We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00435591
Recruitment Status : Completed
First Posted : February 15, 2007
Results First Posted : May 26, 2010
Last Update Posted : May 15, 2014
Sponsor:
Information provided by (Responsible Party):
Cumberland Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Hyponatremia
Euvolemia
Hypervolemia
Interventions Drug: Conivaptan
Drug: placebo
Enrollment 121
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
Hide 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
Arm/Group Title Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4 Total
Hide 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 Number of Baseline Participants 28 30 30 29 117
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants 30 participants 30 participants 29 participants 117 participants
59.1  (20.28) 61.1  (20.14) 64.8  (14.13) 63.3  (22.31) 62.1  (19.28)
[1]
Measure Description: Population represented is Safety Analysis Set (SAF)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 30 participants 30 participants 29 participants 117 participants
Female
14
  50.0%
13
  43.3%
16
  53.3%
18
  62.1%
61
  52.1%
Male
14
  50.0%
17
  56.7%
14
  46.7%
11
  37.9%
56
  47.9%
[1]
Measure Description: Population represented is Safety Analysis Set (SAF)
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants 30 participants 30 participants 29 participants 117 participants
White 14 16 14 16 60
Black/ African -American 0 1 0 0 1
Asian 14 13 15 13 55
American Indian / Alaskan 0 0 1 0 1
[1]
Measure Description: Population represented is Safety Analysis Set (SAF)
Volume Status/ Underlying Cause of Hyponatremia   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants 30 participants 30 participants 29 participants 117 participants
Euvolemic/ SIADH 15 11 11 9 46
Euvolemic/ CHF 1 0 0 0 1
Euvolemic/ Malignancy 0 1 3 0 4
Euvolemic/ Idiopathic 0 1 1 2 4
Euvolemic/ COPD 1 0 0 0 1
Euvolemic/ Unknown 6 8 8 10 32
Euvolemic/ Other 2 7 4 6 19
Hypervolemic/ SIADH 0 0 1 0 1
Hypervolemic/ CHF 3 2 0 2 7
Hypervolemic/ Unknown 0 0 2 0 2
[1]
Measure Description:

Population represented is Safety Analysis Set (SAF)

SIADH: Syndrome of inappropriate antidiuretic hormone secretion CHF: Congestive heart failure COPD: Chronic obstructive pulmonary disease

