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

Primary Purpose

Hyponatremia, Euvolemia, Hypervolemia

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Conivaptan
placebo
Sponsored by
Cumberland Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyponatremia focused on measuring Hyponatremia, Euvolemia, Hypervolemia, Conivaptan, Vaprisol®, YM087

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Regimen 1

Dose Regimen 2

Dose Regimen 3

Dose Regimen 4

Arm 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

Outcomes

Primary Outcome Measures

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
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

Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period
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.
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
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 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
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.
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
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.
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
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.

Full Information

First Posted
February 14, 2007
Last Updated
April 30, 2014
Sponsor
Cumberland Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00435591
Brief Title
A Study of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia
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 Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cumberland Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyponatremia, Euvolemia, Hypervolemia
Keywords
Hyponatremia, Euvolemia, Hypervolemia, Conivaptan, Vaprisol®, YM087

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
121 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Regimen 1
Arm Type
Experimental
Arm Description
Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule
Arm Title
Dose Regimen 2
Arm Type
Experimental
Arm Description
Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule
Arm Title
Dose Regimen 3
Arm Type
Experimental
Arm Description
Placebo loading dose + 20mg/day continuous infusion conivaptan per premix bag
Arm Title
Dose Regimen 4
Arm Type
Experimental
Arm Description
Conivaptan loading dose (20mg) + 20mg/day continuous infusion conivaptan per premix bag
Intervention Type
Drug
Intervention Name(s)
Conivaptan
Other Intervention Name(s)
YM087, Vaprisol
Intervention Description
ampoule or premix bag
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
ampoule or premix bag
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Art Wheeler, MD
Organizational Affiliation
Cumberland Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
City
Bangalore
ZIP/Postal Code
560034
Country
India
City
Bangalore
ZIP/Postal Code
560099
Country
India
City
Bhopal
ZIP/Postal Code
462001
Country
India
City
Hyderabaad
ZIP/Postal Code
500482
Country
India
City
Karnal
ZIP/Postal Code
132001
Country
India
City
Afula
ZIP/Postal Code
18101
Country
Israel
City
Ashkelon
ZIP/Postal Code
78308
Country
Israel
City
Haifa
ZIP/Postal Code
31048
Country
Israel
City
Haifa
ZIP/Postal Code
34362
Country
Israel
City
Holon
ZIP/Postal Code
58100
Country
Israel
City
Jerusalem
ZIP/Postal Code
910301
Country
Israel
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
City
Rechovot
ZIP/Postal Code
76100
Country
Israel
City
Safed
ZIP/Postal Code
13100
Country
Israel
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
City
Zerifin
ZIP/Postal Code
70300
Country
Israel

12. IPD Sharing Statement

Citations:
PubMed Identifier
21411800
Citation
Kalra S, Efrati S, Arthur JM, Oliven A, Velez JC, McNutt BE, Klasen S, Abeyratne A. Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia. Am J Health Syst Pharm. 2011 Apr 1;68(7):590-8. doi: 10.2146/ajhp100243.
Results Reference
background
Links:
URL
http://www.astellas.us/docs/vaprisol.pdf
Description
Link to Prescribing Information

Learn more about this trial

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

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