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

Phase 3

Completed

• Conditions: Hyponatremia
• Interventions: Drug: Conivaptan; Drug: Placebo

• Registration Number: NCT00478192
• Lead Sponsor: Cumberland Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04
• Study First Submitted: 2007-05-22
• Study First Submitted QC: 2007-05-22
• Study First Posted: 2007-05-24
• Primary Completion: 2008-08
• Study Completion: 2008-08
• Results First Submitted: 2010-03-31
• Results First Submitted QC: 2010-03-31
• Results First Posted: 2010-04-21
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-30
• Last Update Posted: 2014-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen 1 Conivaptan QD	Conivaptan	20 mg conivaptan once a day
Regimen 2 Conivaptan BID	Conivaptan	20 mg conivaptan two times a day
Regimen 3 Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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.
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.
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.
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
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
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