A Study of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia - Full Text View

Sponsor:	Astellas Pharma Inc
Information provided by:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT00435591

Purpose

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

Condition	Intervention	Phase
Hyponatremia Euvolemia Hypervolemia	Drug: Conivaptan Drug: placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: YM 087 Conivaptan

U.S. FDA Resources

Further study details as provided by Astellas Pharma Inc:

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 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: 24.5 hours, 48.5 hours and 96.5 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 48.5 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours ] [ Designated as safety issue: No ]
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 [ Time Frame: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours ] [ Designated as safety issue: No ]
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.

Enrollment:	121
Study Start Date:	January 2007
Study Completion Date:	September 2008
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dose Regimen 1 Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule	Drug: Conivaptan ampoule or premix bag Other Names: YM087 Vaprisol Drug: placebo ampoule or premix bag
Experimental: Dose Regimen 2 Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule	Drug: Conivaptan ampoule or premix bag Other Names: YM087 Vaprisol
Experimental: Dose Regimen 3 Placebo loading dose + 20mg/day continuous infusion conivaptan per premix bag	Drug: Conivaptan ampoule or premix bag Other Names: YM087 Vaprisol Drug: placebo ampoule or premix bag
Experimental: Dose Regimen 4 Conivaptan loading dose (20mg) + 20mg/day continuous infusion conivaptan per premix bag	Drug: Conivaptan ampoule or premix bag Other Names: YM087 Vaprisol

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00435591

Locations

United States, South Carolina

Charleston, South Carolina, United States, 29425
India

Bangalore, India, 560034

Bangalore, India, 560099

Bhopal, India, 462001

Hyderabaad, India, 500482

Karnal, India, 132001
Israel

Afula, Israel, 18101

Ashkelon, Israel, 78308

Haifa, Israel, 31048

Haifa, Israel, 34362

Holon, Israel, 58100

Jerusalem, Israel, 910301

Jerusalem, Israel, 91120

Rechovot, Israel, 76100

Safed, Israel, 13100

Tel Hashomer, Israel, 52621

Tel-Aviv, Israel, 64239

Zerifin, Israel, 70300

Sponsors and Collaborators

Astellas Pharma Inc

Investigators

Study Director:

Central Contact

Astellas Pharma US, Inc.

More Information

Additional Information:

Link to Prescribing Information This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Sr Manager Clinical Trial Registry, Astellas Pharma US, Inc
ClinicalTrials.gov Identifier:	NCT00435591 History of Changes
Other Study ID Numbers:	087-CL-084
Study First Received:	February 14, 2007
Results First Received:	April 28, 2010
Last Updated:	April 15, 2011
Health Authority:	United States: Food and Drug Administration; Israel: Ministry of Health; India: Drugs Controller General of India

Keywords provided by Astellas Pharma Inc:

Hyponatremia
Euvolemia
Hypervolemia

Conivaptan
Vaprisol®
YM087

Additional relevant MeSH terms:

Hyponatremia
Water Intoxication
Water-Electrolyte Imbalance

Metabolic Diseases
Poisoning
Substance-Related Disorders

ClinicalTrials.gov processed this record on February 13, 2012