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A Study of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia

Sponsor
Cumberland Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00435591
Collaborator
(none)
121
Enrollment
18
Locations
4
Arms
20
Duration (Months)
6.7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will evaluate the effectiveness and safety of multiple dosing regimens of IV conivaptan in subjects with euvolemic or hypervolemic hyponatremia

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
121 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 4, Randomized, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia
Study Start Date :
Jan 1, 2007
Actual Primary Completion Date :
Sep 1, 2008
Actual Study Completion Date :
Sep 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Regimen 1

Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule

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

    • Drug: placebo
    ampoule or premix bag
    Experimental: Dose Regimen 2

    Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule

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

    		•
    Experimental: Dose Regimen 3

    Placebo loading dose + 20mg/day continuous infusion conivaptan per premix bag

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

    • Drug: placebo
    ampoule or premix bag
    Experimental: Dose Regimen 4

    Conivaptan loading dose (20mg) + 20mg/day continuous infusion conivaptan per premix bag

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 [48 hours]

      Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion. One ISRMS has been reported for each participant & represents the most severe state of ISR for that participant. ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis

    Secondary Outcome Measures

    1. Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period [Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment]

      Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. Change from Baseline is calculated as Time point minus Baseline.

    2. Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours [24.5 hours, 48.5 hours and 96.5 hours]

      AUCna t is calculated as the baseline-adjusted area under serum sodium levels for a duration of time 0 to time t. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.

    3. Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period [48.5 hours]

      The upper limits of the interquartile range were not estimable in three of the treatment arms. Only the "placebo loading dose + YM087 premix continuous infusion" arm will be reported. Time is number of hours to reach an increase of exceeding 4 mEq/L from baseline serum sodium. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.

    4. Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours [0-24.5 hours, 0-48.5 hours and 0-96.5 hours]

      Patients with confirmed serum sodium level exceeding 4 mEq/L increase from baseline. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.

    5. Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours [0-24.5 hours, 0-48.5 hours and 0-96.5 hours]

      Patients with confirmed serum sodium level exceeding 6 mEq/L increase from baseline or confirmed normal serum sodium level exceeding 135 mEq/L. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Subject has a serum sodium value between 115 and 133 mEq/L

    • Subject is euvolemic or hypervolemic

    Exclusion Criteria:

    • Clinical evidence of volume depletion or dehydration

    • Uncontrolled brady- or tachyarrhythmias requiring emergent pacemaker placement or treatment

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Charleston South Carolina United States 29425
    2 Bangalore India 560034
    3 Bangalore India 560099
    4 Bhopal India 462001
    5 Hyderabaad India 500482
    6 Karnal India 132001
    7 Afula Israel 18101
    8 Ashkelon Israel 78308
    9 Haifa Israel 31048
    10 Haifa Israel 34362
    11 Holon Israel 58100
    12 Jerusalem Israel 910301
    13 Jerusalem Israel 91120
    14 Rechovot Israel 76100
    15 Safed Israel 13100
    16 Tel Hashomer Israel 52621
    17 Tel-Aviv Israel 64239
    18 Zerifin Israel 70300

    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:
    NCT00435591
    Other Study ID Numbers:
    • 087-CL-084
    First Posted:
    Feb 15, 2007
    Last Update Posted:
    May 15, 2014
    Last Verified:
    Apr 1, 2014
    Keywords provided by Cumberland Pharmaceuticals
    Hyponatremia
    Euvolemia
    Hypervolemia
    Conivaptan
    Vaprisol®
    YM087
    Additional relevant MeSH terms:
    Hyponatremia
    Conivaptan

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag
    Period Title: Overall Study
    STARTED 30 31 30 30
    Safety Analysis Set 28 30 30 29
    Full Analysis Set 28 29 30 29
    End of Treatment 25 27 27 23
    COMPLETED 23 27 25 19
    NOT COMPLETED 7 4 5 11

