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

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

Official Title
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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

Conditions
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Hyponatremia, Euvolemia, Hypervolemia

Intervention / Treatment
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* Drug: Conivaptan
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Regimen 1<br>Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule | Drug: Conivaptan<br>* ampoule or premix bag<br>* Other names: Vaprisol;Drug: placebo<br>* ampoule or premix bag<br>|
| Experimental: Dose Regimen 2<br>Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule | Drug: Conivaptan<br>* ampoule or premix bag<br>* Other names: Vaprisol;|
| Experimental: Dose Regimen 3<br>Placebo loading dose + 20mg/day continuous infusion conivaptan per premix bag | Drug: Conivaptan<br>* ampoule or premix bag<br>* Other names: Vaprisol;Drug: placebo<br>* ampoule or premix bag<br>|
| Experimental: Dose Regimen 4<br>Conivaptan loading dose (20mg) + 20mg/day continuous infusion conivaptan per premix bag | Drug: Conivaptan<br>* ampoule or premix bag<br>* Other names: Vaprisol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment | 
| 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. | 24.5 hours, 48.5 hours and 96.5 hours | 
| 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. | 48.5 hours | 
| 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. | 0-24.5 hours, 0-48.5 hours and 0-96.5 hours | 
| 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. | 0-24.5 hours, 0-48.5 hours and 0-96.5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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YM087, Hyponatremia, Euvolemia, Hypervolemia, Conivaptan, Vaprisol®