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Study of Efficacy & Safety for 3 Infusion Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia

Sponsor
Cumberland Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00478192
Collaborator
(none)
50
Enrollment
26
Locations
3
Arms
16
Duration (Months)
1.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is designed to assess the efficacy and safety of multiple infusions of conivaptan in subjects with euvolemic or hypervolemic hyponatremia

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase IIIb, Randomized, Double-Blind, Parallel Group, Multi-Center, Study to Assess the Efficacy and Safety of Multiple 30 Minute Infusions of YM087 (Conivaptan) in Subjects With Euvolemic or Hypervolemic Hyponatremia
Study Start Date :
Apr 1, 2007
Actual Primary Completion Date :
Aug 1, 2008
Actual Study Completion Date :
Aug 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Regimen 1 Conivaptan QD

20 mg conivaptan once a day

Drug: Conivaptan
premix bag
Other Names:
  • YM087
  • Vaprisol

    		•
    Experimental: Regimen 2 Conivaptan BID

    20 mg conivaptan two times a day

    Drug: Conivaptan
    premix bag
    Other Names:
  • YM087
  • Vaprisol

    		•
    Placebo Comparator: Regimen 3 Placebo

    Drug: Placebo
    premix bag

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    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

    2. 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.

    3. 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.

    4. 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.

    5. 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

    6. 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

    7. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Huntsville Alabama United States 35801
    2 Tucson Arizona United States 85723
    3 Los Angeles California United States 90073
    4 Denver Colorado United States 80218
    5 Jacksonville Florida United States 32216
    6 Port Charlotte Florida United States 33952
    7 Chicago Illinois United States 60612
    8 Indianapolis Indiana United States 46260
    9 Hazard Kentucky United States 41701
    10 Detroit Michigan United States 48201
    11 Omaha Nebraska United States 68198
    12 Bronx New York United States 10461
    13 Cincinnati Ohio United States 45267
    14 Fairfield Ohio United States 45014
    15 Toledo Ohio United States 43606
    16 Philadelphia Pennsylvania United States 19102
    17 Philadelphia Pennsylvania United States 19104
    18 Philadelphia Pennsylvania United States 19107
    19 Philadelphia Pennsylvania United States 19140
    20 Charleston South Carolina United States 29425
    21 Orangeburg South Carolina United States 29118
    22 Coimbatore India 641014
    23 Indore India 452014
    24 Jaipur India 302013
    25 Karnal India 132001
    26 Visakhapatnam India 530002

    Sponsors and Collaborators

    • Cumberland Pharmaceuticals

    Investigators

    • Study Director: Art Wheeler, MD, Cumberland Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Cumberland Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00478192
    Other Study ID Numbers:
    • 087-CL-088
    First Posted:
    May 24, 2007
    Last Update Posted:
    May 15, 2014
    Last Verified:
    Apr 1, 2014
    Keywords provided by Cumberland Pharmaceuticals
    hyponatremia
    hypervolemic
    euvolemic
    edematous
    conivaptan
    Additional relevant MeSH terms:
    Hyponatremia
    Conivaptan

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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).
    Arm/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Period Title: Overall Study
    STARTED 20 20 10
    Full Analysis Set / Safety Analysis Set 20 20 9
    End of Treatment 18 16 8
    COMPLETED 16 15 8
    NOT COMPLETED 4 5 2

    Baseline Characteristics

    Arm/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo Total
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day Total of all reporting groups
    Overall Participants 20 20 9 49
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.6
    (17.36)
    67.5
    (14.70)
    61.8
    (20.19)
    62.8
    (17.01)
    Sex: Female, Male (Count of Participants)
    Female
    7
    35%
    11
    55%
    8
    88.9%
    26
    53.1%
    Male
    13
    65%
    9
    45%
    1
    11.1%
    23
    46.9%
    Race/Ethnicity, Customized (participants) [Number]
    Asian
    7
    35%
    4
    20%
    3
    33.3%
    14
    28.6%
    Black or African American
    1
    5%
    1
    5%
    2
    22.2%
    4
    8.2%
    White
    12
    60%
    15
    75%
    4
    44.4%
    31
    63.3%

