HyponatremiaPhase 3NCT00478192

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

A Phase 3 study testing Conivaptan in people with Hyponatremia, run by Cumberland Pharmaceuticals at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Hyponatremia
What is being tested?: Conivaptan
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 50 participants
Where: 26 sitesin 2 countries
Study dates: Apr 2007to Aug 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Euvolemic or hypervolemic (edematous) based on clinical presentation
Serum sodium between 115 and 130mEq/L at baseline

Who cannot join

Clinical presentation of volume depletion or dehydration

Trial locations and contacts

26 sites in 2 countries.

Country

City, postcode or hospital

26 sites in 2 countries

United States21 sites

Study site
Charleston, South Carolina, 29425
Study site
Chicago, Illinois, 60612
Study site
Cincinnati, Ohio, 45267
Study site
Denver, Colorado, 80218
Study site
Detroit, Michigan, 48201
Study site
Fairfield, Ohio, 45014
Study site
Hazard, Kentucky, 41701
Study site
Huntsville, Alabama, 35801
Study site
Indianapolis, Indiana, 46260
Study site
Jacksonville, Florida, 32216
Study site
Los Angeles, California, 90073
Study site
Omaha, Nebraska, 68198
Study site
Orangeburg, South Carolina, 29118
Study site
Philadelphia, Pennsylvania, 19102
Study site
Philadelphia, Pennsylvania, 19104
Study site
Philadelphia, Pennsylvania, 19107
Study site
Philadelphia, Pennsylvania, 19140
Study site
Port Charlotte, Florida, 33952
Study site
The Bronx, New York, 10461
Study site
Toledo, Ohio, 43606
Study site
Tucson, Arizona, 85723

Other trials in United States

India5 sites

Study site
Coimbatore, 641014
Study site
Indore, 452014
Study site
Jaipur, 302013
Study site
Karnāl, 132001
Study site
Visakhapatnam, 530002

Other trials in India

About this study

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

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

Conditions: Hyponatremia
Being tested: Conivaptan, Placebo
Keywords: hyponatremia, hypervolemic, euvolemic, edematous, conivaptan
Medical subject headings: Hyponatremia, Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ConivaptanDrug
Also called YM087, Vaprisol
premix bag
PlaceboDrug
premix bag

Study groups in NCT00478192
Study group	Role	What they receive
Regimen 1 Conivaptan QD	Experimental	20 mg conivaptan once a day Receives: Drug: Conivaptan
Regimen 2 Conivaptan BID	Experimental	20 mg conivaptan two times a day Receives: Drug: Conivaptan
Regimen 3 Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and 48 hours

Secondary outcomes (7)

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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline, Hour 24 and Hour 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2007Aug 2008

First posted24 May 2007 (estimated)
Study startApr 2007
Primary completionAug 2008
Study completionAug 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HyponatremiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00478192
Sponsor's protocol ID: 087-CL-088
Status last verified: Apr 2014
First submitted: 22 May 2007
Last updated: 15 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 21515866

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia
Hyponatremia
Enrolling by invitationObservational study
International Multi-center Retrospective Study of Patients With Serum Sodium ≤110 mmol/L to Determine the Relationship Between Osmotic Demyelination Syndrome (ODS) and Rapid Correction of Hyponatremia
Hyponatremia Symptomatic, Osmotic Demyelination Syndrome
Active, not recruitingObservational study
Samsca Post-marketing General Drug Use-results Survey in Patients With Hyponatremia in SIADH
Antidiuretic Hormone, Inappropriate Secretion
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Active, not recruitingObservational study
Hyponatremia - Complications, Prognosis, Epidemiology in Finnish Tertiary Care
Hyponatremia, Osmotic Demyelination Syndrome