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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule
Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule
Overall Number of Participants Analyzed 28 30
Measure Type: Number
Unit of Measure: Participants
Infusion Site Reaction - No assessment 0 1
Infusion Site Reaction - 0 17 16
Infusion Site Reaction - 1+ 5 7
Infusion Site Reaction - 2+ 2 0
Infusion Site Reaction - 3+ 4 5
Infusion Site Reaction - 4+ 0 1
Hide 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 [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.37 to 0.83
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 28 29 30 29
Mean (Standard Deviation)
Unit of Measure: mmol/L
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 28 29 30 29
Mean (Standard Deviation)
Unit of Measure: hr * mEq/L
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo loading dose + 20 mg/day continuous infusion conivaptan per premix bag
Overall Number of Participants Analyzed 30
Median (Inter-Quartile Range)
Unit of Measure: Hours
24.08
(16.00 to 40.50)
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 28 29 30 29
Measure Type: Number
Unit of Measure: Participants
0 - 24.5 Hours 6 13 13 10
0 - 48.5 Hours 13 15 23 19
0 - 96.5 Hours 21 22 27 24
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 28 29 30 29
Measure Type: Number
Unit of Measure: Participants
0 - 24.5 Hours 1 6 7 6
0 - 48.5 Hours 6 13 17 12
0 - 96.5 Hours 13 16 24 19
Time Frame [Not Specified]
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/28 (7.14%)   5/30 (16.67%)   8/30 (26.67%)   2/29 (6.90%) 
Cardiac disorders         
Cardiac failure congestive  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Intestinal obstruction  1  0/28 (0.00%)  0/30 (0.00%)  0/30 (0.00%)  1/29 (3.45%) 
Hepatobiliary disorders         
Bile duct obstruction  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Infections and infestations         
Bacteraemia  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Cellulitis  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Pneumonia  1  0/28 (0.00%)  1/30 (3.33%)  0/30 (0.00%)  0/29 (0.00%) 
Urinary tract infection  1  1/28 (3.57%)  1/30 (3.33%)  0/30 (0.00%)  0/29 (0.00%) 
Injury, poisoning and procedural complications         
Collapse of lung  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Metabolism and nutrition disorders         
Hyponatraemia  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma  1  0/28 (0.00%)  0/30 (0.00%)  0/30 (0.00%)  1/29 (3.45%) 
Bladder cancer  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Neoplasm malignant  1  0/28 (0.00%)  1/30 (3.33%)  0/30 (0.00%)  0/29 (0.00%) 
Ovarian cancer metastatic  1  0/28 (0.00%)  1/30 (3.33%)  0/30 (0.00%)  0/29 (0.00%) 
Renal and urinary disorders         
Renal failure  1  0/28 (0.00%)  1/30 (3.33%)  1/30 (3.33%)  0/29 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pleural effusion  1  0/28 (0.00%)  1/30 (3.33%)  0/30 (0.00%)  0/29 (0.00%) 
Pulmonary congestion  1  0/28 (0.00%)  1/30 (3.33%)  0/30 (0.00%)  0/29 (0.00%) 
Pulmonary embolism  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Respiratory distress  1  1/28 (3.57%)  0/30 (0.00%)  0/30 (0.00%)  0/29 (0.00%) 
Surgical and medical procedures         
Haemodialysis  1  0/28 (0.00%)  0/30 (0.00%)  1/30 (3.33%)  0/29 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dose Regimen 1 Dose Regimen 2 Dose Regimen 3 Dose Regimen 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/28 (21.43%)   12/30 (40.00%)   4/30 (13.33%)   8/29 (27.59%) 
Blood and lymphatic system disorders         
Anaemia  1  0/28 (0.00%)  4/30 (13.33%)  0/30 (0.00%)  0/29 (0.00%) 
Gastrointestinal disorders         
Constipation  1  3/28 (10.71%)  5/30 (16.67%)  2/30 (6.67%)  0/29 (0.00%) 
Diarrhoea  1  0/28 (0.00%)  6/30 (20.00%)  0/30 (0.00%)  4/29 (13.79%) 
General disorders         
Chest pain  1  2/28 (7.14%)  0/30 (0.00%)  2/30 (6.67%)  0/29 (0.00%) 
Pyrexia  1  0/28 (0.00%)  0/30 (0.00%)  0/30 (0.00%)  2/29 (6.90%) 
Metabolism and nutrition disorders         
Hyperkalaemia  1  0/28 (0.00%)  2/30 (6.67%)  0/30 (0.00%)  0/29 (0.00%) 
Hypokalaemia  1  0/28 (0.00%)  0/30 (0.00%)  0/30 (0.00%)  4/29 (13.79%) 
Nervous system disorders         
Headache  1  3/28 (10.71%)  0/30 (0.00%)  0/30 (0.00%)  0/29 (0.00%) 
Somnolence  1  0/28 (0.00%)  2/30 (6.67%)  0/30 (0.00%)  0/29 (0.00%) 
Vascular disorders         
Hypotension  1  0/28 (0.00%)  0/30 (0.00%)  0/30 (0.00%)  2/29 (6.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Senior Medial Director, Medical Affairs
Organization: Astellas Pharma Global Development
EMail: clinicaltrials@us.astellas.com
Layout table for additonal information
Responsible Party: Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00435591    
Other Study ID Numbers: 087-CL-084
First Submitted: February 14, 2007
First Posted: February 15, 2007
Results First Submitted: April 28, 2010
Results First Posted: May 26, 2010
Last Update Posted: May 15, 2014