    Baseline Characteristics

    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4 Total
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag Total of all reporting groups
    Overall Participants 28 30 30 29 117
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.1
    (20.28)
    61.1
    (20.14)
    64.8
    (14.13)
    63.3
    (22.31)
    62.1
    (19.28)
    Sex: Female, Male (Count of Participants)
    Female
    14
    50%
    13
    43.3%
    16
    53.3%
    18
    62.1%
    61
    52.1%
    Male
    14
    50%
    17
    56.7%
    14
    46.7%
    11
    37.9%
    56
    47.9%
    Race/Ethnicity, Customized (Number) [Number]
    White
    14
    50%
    16
    53.3%
    14
    46.7%
    16
    55.2%
    60
    51.3%
    Black/ African -American
    0
    0%
    1
    3.3%
    0
    0%
    0
    0%
    1
    0.9%
    Asian
    14
    50%
    13
    43.3%
    15
    50%
    13
    44.8%
    55
    47%
    American Indian / Alaskan
    0
    0%
    0
    0%
    1
    3.3%
    0
    0%
    1
    0.9%
    Volume Status/ Underlying Cause of Hyponatremia (Number) [Number]
    Euvolemic/ SIADH
    15
    53.6%
    11
    36.7%
    11
    36.7%
    9
    31%
    46
    39.3%
    Euvolemic/ CHF
    1
    3.6%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    Euvolemic/ Malignancy
    0
    0%
    1
    3.3%
    3
    10%
    0
    0%
    4
    3.4%
    Euvolemic/ Idiopathic
    0
    0%
    1
    3.3%
    1
    3.3%
    2
    6.9%
    4
    3.4%
    Euvolemic/ COPD
    1
    3.6%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    Euvolemic/ Unknown
    6
    21.4%
    8
    26.7%
    8
    26.7%
    10
    34.5%
    32
    27.4%
    Euvolemic/ Other
    2
    7.1%
    7
    23.3%
    4
    13.3%
    6
    20.7%
    19
    16.2%
    Hypervolemic/ SIADH
    0
    0%
    0
    0%
    1
    3.3%
    0
    0%
    1
    0.9%
    Hypervolemic/ CHF
    3
    10.7%
    2
    6.7%
    0
    0%
    2
    6.9%
    7
    6%
    Hypervolemic/ Unknown
    0
    0%
    0
    0%
    2
    6.7%
    0
    0%
    2
    1.7%

    Outcome Measures

    1. Primary Outcome
    Title Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2
    Description Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion. One ISRMS has been reported for each participant & represents the most severe state of ISR for that participant. ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis
    Time Frame 48 hours

    Outcome Measure Data

    Analysis Population Description
    Population is Safety Analysis Set (SAF): All randomized patients who received at least 1 dose of study drug. The number of participants per arm is consistent for all categories of the data table.
    Arm/Group Title Dose Regimen 1 Dose Regimen 2
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule
    Measure Participants 28 30
    Infusion Site Reaction - No assessment
    0
    0%
    1
    3.3%
    Infusion Site Reaction - 0
    17
    60.7%
    16
    53.3%
    Infusion Site Reaction - 1+
    5
    17.9%
    7
    23.3%
    Infusion Site Reaction - 2+
    2
    7.1%
    0
    0%
    Infusion Site Reaction - 3+
    4
    14.3%
    5
    16.7%
    Infusion Site Reaction - 4+
    0
    0%
    1
    3.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Dose Regimen 1, Dose Regimen 2
    Comments Aggregated data were used to determine differences between groups. Statistical analysis is relevant to the aggregated data of all rows except the "no assessment" row.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 0.23
    Confidence Interval (2-Sided) 95%
    -0.37 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period
    Description Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period. Change from Baseline is calculated as Time point minus Baseline.
    Time Frame Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment

