HyponatremiaPhase 3NCT02449044
International, Multicenter, Study of One-year, Open-label, Titrated Oral Tolvaptan Tablet Administration in Patients With Chronic Hyponatremia
A Phase 3 study testing Tolvaptan in people with Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc..
Trial summary
This study will assess the safety of long-term tolvaptan use in patients previously enrolled in shorter-term Phase 3 studies and gather information on the natural history of hyponatremia in the context of tolvaptan therapy and underlying disease states. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyponatremia
- What is being tested?
- Tolvaptan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- No sites listed yet
- Study dates
- May 2004to Oct 2009
- 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
- Age greater than or equal to 18 years.
- Ability to provide informed consent or assent.
- Prior successful participation in a tolvaptan hyponatremia trial termination with evidence of continued need or desire for therapy.
Who cannot join
- A current medical condition where long-term treatment with an aquaretic agent may present an undue risk to the patient.
- Hyponatremia which is acute, reversible, artifactual or due to conditions not associated with vasopressin excess or likely to respond to aquaretic therapy.
- Hyponatremia due to reversible medical condition or therapy
- Conditions associated with an independent imminent risk of morbidity and mortality
- Conditions which confound the assessment of endpoints.
About this study
Official title: International, Multicenter, Study of One-year, Open-label, Titrated Oral Tolvaptan Tablet Administration in Patients With Chronic Hyponatremia: Extension to Studies 156-02-235 and 156-03-238 to Assess One-year Safety
This study will assess the safety of long-term tolvaptan use in patients previously enrolled in shorter-term Phase 3 studies and gather information on the natural history of hyponatremia in the context of tolvaptan therapy and underlying disease states.
- Conditions
- Hyponatremia
- Being tested
- Tolvaptan
- Keywords
- Hyponatremia
- Medical subject headings
- Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Once Daily
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Experimental | Enrolled subjects began treatment with 15 mg tolvaptan QD. A titration between target doses of 15 mg, 30 mg, or 60 mg of trial medication was based on the subject's change in serum sodium concentration and clinical tolerance of the trial medication. Receives: Drug: Tolvaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With Adverse Events (AEs)
A TEAE was an AE that began after the first injection or was continuous from Baseline and was defined as any new medical problem, or exacerbation of an existing problem, whether or not it was considered drug-related by the study physician. An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-subject hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent the outcomes mentioned above.
Measured: Baseline to Post-Week 214 follow-up visit
Participants With Laboratory Values Abnormalities Reported as TEAEs
The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria. Any value outside the normal range was flagged for the attention of the study physician who was to indicate whether the value was clinically significant for identifying laboratory values of potential clinical relevance. Participants noted with abnormal laboratory values are reported below.
Measured: Baseline to Post-Week 214 follow-up visit
Participants With Electrocardiogram (ECG) Related Abnormalities Reported as TEAEs
The ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in HR outliers, PR outliers, QRS outliers, QT, QTcB, QTcF that were identified based on pre-defined criteria. Some of the pre-defined criteria for identifying ECG measurements of potential clinical relevance included: For QTcB and QTcF: baseline mean of QTcB and QTcF interval was new onset >500 msec, 30 - 60 msec, >60 msec; For QT: new onset >500 msec; For QRS outliers: >=25% change from baseline when QRS >100 msec; PR outliers: >=25% change from baseline when PR>200 msec; HR outliers: 25% decrease from baseline and HR <50 bpm or 25% increase from baseline and HR >100 bpm. New onset (>500 msec) in QT, QTcB, or QTcF means a participant who attained a value >500 msec during treatment period but not at each baseline visit. The ECG-related abnormalities are reported as TEAEs are mentioned below.
Measured: Baseline to Post-Week 214 follow-up visit
Participants With Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria. Criteria for identifying vital signs of potential clinical relevance included: Heart rate, supine: >= 120 beats per minute (bpm) + increase of ≥15 bpm from Baseline and <=50 bpm + decrease of >= 15 bpm; Diastolic Blood Pressure, Supine: >=105 mmHg + increase of >=15 mmHg and <=50 mmHg + decrease of >=15 mmHg; Systolic Blood Pressure, Supine: >=180 mmHg + increase of >=20 mmHg and <= 90 mmHg + decrease of >=20 mmHg; Temperature (degree C): Increase of >=1.1 to >=38.3C. The vital sign abnormalities were reported as TEAEs are mentioned below.