All Hyponatremia trials

Study at a glance

From the registry record, last updated by the sponsor on 15 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00478192
Acronym / sponsor ID: 087-CL-088
Conditions: Hyponatremia
Keywords: hyponatremia, hypervolemic, euvolemic, edematous, conivaptan
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Cumberland PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Apr 2007
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 24 May 2007 (estimated)
Results: Posted 21 Apr 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Regimen 1 Conivaptan QD	Experimental	Drug: Conivaptan20 mg conivaptan once a day
Regimen 2 Conivaptan BID	Experimental	Drug: Conivaptan20 mg conivaptan two times a day
Regimen 3 Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Euvolemic or hypervolemic (edematous) based on clinical presentation
Serum sodium between 115 and 130mEq/L at baseline

Key exclusion criteria (1 listed)

Clinical presentation of volume depletion or dehydration

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ConivaptanAlso: YM087, Vaprisolpremix bag	Drug	Regimen 1 Conivaptan QD, Regimen 2 Conivaptan BID
Placebopremix bag	Drug	Regimen 3 Placebo

Primary outcome

Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
Time frame: Baseline and 48 hours
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.

7 secondary outcomes

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
Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium
Time frame: 48 Hours
Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours
Time frame: 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
Time frame: 48 Hours
Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours
Time frame: 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
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

Results and safety

Results posted to the registry on 21 Apr 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Regimen 1 Conivaptan QD	20	16
Regimen 2 Conivaptan BID	20	15
Regimen 3 Placebo	10	8

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

Time frame: Baseline and 48 hours. Mean (Standard Deviation). Unit: mEq/L

Measure	Regimen 1 Conivaptan QD n = 20	Regimen 2 Conivaptan BID n = 20	Regimen 3 Placebo n = 9
Baseline (N= 20; 20; 9)	126.03 (4.017)	126.39 (3.581)	125.55 (3.648)
Hour 48 (N=19; 17; 8)	130.4 (5.21)	133.4 (4.82)	127.6 (2.36)
Change from Baseline (N=19; 17; 8)	4.00 (3.80)	7.36 (4.04)	1.16 (2.86)

Regimen 1 Conivaptan QD vs Regimen 2 Conivaptan BID: p = 0.028, ANCOVA
Regimen 1 Conivaptan QD vs Regimen 3 Placebo: p = 0.019, ANCOVA
Regimen 2 Conivaptan BID vs Regimen 3 Placebo: p <0.001, ANCOVA

Population analysed: Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and who had baseline serum sodium data. The number of participants analyzed per arm represents FAS. The numbers of participants for each visit are noted in the category titles.

7 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Regimen 1 Conivaptan QD	6 of 20 (30%)	7 of 20 (35%)	Not reported
Regimen 2 Conivaptan BID	5 of 20 (25%)	10 of 20 (50%)	Not reported
Regimen 3 Placebo	2 of 9 (22.2%)	5 of 9 (55.6%)	Not reported

Limitations and caveats (from the sponsor): Company makes no warranties or representations of any kind as to the currency or completeness of the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose and shall not be liable for any damages.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21515866Koren 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.
Link to Prescribing InformationLink provided by the sponsor.

Related trials for Hyponatremia

RecruitingPhase 3
Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia
Hyponatremia
Enrolling by invitationObservational study
International Multi-center Retrospective Study of Patients With Serum Sodium ≤110 mmol/L to Determine the Relationship Between Osmotic Demyelination Syndrome (ODS) and Rapid Correction of Hyponatremia
Hyponatremia Symptomatic, Osmotic Demyelination Syndrome
Active, not recruitingObservational study
Samsca Post-marketing General Drug Use-results Survey in Patients With Hyponatremia in SIADH
Antidiuretic Hormone, Inappropriate Secretion
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Active, not recruitingObservational study
Hyponatremia - Complications, Prognosis, Epidemiology in Finnish Tertiary Care
Hyponatremia, Osmotic Demyelination Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Art Wheeler, MD study director

Cumberland Pharmaceuticals

26 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Conivaptan in people with Hyponatremia, run by Cumberland Pharmaceuticals at 26 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation. (time frame: Baseline and 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00478192, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2014.