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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hyponatremia	Drug: Conivaptan; Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	50 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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 Hypervolemic Hyponatremia
Study Start Date :	April 2007
Actual Primary Completion Date :	August 2008
Actual Study Completion Date :	August 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Regimen 1 Conivaptan QD; 20 mg conivaptan once a day	Drug: Conivaptan; premix bag; Other Names: YM087; Vaprisol
Experimental: Regimen 2 Conivaptan BID; 20 mg conivaptan two times a day	Drug: Conivaptan; premix bag; Other Names: YM087; Vaprisol
Placebo Comparator: Regimen 3 Placebo	Drug: Placebo; premix bag

Outcome Measures

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Primary Outcome Measures :

1. Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. [ Time Frame: 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 :

1. 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

2. 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.

3. 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.
4. 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.
5. 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

6. 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

7. 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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 26 Study Locations

Sponsors and Collaborators

Cumberland Pharmaceuticals

Investigators

Study Director:	Art Wheeler, MD	Cumberland Pharmaceuticals Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Link to Prescribing Information 

Publications:

Koren MJ, Hamad A, Klasen S, Abeyratne A, McNutt BE, Kalra S. Efficacy and safety of 30-minute infusions of conivaptan in euvolemic and hypervolemic hyponatremia. Am J Health Syst Pharm. 2011 May 1;68(9):818-27. doi: 10.2146/ajhp100260. Erratum in: Am J Health Syst Pharm. 2011 Aug 1;68(15):1374.

Responsible Party:	Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00478192 History of Changes
Other Study ID Numbers:	087-CL-088
First Posted:	May 24, 2007
Results First Posted:	April 21, 2010
Last Update Posted:	May 15, 2014
Last Verified:	April 2014

Keywords provided by Cumberland Pharmaceuticals:

hyponatremia; hypervolemic; euvolemic; edematous; conivaptan

Additional relevant MeSH terms:

Hyponatremia; Water-Electrolyte Imbalance; Metabolic Diseases; Conivaptan	Antidiuretic Hormone Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Physiological Effects of Drugs