    Outcome Measure Data

    Analysis Population Description
    Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data. The number of participants analyzed per arm represents Full Analysis Set. The numbers of participants for each time point are noted in the category titles.
    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag
    Measure Participants 28 29 30 29
    Baseline
    124.6
    (3.75)
    123.5
    (4.08)
    124.5
    (3.67)
    124.0
    (4.63)
    Change at Hour 4 (N=28; 26; 30; 28)
    1.2
    (3.67)
    1.5
    (2.67)
    0.7
    (2.13)
    1.9
    (3.92)
    Change at Hour 6 (N=27; 27; 29; 27)
    1.1
    (1.96)
    2.5
    (2.88)
    1.5
    (2.70)
    2.7
    (3.23)
    Change at Hour 10 (N=27; 28; 30; 26)
    2.3
    (2.92)
    2.9
    (3.09)
    2.7
    (3.88)
    2.9
    (3.40)
    Change at Hour 16 (N=24; 24; 27; 23)
    2.0
    (2.93)
    4.0
    (4.09)
    4.2
    (3.82)
    4.8
    (3.90)
    Change at Hour 24 (N= 27; 27; 30; 24)
    3.3
    (3.23)
    4.5
    (3.85)
    4.4
    (4.43)
    5.0
    (3.81)
    Change at Hour 30 (N=27; 28; 28; 23)
    3.1
    (4.13)
    4.5
    (3.51)
    4.8
    (4.14)
    4.1
    (2.81)
    Change at Hour 40 (N=24; 26; 26; 24)
    4.3
    (3.01)
    5.1
    (4.14)
    6.9
    (4.68)
    6.1
    (4.52)
    Change at Hour 48.5 (N=26; 28; 28; 27)
    4.6
    (4.01)
    5.8
    (4.63)
    6.5
    (4.19)
    5.4
    (4.37)
    Change at Day 7 (N=23; 27; 25; 17)
    6.7
    (5.87)
    9.6
    (5.17)
    7.2
    (4.22)
    8.9
    (5.11)
    3. Secondary Outcome
    Title Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours
    Description AUCna t is calculated as the baseline-adjusted area under serum sodium levels for a duration of time 0 to time t. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
    Time Frame 24.5 hours, 48.5 hours and 96.5 hours

    Outcome Measure Data

    Analysis Population Description
    Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data. The number of participants per arm is consistent for all categories of the data table.
    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag
    Measure Participants 28 29 30 29
    AUCna at 24.5 hours
    45.600
    (55.919)
    70.569
    (73.042)
    66.096
    (73.662)
    82.470
    (82.195)
    AUCna at 48.5 hours
    133.664
    (127.156)
    194.561
    (166.015)
    205.522
    (163.261)
    207.043
    (170.153)
    AUCna at 96.5 hours
    375.379
    (331.298)
    503.127
    (340.247)
    558.926
    (351.718)
    528.377
    (371.075)
    4. Secondary Outcome
    Title Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period
    Description The upper limits of the interquartile range were not estimable in three of the treatment arms. Only the "placebo loading dose + YM087 premix continuous infusion" arm will be reported. Time is number of hours to reach an increase of exceeding 4 mEq/L from baseline serum sodium. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
    Time Frame 48.5 hours

    Outcome Measure Data

    Analysis Population Description
    Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data. The number of participants per arm is consistent for all categories of the data table.
    Arm/Group Title Dose Regimen 3
    Arm/Group Description Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag
    Measure Participants 30
    Median (Inter-Quartile Range) [Hours]
    24.08
    5. Secondary Outcome
    Title Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
    Description Patients with confirmed serum sodium level exceeding 4 mEq/L increase from baseline. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
    Time Frame 0-24.5 hours, 0-48.5 hours and 0-96.5 hours

    Outcome Measure Data

    Analysis Population Description
    Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data. The number of participants per arm is consistent for all categories of the data table.
    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20mg)+20mg/day continuous infusion conivaptan per premix bag
    Measure Participants 28 29 30 29
    0 - 24.5 Hours
    6
    21.4%
    13
    43.3%
    13
    43.3%
    10
    34.5%
    0 - 48.5 Hours
    13
    46.4%
    15
    50%
    23
    76.7%
    19
    65.5%
    0 - 96.5 Hours
    21
    75%
    22
    73.3%
    27
    90%
    24
    82.8%
    6. Secondary Outcome
    Title Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
    Description Patients with confirmed serum sodium level exceeding 6 mEq/L increase from baseline or confirmed normal serum sodium level exceeding 135 mEq/L. Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
    Time Frame 0-24.5 hours, 0-48.5 hours and 0-96.5 hours

