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

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

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

Study Overview

• Status: Completed
• Conditions: Hyponatremia; Euvolemia; Hypervolemia
• Intervention / Treatment: Drug: Conivaptan; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 4

Contacts and Locations

Study Locations

• 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, 91120
  • Jerusalem, Israel, 910301
  • Rechovot, Israel, 76100
  • Safed, Israel, 13100
  • Tel Hashomer, Israel, 52621
  • Tel-Aviv, Israel, 64239
  • Zerifin, Israel, 70300
• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Study Director: Art Wheeler, MD, Cumberland Pharmaceuticals, Inc.

Publications and helpful links

General 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. doi: 10.2146/ajhp100243.

Helpful Links

• Link to Prescribing Information

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: February 14, 2007
• First Submitted That Met QC Criteria: February 14, 2007
• First Posted (Estimate): February 15, 2007

Study Record Updates

• Last Update Posted (Estimate): May 15, 2014
• Last Update Submitted That Met QC Criteria: April 30, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Hyponatremia; Euvolemia; Hypervolemia; Conivaptan; Vaprisol®; YM087
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Conivaptan
• Other Study ID Numbers: 087-CL-084

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No