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

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

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

Study Overview

• Status: Completed
• Conditions: Hyponatremia
• Intervention / Treatment: Drug: Conivaptan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Coimbatore, India, 641014
  • Indore, India, 452014
  • Jaipur, India, 302013
  • Karnal, India, 132001
  • Visakhapatnam, India, 530002
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
  • Arizona
    • Tucson, Arizona, United States, 85723
  • California
    • Los Angeles, California, United States, 90073
  • Colorado
    • Denver, Colorado, United States, 80218
  • Florida
    • Jacksonville, Florida, United States, 32216
    • Port Charlotte, Florida, United States, 33952
  • Illinois
    • Chicago, Illinois, United States, 60612
  • Indiana
    • Indianapolis, Indiana, United States, 46260
  • Kentucky
    • Hazard, Kentucky, United States, 41701
  • Michigan
    • Detroit, Michigan, United States, 48201
  • Nebraska
    • Omaha, Nebraska, United States, 68198
  • New York
    • Bronx, New York, United States, 10461
  • Ohio
    • Cincinnati, Ohio, United States, 45267
    • Fairfield, Ohio, United States, 45014
    • Toledo, Ohio, United States, 43606
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19107
    • Philadelphia, Pennsylvania, United States, 19140
    • Philadelphia, Pennsylvania, United States, 19102
  • South Carolina
    • Charleston, South Carolina, United States, 29425
    • Orangeburg, South Carolina, United States, 29118

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48
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.	48 Hours
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.	48 Hours
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.	48 Hours
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	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	Baseline, Hour 12, Hour 24,Hour 36 and Hour 48
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	Baseline, Hour 24 and Hour 48

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to Prescribing Information

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: May 22, 2007
• First Submitted That Met QC Criteria: May 22, 2007
• First Posted (Estimate): May 24, 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; conivaptan; hypervolemic; euvolemic; edematous
• 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-088