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

Primary Purpose

Hyponatremia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Conivaptan
Placebo
Sponsored by
Cumberland Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyponatremia focused on measuring hyponatremia, hypervolemic, euvolemic, edematous, conivaptan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Regimen 1 Conivaptan QD

Regimen 2 Conivaptan BID

Regimen 3 Placebo

Arm Description

20 mg conivaptan once a day

20 mg conivaptan two times a day

Outcomes

Primary Outcome Measures

Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
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
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
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
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
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
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
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
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

Full Information

First Posted
May 22, 2007
Last Updated
April 30, 2014
Sponsor
Cumberland Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00478192
Brief Title
Study of Efficacy & Safety for 3 Infusion Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia
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 Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cumberland Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyponatremia
Keywords
hyponatremia, hypervolemic, euvolemic, edematous, conivaptan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Regimen 1 Conivaptan QD
Arm Type
Experimental
Arm Description
20 mg conivaptan once a day
Arm Title
Regimen 2 Conivaptan BID
Arm Type
Experimental
Arm Description
20 mg conivaptan two times a day
Arm Title
Regimen 3 Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Conivaptan
Other Intervention Name(s)
YM087, Vaprisol
Intervention Description
premix bag
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
premix bag
Primary Outcome Measure Information:
Title
Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
Description
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.
Time Frame
Baseline and 48 hours
Secondary Outcome Measure Information:
Title
Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment
Description
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 Frame
Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48
Title
Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium
Description
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.
Time Frame
48 Hours
Title
Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours
Description
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.
Time Frame
48 Hours
Title
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
Description
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.
Time Frame
48 Hours
Title
Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours
Description
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
Time Frame
48 Hours
Title
Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment
Description
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
Time Frame
Baseline, Hour 12, Hour 24,Hour 36 and Hour 48
Title
Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment
Description
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
Time Frame
Baseline, Hour 24 and Hour 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Art Wheeler, MD
Organizational Affiliation
Cumberland Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85723
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
City
Hazard
State/Province
Kentucky
ZIP/Postal Code
41701
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
City
Fairfield
State/Province
Ohio
ZIP/Postal Code
45014
Country
United States
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
City
Coimbatore
ZIP/Postal Code
641014
Country
India
City
Indore
ZIP/Postal Code
452014
Country
India
City
Jaipur
ZIP/Postal Code
302013
Country
India
City
Karnal
ZIP/Postal Code
132001
Country
India
City
Visakhapatnam
ZIP/Postal Code
530002
Country
India

12. IPD Sharing Statement

Citations:
PubMed Identifier
21515866
Citation
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.
Results Reference
background
Links:
URL
http://www.astellas.us/docs/vaprisol.pdf
Description
Link to Prescribing Information

Learn more about this trial

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

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