Study of Efficacy & Safety for 3 Infusion 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:
NCT00478192
First received: May 22, 2007
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Hyponatremia
Drug: Conivaptan
Drug: Placebo
Phase 3

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 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

Resource links provided by NLM:


Further study details as provided by Cumberland Pharmaceuticals:

Primary Outcome Measures:
  • Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. [ Time Frame: Baseline and 48 hours ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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



Enrollment: 50
Study Start Date: April 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT00478192

  Show 26 Study Locations
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: NCT00478192     History of Changes
Other Study ID Numbers: 087-CL-088
Study First Received: May 22, 2007
Results First Received: March 31, 2010
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration
India: Drugs Controller General of India

Keywords provided by Cumberland Pharmaceuticals:
hyponatremia
hypervolemic
euvolemic
edematous
conivaptan

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

ClinicalTrials.gov processed this record on August 27, 2014