    Outcome Measures

    1. Primary Outcome
    Title Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Baseline (N= 20; 20; 9)
    126.03
    (4.017)
    126.39
    (3.581)
    125.55
    (3.648)
    Hour 48 (N=19; 17; 8)
    130.4
    (5.21)
    133.4
    (4.82)
    127.6
    (2.36)
    Change from Baseline (N=19; 17; 8)
    4.00
    (3.80)
    7.36
    (4.04)
    1.16
    (2.86)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Regimen 1 Conivaptan QD, Regimen 2 Conivaptan BID
    Comments Statistical Analysis applies to "Change from Baseline".
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments P-Values are not adjusted on the basis of multiple comparrisons
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Regimen 1 Conivaptan QD, Regimen 3 Placebo
    Comments Statistical Analysis applies to "Change from Baseline".
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.019
    Comments P-Values are not adjusted on the basis of multiple comparrisons
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Regimen 2 Conivaptan BID, Regimen 3 Placebo
    Comments Statistical Analysis applies to "Change from Baseline".
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-Values are not adjusted on the basis of multiple comparrisons
    Method ANCOVA
    Comments
    2. Secondary Outcome
    Title Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Baseline (N=20; 20; 9)
    126.03
    (4.02)
    126.39
    (3.58)
    125.55
    (3.65)
    Hour 4 (N=19; 20; 8)
    128.03
    (4.62)
    128.47
    (4.21)
    125.80
    (4.63)
    Change at Hour 4 (N=19; 20; 8)
    1.59
    (2.32)
    2.08
    (2.65)
    -0.63
    (2.77)
    Hour 12 (N=19; 19; 7)
    128.22
    (5.27)
    130.85
    (5.88)
    127.21
    (5.24)
    Change at Hour 12 (N=19; 19; 7)
    1.78
    (3.44)
    4.65
    (4.06)
    0.73
    (3.92)
    Hour 16 (N=19; 17; 7)
    129.34
    (4.51)
    131.04
    (5.07)
    127.57
    (3.78)
    Change at Hour 16 (N=19; 17; 7)
    2.90
    (3.46)
    4.93
    (3.28)
    1.09
    (2.69)
    Hour 24 (N=18; 16; 8)
    128.87
    (4.73)
    130.74
    (5.33)
    127.48
    (3.62)
    Change at Hour 24 (N=18; 16; 8)
    2.66
    (3.76)
    4.62
    (3.59)
    1.05
    (2.73)
    Hour 28 (N=19; 17; 8)
    130.79
    (4.94)
    131.62
    (4.52)
    126.49
    (4.03)
    Change at Hour 28 (N=19; 17; 8)
    4.35
    (3.80)
    5.51
    (2.75)
    0.06
    (3.30)
    Hour 36 (N=19; 15; 8)
    131.42
    (4.99)
    132.47
    (5.04)
    127.31
    (3.05)
    Change at Hour 36 (N=19; 15; 8)
    4.98
    (3.73)
    6.54
    (3.28)
    0.89
    (2.55)
    Hour 40 (N=19; 16; 8)
    130.83
    (5.04)
    132.23
    (3.99)
    127.00
    (1.85)
    Change at Hour 40 (N=19; 16; 8)
    4.39
    (3.44)
    6.30
    (3.27)
    0.58
    (1.66)
    Hour 48 (N=19; 17; 8)
    130.44
    (5.21)
    133.35
    (4.82)
    127.59
    (2.36)
    Change at Hour 48 (N=19; 17; 8)
    4.00
    (3.80)
    7.36
    (4.04)
    1.16
    (2.86)
    3. Secondary Outcome
    Title Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
    Arm/Group Title Regimen 2 Conivaptan BID
    Arm/Group Description 20 mg conivaptan two times a day
    Measure Participants 20
    Median (Inter-Quartile Range) [Hours]
    16.43
    4. Secondary Outcome
    Title Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
    Arm/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Number [Patients]
    12
    17
    2
    5. Secondary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
    Arm/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Number [Patients]
    6
    11
    0
    6. Secondary Outcome
    Title Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data.
    Arm/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Mean (Standard Deviation) [Hour * mEq/L]
    142.72
    (132.94)
    244.17
    (142.64)
    23.21
    (91.49)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Regimen 1 Conivaptan QD, Regimen 2 Conivaptan BID
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.079
    Comments
    Method ANCOVA
    Comments
    7. Secondary Outcome
    Title Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Baseline (N=16; 12; 6)
    6.76
