|
0.11 mmHg
Standard Deviation 1.318
|
-0.10 mmHg
Standard Deviation 0.224
|
|
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
|
0.56 mmHg
Standard Deviation 1.357
|
-0.60 mmHg
Standard Deviation 0.418
|
|
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
|
0.83 mmHg
Standard Deviation 1.732
|
-0.10 mmHg
Standard Deviation 1.294
|
PRIMARY outcome
Timeframe: Baseline and 0.5, 1, and 1.5 hours post dosePopulation: 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.
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Outcome measures
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
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
|
1182.2 mL/min
Standard Deviation 530.56
|
649.6 mL/min
Standard Deviation 300.44
|
|
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 161.30
|
-74.1 mL/min
Standard Deviation 558.58
|
73.8 mL/min
Standard Deviation 196.75
|
|
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
|
-70.0 mL/min
Standard Deviation 318.35
|
-67.5 mL/min
Standard Deviation 270.27
|
|
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
|
-96.0 mL/min
Standard Deviation 390.96
|
40.8 mL/min
Standard Deviation 154.33
|
PRIMARY outcome
Timeframe: Baseline and 0.5, 1, and 1.5 hours post dosePopulation: 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.
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Outcome measures
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
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
|
5.7 mmHg
Standard Deviation 13.18
|
7.8 mmHg
Standard Deviation 10.92
|
|
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
|
90.3 mmHg
Standard Deviation 7.79
|
84.6 mmHg
Standard Deviation 13.63
|
|
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
|
3.6 mmHg
Standard Deviation 9.97
|
2.6 mmHg
Standard Deviation 4.72
|
|
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
|
8.8 mmHg
Standard Deviation 11.39
|
3.4 mmHg
Standard Deviation 6.31
|
PRIMARY outcome
Timeframe: 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 dosePopulation: 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.
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Outcome measures
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
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
|
115.0 mmHg
Standard Deviation 14.42
|
112.8 mmHg
Standard Deviation 12.03
|
|
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
|
5.2 mmHg
Standard Deviation 9.86
|
12.8 mmHg
Standard Deviation 17.54
|
|
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
|
13.9 mmHg
Standard Deviation 14.12
|
6.8 mmHg
Standard Deviation 21.39
|
|
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 20.90
|
7.2 mmHg
Standard Deviation 12.59
|
1.2 mmHg
Standard Deviation 16.27
|
|
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
|
-3.8 mmHg
Standard Deviation 8.15
|
-2.6 mmHg
Standard Deviation 18.69
|
|
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
|
-6.3 mmHg
Standard Deviation 14.83
|
-11.4 mmHg
Standard Deviation 10.36
|
|
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
|
-17.1 mmHg
Standard Deviation 11.54
|
-8.2 mmHg
Standard Deviation 2.95
|
|
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 7.20
|
-8.7 mmHg
Standard Deviation 14.94
|
-7.6 mmHg
Standard Deviation 2.30
|
|
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
|
-9.7 mmHg
Standard Deviation 7.73
|
-9.4 mmHg
Standard Deviation 15.47
|
|
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
|
1.9 mmHg
Standard Deviation 11.46
|
-7.2 mmHg
Standard Deviation 12.38
|
|
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
|
-7.8 mmHg
Standard Deviation 15.97
|
-5.8 mmHg
Standard Deviation 19.41
|
|
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
|
-7.8 mmHg
Standard Deviation 12.53
|
-11.0 mmHg
Standard Deviation 5.00
|
|
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
|
-7.8 mmHg
Standard Deviation 10.87
|
-5.4 mmHg
Standard Deviation 8.41
|
|
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
|
66.3 mmHg
Standard Deviation 9.10
|
71.6 mmHg
Standard Deviation 8.11
|
|
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
|
4.9 mmHg
Standard Deviation 6.83
|
1.8 mmHg
Standard Deviation 6.10
|
|
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
|
5.1 mmHg
Standard Deviation 6.45
|
3.6 mmHg
Standard Deviation 9.84
|
|
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
|
5.7 mmHg
Standard Deviation 7.04
|
4.0 mmHg
Standard Deviation 11.98
|
|
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
|
-2.1 mmHg
Standard Deviation 6.21
|
-3.2 mmHg
Standard Deviation 12.26
|
|
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
|
-0.9 mmHg
Standard Deviation 12.00
|
-6.8 mmHg
Standard Deviation 5.54
|
|
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
|
-6.3 mmHg
Standard Deviation 7.45
|
-6.4 mmHg
Standard Deviation 7.54
|
|
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
|
-4.2 mmHg
Standard Deviation 7.79
|
-9.8 mmHg
Standard Deviation 10.03
|
|
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
|
-4.7 mmHg
Standard Deviation 6.20
|
-7.6 mmHg
Standard Deviation 11.01
|
|
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
|
0.3 mmHg
Standard Deviation 4.82
|
-4.4 mmHg
Standard Deviation 10.01
|
|
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
|
-3.3 mmHg
Standard Deviation 6.42
|
-6.0 mmHg
Standard Deviation 13.06
|
|
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
|
-5.1 mmHg
Standard Deviation 5.56
|
-11.4 mmHg
Standard Deviation 10.14
|
|
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
|
-5.0 mmHg
Standard Deviation 9.55
|
-7.6 mmHg
Standard Deviation 7.37
|
PRIMARY outcome
Timeframe: 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 dosePopulation: 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.
Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration.
Outcome measures
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
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 19.30
|
77.3 bpm
Standard Deviation 22.86
|
72.0 bpm
Standard Deviation 25.52
|
|
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
|
-6.0 bpm
Standard Deviation 11.88
|
-2.0 bpm
Standard Deviation 8.22
|
|
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
|
-5.4 bpm
Standard Deviation 9.25
|
-2.4 bpm
Standard Deviation 7.30
|
|
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
|
-4.0 bpm
Standard Deviation 9.73
|
-3.2 bpm
Standard Deviation 8.29
|
|
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
|
-8.6 bpm
Standard Deviation 11.17
|
0.4 bpm
Standard Deviation 9.10
|
|
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
|
-1.4 bpm
Standard Deviation 14.34
|
2.8 bpm
Standard Deviation 7.56
|
|
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
|
-1.2 bpm
Standard Deviation 15.81
|
4.0 bpm
Standard Deviation 7.35
|
|
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
|
-2.9 bpm
Standard Deviation 14.14
|
3.6 bpm
Standard Deviation 5.18
|
|
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
|
-4.0 bpm
Standard Deviation 13.08
|
3.4 bpm
Standard Deviation 7.23
|
|
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
|
-0.9 bpm
Standard Deviation 12.32
|
1.8 bpm
Standard Deviation 11.48
|
|
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
|
9.0 bpm
Standard Deviation 21.46
|
3.8 bpm
Standard Deviation 15.16
|
|
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
|
2.7 bpm
Standard Deviation 17.00
|
3.6 bpm
Standard Deviation 7.37
|
|
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
|
-7.1 bpm
Standard Deviation 20.87
|
-0.8 bpm
Standard Deviation 9.18
|
SECONDARY outcome
Timeframe: Baseline and 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 hours and on Day 8 post dosePopulation: 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.
Baseline serum sodium value is the last measurement prior to dosing. Change from baseline is calculated as time point minus baseline.
Outcome measures
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 Participants
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 Participants
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 Participants
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
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
|
137.1 mEq/L
Standard Deviation 2.80
|
131.2 mEq/L
Standard Deviation 6.30
|
|
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
|
-1.1 mEq/L
Standard Deviation 2.71
|
-0.8 mEq/L
Standard Deviation 1.64
|
|
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
|
0.9 mEq/L
Standard Deviation 2.80
|
-1.8 mEq/L
Standard Deviation 1.30
|
|
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
|
0.2 mEq/L
Standard Deviation 1.72
|
0.0 mEq/L
Standard Deviation 3.61
|
|
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
|
-1.0 mEq/L
Standard Deviation 1.87
|
-3.6 mEq/L
Standard Deviation 1.67
|
|
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
|
1.3 mEq/L
Standard Deviation 4.33
|
-2.4 mEq/L
Standard Deviation 2.07
|
|
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
|
0.8 mEq/L
Standard Deviation 3.46
|
-2.4 mEq/L
Standard Deviation 2.97
|
|
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
|
0.1 mEq/L
Standard Deviation 3.06
|
-2.2 mEq/L
Standard Deviation 2.28
|
|
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
|
0.1 mEq/L
Standard Deviation 1.76
|
-2.0 mEq/L
Standard Deviation 3.16
|
|
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 3.20
|
0.1 mEq/L
Standard Deviation 3.59
|
2.0 mEq/L
Standard Deviation 1.00
|
Adverse Events
Regimen 1 Conivaptan 12.5 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Regimen 2 Conivaptan 25 mg
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Regimen 3 Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 participants at risk
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 participants at risk
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 participants at risk
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
Cardiac disorders
Atrial tachycardia
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
Other adverse events
| Measure |
Regimen 1 Conivaptan 12.5 mg
n=6 participants at risk
Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours
|
Regimen 2 Conivaptan 25 mg
n=9 participants at risk
Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours
|
Regimen 3 Placebo
n=5 participants at risk
Placebo continuous intravenous infusion over 6.5 hours
|
|---|---|---|---|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Metabolism and nutrition disorders
Polydipsia
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
11.1%
1/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
|
Vascular disorders
Phlebitis
|
0.00%
0/6
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
22.2%
2/9
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
0.00%
0/5
Treatment-Emergent Adverse Event (TEAE) is an event that occurred after the first dose of study drug through 24 hours after the last dose of study drug.
|
Additional Information
Senior Medical Director, Medical Affairs
Astellas Pharma Global Development
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated from the Study. Sponsor must receive the manuscript 60 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.
- Publication restrictions are in place
Restriction type: OTHER