    Outcome Measure Data

    Analysis Population Description
    Population is Full Analysis Set (FAS): All randomized patients who received at least 1 dose of study drug and who had both baseline and postbaseline serum sodium data. The number of participants per arm is consistent for all categories of the data table.
    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag
    Measure Participants 28 29 30 29
    0 - 24.5 Hours
    1
    3.6%
    6
    20%
    7
    23.3%
    6
    20.7%
    0 - 48.5 Hours
    6
    21.4%
    13
    43.3%
    17
    56.7%
    12
    41.4%
    0 - 96.5 Hours
    13
    46.4%
    16
    53.3%
    24
    80%
    19
    65.5%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Numbers of Participants at Risk represent the Safety Analysis Set (SAF). AE collection began at the start of study drug infusion and continued through Post Treatment Period Day 7. AEs collected in this time interval were defined as treatment emergent AEs (TEAEs) for patients who completed or prematurely discontinued study drug.
    Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Arm/Group Description Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag Conivaptan loading dose (20 mg) + 20 mg/day continuous infusion conivaptan per premix bag
    All Cause Mortality
    Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/28 (7.1%) 5/30 (16.7%) 8/30 (26.7%) 2/29 (6.9%)
    Cardiac disorders
    Cardiac failure congestive 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Gastrointestinal disorders
    Diarrhoea 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Intestinal obstruction 0/28 (0%) 0/30 (0%) 0/30 (0%) 1/29 (3.4%)
    Hepatobiliary disorders
    Bile duct obstruction 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Infections and infestations
    Bacteraemia 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Cellulitis 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Pneumonia 0/28 (0%) 1/30 (3.3%) 0/30 (0%) 0/29 (0%)
    Urinary tract infection 1/28 (3.6%) 1/30 (3.3%) 0/30 (0%) 0/29 (0%)
    Injury, poisoning and procedural complications
    Collapse of lung 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 0/28 (0%) 0/30 (0%) 0/30 (0%) 1/29 (3.4%)
    Bladder cancer 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Neoplasm malignant 0/28 (0%) 1/30 (3.3%) 0/30 (0%) 0/29 (0%)
    Ovarian cancer metastatic 0/28 (0%) 1/30 (3.3%) 0/30 (0%) 0/29 (0%)
    Renal and urinary disorders
    Renal failure 0/28 (0%) 1/30 (3.3%) 1/30 (3.3%) 0/29 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 0/28 (0%) 1/30 (3.3%) 0/30 (0%) 0/29 (0%)
    Pulmonary congestion 0/28 (0%) 1/30 (3.3%) 0/30 (0%) 0/29 (0%)
    Pulmonary embolism 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Respiratory distress 1/28 (3.6%) 0/30 (0%) 0/30 (0%) 0/29 (0%)
    Surgical and medical procedures
    Haemodialysis 0/28 (0%) 0/30 (0%) 1/30 (3.3%) 0/29 (0%)
    Other (Not Including Serious) Adverse Events
    Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/28 (21.4%) 12/30 (40%) 4/30 (13.3%) 8/29 (27.6%)
    Blood and lymphatic system disorders
    Anaemia 0/28 (0%) 4/30 (13.3%) 0/30 (0%) 0/29 (0%)
    Gastrointestinal disorders
    Constipation 3/28 (10.7%) 5/30 (16.7%) 2/30 (6.7%) 0/29 (0%)
    Diarrhoea 0/28 (0%) 6/30 (20%) 0/30 (0%) 4/29 (13.8%)
    General disorders
    Chest pain 2/28 (7.1%) 0/30 (0%) 2/30 (6.7%) 0/29 (0%)
    Pyrexia 0/28 (0%) 0/30 (0%) 0/30 (0%) 2/29 (6.9%)
    Metabolism and nutrition disorders
    Hyperkalaemia 0/28 (0%) 2/30 (6.7%) 0/30 (0%) 0/29 (0%)
    Hypokalaemia 0/28 (0%) 0/30 (0%) 0/30 (0%) 4/29 (13.8%)
    Nervous system disorders
    Headache 3/28 (10.7%) 0/30 (0%) 0/30 (0%) 0/29 (0%)
    Somnolence 0/28 (0%) 2/30 (6.7%) 0/30 (0%) 0/29 (0%)
    Vascular disorders
    Hypotension 0/28 (0%) 0/30 (0%) 0/30 (0%) 2/29 (6.9%)

    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 Medial Director, Medical Affairs
    Organization Astellas Pharma Global Development
    Phone
    Email clinicaltrials@us.astellas.com
    Responsible Party:
    Cumberland Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00435591
    Other Study ID Numbers:
    • 087-CL-084
    First Posted:
    Feb 15, 2007
    Last Update Posted:
    May 15, 2014
    Last Verified:
    Apr 1, 2014