HyponatremiaPhase 3NCT01451411
A Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
A Phase 3 study testing Conivaptan hydrochloride in people with Hyponatremia, run by Cumberland Pharmaceuticals at 3 sites in 2 countries.
Trial summary
The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of intravenous conivaptan in pediatric subjects with abnormally low concentration of sodium in blood. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Hyponatremia
- What is being tested?
- Conivaptan hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2012to Jan 2014
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subject is euvolemic or hypervolemic hyponatremia upon clinical presentation
- Subject has serum sodium value ≥ 115 mEq/L (115 mmol/L) and < 130 mEq/L (130 mmol/L) during the 24 hours preceding inclusion into the study
- Female subject of childbearing potential must have a negative serum pregnancy test and must be premenarchal, surgically sterile or must practice a method of birth control
Who cannot join
- Female subject is pregnant or lactating
- Subject has a body mass index (BMI) < the 3rd percentile or > the 97th percentile for their age and stature according to the World Health Organization; Body mass index-for-age percentiles charts for boys and girls ages 2 to 20
- Subject has clinical evidence of volume depletion, dehydration or hypovolemia
- Subject with hypovolemic hyponatremia or transient causes of hyponatremia that are likely to resolve during the time of study participation
- Subjects with a cause of hyponatremia that is most appropriately corrected by alternative therapies
- Subject is expected to receive emergent treatment for hyponatremia during the treatment period of the study
Show all 23Show fewer
- Subject has clinical evidence of hypotension
- Subject has uncontrolled hypertension > the 99th percentile for their age
- Subject has uncontrolled bradyarrhythmias or tachyarrhythmias requiring emergent pacemaker placement or treatment
- Subject has untreated severe hypothyroidism, hyperthyroidism or adrenal insufficiency
- Subject has known urinary outflow obstruction, unless subject is, or can be catheterized during the study
- Subject has estimated creatinine clearance < 30 mL/min during the seven days prior to study drug administration
- Subject has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations > 3 times the upper limit of normal reference range during the seven days prior to study drug administration
- Subject has serum albumin ≤ 1.5 g/dL during the seven days prior to study drug administration
- Subject has white blood cell count (WBC) < 3000/micro-liter documented any time during seven days prior to study drug administration or anticipated drop in WBC to < 3000/micro-liter during the period of the study due to chemotherapy
- Subject currently has unstable hepatic function or a history of hepatic encephalopathy, or bleeding esophageal varices within the last 3 months
- Subject has acute heart failure. Prior history of heart failure is allowed if there are no current signs/symptoms
- Subject has a non-fasting blood glucose value ≥ 275 mg/dL
- Subject requires or is suspected to require treatment with potent inhibitors or potent inducers of CYP3A4
- Subject was administered hypertonic saline or oral salt supplement within 24 hours prior to study drug administration
- Subject requires the use of medications used in the treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): including lithium salts, urea or demeclocycline during the week prior to screening and throughout the study drug treatment period
- Subject has any condition that may interfere with treatment or evaluation of safety
- Subject has received investigational therapy (including placebo) within 28 days or 5 half lives, whichever is longer
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Colombia2 sites
Fundación Cardioinfantil - Instituto Cardiológico
Bogotá
Fundación Valle del Lili
Cali, Valle
United States1 site
Children's Hospital of New York - Presbyterian
New York, New York, 10032
About this study
Official title: A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center, Dose-Titration Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of intravenous conivaptan in pediatric subjects with abnormally low concentration of sodium in blood.
Read the detailed description
A 3:1 randomization between conivaptan and placebo will be implemented and randomization will be further stratified in a 1:1:2 ratio for age groups: 2-5 years, 6-10 years, and 11-17 years.
Subjects will need to remain hospitalized for the 48-hour Treatment Period through Hour 96 (Day 4). There will be a follow-up safety visit on Day 9 or day of hospital discharge, whichever occurs first. There is a final follow-up phone call at Day 32 to assess if any serious adverse events have occurred since hospital discharge.
- Conditions
- Hyponatremia
- Being tested
- Conivaptan hydrochloride, Placebo
- Keywords
- Serum Sodium, Euvolemia, Hypervolemia, Vaprisol®, Conivaptan, YM087
- Medical subject headings
- Hyponatremia, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conivaptan hydrochlorideDrug
Also called Vaprisol®, YM087
Intravenous
PlaceboDrug
Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Conivaptan hydrochloride | Experimental | Not described Receives: Drug: Conivaptan hydrochloride |
| 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.
Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium
Measured: baseline and 48 hours
Secondary outcomes (8)
Time From the First Dose of Study Medication to a Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
Measured: 48 hours
Number of Patients With Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
Measured: baseline and 48 hours
Number of Subjects With Confirmed > 6 mEq/L Increase From Baseline in Serum Sodium or a Confirmed Normal Serum Sodium Level (Greater Than or Equal to 135 mEq/L)
Measured: baseline and 48 hours
Change From Baseline in Effective Water Clearance (EWC) Every 12 Hours
Measured: Baseline, Hours 12, 24, 36 and 48
Change From Baseline in Free Water Clearance (FWC)
Measured: Baseline and 48 hours
Number of Participants With an Overly Rapid Rise in Serum Sodium From Baseline
an absolute serum sodium of 145 mEq/L at Hour 24 or an increase in serum sodium of greater than 12 mEq/L
Measured: baseline and Hours 3, 8, 12 and 24.
Population Pharmacokinetics: Clearance (CL)
Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median CL
Measured: Up to Hour 60
Population Pharmacokinetics: Volume of Distribution (Vd)
Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median Vd
Measured: Up to Hour 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2011 (estimated)
- Study startFeb 2012
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Enrollment goals were not met.
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.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cumberland Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Art Wheeler, MD, Study director, Cumberland Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451411
- Sponsor's protocol ID
- 087-CL-096
- Status last verified
- Feb 2016
- First submitted
- 5 Oct 2011
- Last updated
- 1 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center, Dose-Titration Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
- ClinicalTrials.gov ID
- NCT01451411
- Acronym / sponsor ID
- 087-CL-096
- Conditions
- Hyponatremia
- Keywords
- Serum Sodium, Euvolemia, Hypervolemia, Vaprisol®, Conivaptan, YM087
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment goals were not met.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Cumberland PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 13 Oct 2011 (estimated)
- Results
- Posted 1 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of intravenous conivaptan in pediatric subjects with abnormally low concentration of sodium in blood.
Detailed description
A 3:1 randomization between conivaptan and placebo will be implemented and randomization will be further stratified in a 1:1:2 ratio for age groups: 2-5 years, 6-10 years, and 11-17 years.
Subjects will need to remain hospitalized for the 48-hour Treatment Period through Hour 96 (Day 4). There will be a follow-up safety visit on Day 9 or day of hospital discharge, whichever occurs first. There is a final follow-up phone call at Day 32 to assess if any serious adverse events have occurred since hospital discharge.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conivaptan hydrochloride | Experimental | Drug: Conivaptan hydrochloride |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Subject is euvolemic or hypervolemic hyponatremia upon clinical presentation
- Subject has serum sodium value ≥ 115 mEq/L (115 mmol/L) and < 130 mEq/L (130 mmol/L) during the 24 hours preceding inclusion into the study
- Female subject of childbearing potential must have a negative serum pregnancy test and must be premenarchal, surgically sterile or must practice a method of birth control
Key exclusion criteria (23 listed)
- Female subject is pregnant or lactating
- Subject has a body mass index (BMI) < the 3rd percentile or > the 97th percentile for their age and stature according to the World Health Organization; Body mass index-for-age percentiles charts for boys and girls ages 2 to 20
- Subject has clinical evidence of volume depletion, dehydration or hypovolemia
- Subject with hypovolemic hyponatremia or transient causes of hyponatremia that are likely to resolve during the time of study participation
- Subjects with a cause of hyponatremia that is most appropriately corrected by alternative therapies
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 |
|---|---|---|
| Conivaptan hydrochlorideAlso: Vaprisol®, YM087Intravenous | Drug | Conivaptan hydrochloride |
| PlaceboIntravenous | Drug | Placebo |
Primary outcome
Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium
Time frame: baseline and 48 hours
8 secondary outcomes
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 ≥ 4 mEq/L Increase From Baseline in Serum Sodium
Time frame: baseline and 48 hours
Number of Subjects With Confirmed > 6 mEq/L Increase From Baseline in Serum Sodium or a Confirmed Normal Serum Sodium Level (Greater Than or Equal to 135 mEq/L)
Time frame: baseline and 48 hours
Change From Baseline in Effective Water Clearance (EWC) Every 12 Hours
Time frame: Baseline, Hours 12, 24, 36 and 48
Change From Baseline in Free Water Clearance (FWC)
Time frame: Baseline and 48 hours
Number of Participants With an Overly Rapid Rise in Serum Sodium From Baseline
Time frame: baseline and Hours 3, 8, 12 and 24.
Population Pharmacokinetics: Clearance (CL)
Time frame: Up to Hour 60
Population Pharmacokinetics: Volume of Distribution (Vd)
Time frame: Up to Hour 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hyponatremia
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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
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Active, not recruitingObservational study
Hyponatremia - Complications, Prognosis, Epidemiology in Finnish Tertiary Care
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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
3 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 hydrochloride in people with Hyponatremia, run by Cumberland Pharmaceuticals at 3 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 3 inclusion and 23 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: stopped early, as of the sponsor's last update on 1 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Colombia, United States. 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 1 Mar 2016). 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?
Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium (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?
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 1 Mar 2016.