    (47.91)
    39.86
    (245.23)
    18.66
    (45.05)
    Hour 12 (N=14; 12; 5)
    355.65
    (684.35)
    405.21
    (744.88)
    136.22
    (154.94)
    Change at Hour 12 (N=12;12; 4)
    301.52
    (671.78)
    365.35
    (699.96)
    135.44
    (123.36)
    Hour 24 (N=14; 12; 6)
    -50.19
    (794.22)
    -261.27
    (1009.24)
    368.01
    (688.81)
    Change at Hour 24 (N=13; 11; 5)
    -70.61
    (796.01)
    -391.76
    (1206.39)
    383.73
    (723.33)
    Hour 36 (N=15; 11; 6)
    36.85
    (905.18)
    12.66
    (743.24)
    726.96
    (1013.78)
    Change at Hour 36 (N=12; 8; 5)
    -91.07
    (912.66)
    -89.12
    (805.36)
    810.45
    (1079.89)
    Hour 48 (N=14; 11; 5)
    -77.37
    (1169.30)
    -179.37
    (852.58)
    569.09
    (1392.07)
    Change at Hour 48 (N=12; 10; 4)
    80.23
    (1116.99)
    -240.39
    (759.82)
    690.98
    (2872.2)
    8. Secondary Outcome
    Title Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    Measure Participants 20 20 9
    Baseline (N=14; 11; 6)
    -53.87
    (45.47)
    6.55
    (165.07)
    -34.90
    (74.32)
    Hour 24 (N=14; 12; 6)
    -972.29
    (1455.66)
    -611.14
    (693.863)
    -416.71
    (666.97)
    Change at Hour 24 (N=11; 10; 5)
    -936.99
    (1618.46)
    -513.33
    (566.72)
    -420.75
    (747.84)
    Hour 48 (N=14;12; 5)
    -1243.39
    (2211.22)
    -769.19
    (934.31)
    -592.96
    (1050.94)
    Change at Hour 48 (N=11; 10; 4)
    -1313.98
    (2477.39)
    -603.67
    (761.90)
    -702.11
    (1117.92)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description An Adverse Event was defined as treatment emergent if it occurred after the first dose of study drug through the ninth day after the last dose. Participants at Risk represent the Safety Analysis Set.
    Arm/Group Title Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Arm/Group Description 20 mg conivaptan once a day 20 mg conivaptan two times a day
    All Cause Mortality
    Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/20 (30%) 5/20 (25%) 2/9 (22.2%)
    Blood and lymphatic system disorders
    Coagulopathy 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Cardiac disorders
    Cardiac failure congestive 2/20 (10%) 1/20 (5%) 0/9 (0%)
    Gastrointestinal disorders
    Ileus 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    General disorders
    Multi-organ failure 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Infections and infestations
    Clostridium difficile colitis 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Pneumonia 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Metabolism and nutrition disorders
    Hyperkalaemia 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Hyponatraemia 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Nervous system disorders
    Transient ischaemic attack 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Psychiatric disorders
    Delirium 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Renal and urinary disorders
    Renal failure 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Renal failure acute 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory acidosis 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Respiratory distress 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Surgical and medical procedures
    Coronary artery bypass 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Vascular disorders
    Hypotension 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Other (Not Including Serious) Adverse Events
    Regimen 1 Conivaptan QD Regimen 2 Conivaptan BID Regimen 3 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/20 (35%) 10/20 (50%) 5/9 (55.6%)
    Blood and lymphatic system disorders
    Anaemia 2/20 (10%) 1/20 (5%) 1/9 (11.1%)
    Hypocoagulable state 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Leukocytosis 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Cardiac disorders
    Supraventricular tachycardia 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Ventricular arrthmia 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Endocrine disorders
    Hypothyrodism 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Eye disorders
