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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00435591
First received: February 14, 2007
Last updated: April 30, 2014
Last verified: April 2014
  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 4

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:


Further study details as provided by Cumberland Pharmaceuticals:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Cumberland Pharmaceuticals
Investigators
Study Director: Art Wheeler, MD Cumberland Pharmaceuticals Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Cumberland Pharmaceuticals
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 30, 2014
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health
India: Drugs Controller General of India

Keywords provided by Cumberland Pharmaceuticals:
Hyponatremia
Euvolemia
Hypervolemia
Conivaptan
Vaprisol®
YM087

Additional relevant MeSH terms:
Hyponatremia
Water-Electrolyte Imbalance
Metabolic Diseases

ClinicalTrials.gov processed this record on August 28, 2014