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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase IIIb, Randomized, Double-Blind, Parallel Group, Multi-Center, Study to Assess the Efficacy and Safety of Multiple 30 Minute Infusions of YM087 (Conivaptan) in Subjects With Euvolemic or Hyperv

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 Summary:
Sponsor: Cumberland Pharmaceuticals

Current Primary Outcome: Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. [ Time Frame: Baseline and 48 hours ]

Original Primary Outcome: Change in serum sodium from Baseline. Safety of each dosing regimen

Current Secondary Outcome:

• Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome:

Information By: Cumberland Pharmaceuticals

Dates:
Date Received: May 22, 2007
Date Started: April 2007
Date Completion:
Last Updated: April 30, 2014
Last Verified: April 2014