    Dry eye 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Abdominal distention 2/20 (10%) 0/20 (0%) 0/9 (0%)
    Abdominal pain 1/20 (5%) 0/20 (0%) 1/9 (11.1%)
    Bowel sounds abnormal 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Constipation 2/20 (10%) 2/20 (10%) 0/9 (0%)
    Gastric haemorrhage 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Nausea 2/20 (10%) 1/20 (5%) 0/9 (0%)
    Vomiting 0/20 (0%) 2/20 (10%) 0/9 (0%)
    General disorders
    Chest pain 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Fatigue 1/20 (5%) 1/20 (5%) 0/9 (0%)
    Hypothermia 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Oedema peripheral 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Pain 2/20 (10%) 0/20 (0%) 0/9 (0%)
    Infections and infestations
    Bronchitis chronic 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Urinary tract infection 0/20 (0%) 2/20 (10%) 1/9 (11.1%)
    Injury, poisoning and procedural complications
    Contusion 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Fall 0/20 (0%) 0/20 (0%) 2/9 (22.2%)
    Procedural pain 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Investigations
    Blood creatine phosphokinaise increased 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Blood presure decreased 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Breath sounds abnormal 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Cardiac murmur 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Carotid bruit 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Chest X-ray abnormal 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Heart sounds abnormal 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Hyperglycaemia 1/20 (5%) 0/20 (0%) 1/9 (11.1%)
    Hypernatraemia 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Hypervolaemia 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Hypoalbuminaemia 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Hypokalaemia 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Hypomagnesaemia 2/20 (10%) 0/20 (0%) 0/9 (0%)
    Hypophosphataemia 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Hypovolaemia 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Musculoskeletal and connective tissue disorders
    Muscle spasms 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Neck pain 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Nervous system disorders
    Dizziness 0/20 (0%) 1/20 (5%) 1/9 (11.1%)
    Headache 1/20 (5%) 1/20 (5%) 0/9 (0%)
    Lethargy 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Psychiatric disorders
    Anxiety 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Insomnia 0/20 (0%) 2/20 (10%) 0/9 (0%)
    Psychotic disorder 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Restlessness 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Renal and urinary disorders
    Dysuria 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Haematuria 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Postnasal drip 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Rales 1/20 (5%) 0/20 (0%) 0/9 (0%)
    Rhinitis allergic 0/20 (0%) 0/20 (0%) 1/9 (11.1%)
    Skin and subcutaneous tissue disorders
    Pruritus 1/20 (5%) 1/20 (5%) 0/9 (0%)
    Vascular disorders
    Haematoma 0/20 (0%) 1/20 (5%) 0/9 (0%)
    Hypotension 3/20 (15%) 0/20 (0%) 1/9 (11.1%)
    Thrombophlebitis 0/20 (0%) 1/20 (5%) 0/9 (0%)

    Limitations/Caveats

    Company makes no warranties or representations of any kind as to the currency or completeness of the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose and shall not be liable for any damages.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 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.

    Results Point of Contact

    Name/Title Senior Medical Director, Medical Affairs
    Organization Astellas Pharma Global Development
    Phone
    Email clinicaltrials@us.astellas.com
    Responsible Party:
    Cumberland Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00478192
    Other Study ID Numbers:
    • 087-CL-088
    First Posted:
    May 24, 2007
    Last Update Posted:
    May 15, 2014
    Last Verified:
    Apr 1, 2014