Measured: Baseline to Post-Week 214 follow-up visit
Participants With Body Weight Abnormalities Reported as TEAEs
The body weight evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Every effort was made to ensure that body weight measurements were performed in a reproducible and consistent manner. The pre-defined criteria was change of ≥7% in body weight for both male and female. Participants were to wear the same type of clothes at each measurement, preferably a gown and no shoes. All body weight measurements were to have been taken post-void.
Measured: Baseline to Post-Week 214 follow-up visit
Secondary outcomes (11)
Mean Change From Baseline in Serum Sodium Measurements
Sodium measurements obtained at designated intervals were compared to each participant's Baseline sodium level at the beginning of placebo-controlled therapy in their original trial and from Baseline on initiation of therapy in the open-label trial.
Measured: Baseline of parent trial to Week 214
Change From Baseline in Percentage of Participants With Severe Hyponatremia
Percentage of participants with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at Baseline and each study visit.
Measured: Baseline to Week 214
Change From Baseline in Percentage of Participants With Mild Hyponatremia
Percentage of participants with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at Baseline and each study visit.
Measured: Baseline to Week 214
Change From Baseline in Percentage of Participants With Normal Sodium Levels
Percentage of participants with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at Baseline and each study visit.
Measured: Baseline to Week 214
Percentage of Participants Requiring Prescription of Fluid Restriction
Percentage of participants requiring prescription of fluid restriction for the express purpose of treating hyponatremia during each period of the trial. Assessed descriptively at each visit.
Measured: Baseline to Post-Week 214 follow-up visit
Number of Participants Requiring Prescription of Hypertonic Saline
Percentage of participants requiring prescription of hypertonic saline for the express purpose of treating hyponatremia during each period of the trial, assessed descriptively at each visit.
Measured: Baseline to Post-Week 214 follow-up visit
Percentage of Participants Requiring Prescription of Other Medicines
Percentage of participants requiring prescription of other medicines for the express purpose of treating hyponatremia during each period of the trial, assessed descriptively at each visit.
Measured: Baseline to Post-Week 214 follow-up visit
Mean Change From Baseline in Body Weight by Visit for Those Participants Who Had Clinical Evidence of Hypervolemia at Baseline
Body weight at each visit (assessed only for those with clinical evidence of hypervolemia at Baseline) and was summarized using descriptive statistics.
Measured: Baseline to Week 214
Mean Change From Baseline in SF-12 (Health Survey) Physical Component Summary (PCS)
The PCS assess the physical and mental dimensions of health-related quality of life. The PCS is equal to the sum of the items of endurance activities, strength activities, gross coordination activities, and fine coordination activities. The PCS is a computed score with weighted function based on the 12 questions from the 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health) of the SF-12v1 questionnaire per instructions by the scale's publisher. The scale ranges from 0 to 100 with 0 representing the lowest level of health and 100 indicating the highest level of health.
Measured: Baseline to Week 214
Mean Change From Baseline in SF-12 (Health Survey) Mental Component Summary (MCS)
The MCS assess the physical and mental dimensions of health-related quality of life. The MCS is equal to the sum of the items of concentration activities, calculating activities, language activities, and memory activities. The MCS is a computed score with weighted function based on the 12 questions from the 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health) of the SF-12v1 questionnaire per instructions by the scale's publisher. The scale ranges from 0 to 100 with 0 representing the lowest level of health and 100 indicating the highest level of health.
Measured: Baseline to Week 214
Change From Baseline in the Hyponatremia Disease-specific Survey
Analysis of individual items of Hyponatremia Disease-specific Survey was not conducted, because the analysis of Hyponatremia Disease-specific Survey was focused on the PCS and MCS summary scores since these 2 scores were developed. Subgroup analyses of Hyponatremia Disease-specific Survey were also not conducted.
Measured: Baseline to Week 214
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2015 (estimated)
- Study startMay 2004
- Primary completionOct 2009
- Study completionOct 2009
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.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02449044
- Sponsor's protocol ID
- 156-03-244
- Status last verified
- Dec 2015
- First submitted
- 14 May 2015
- Last updated
- 21 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Berl T, Quittnat-Pelletier F, Verbalis JG, Schrier RW, Bichet DG, Ouyang J, Czerwiec FS; SALTWATER Investigators. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr;21(4):705-12. doi: 10.1681/ASN.2009080857. Epub 2010 Feb 25.
PubMed 20185637
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International, Multicenter, Study of One-year, Open-label, Titrated Oral Tolvaptan Tablet Administration in Patients With Chronic Hyponatremia: Extension to Studies 156-02-235 and 156-03-238 to Assess One-year Safety
- ClinicalTrials.gov ID
- NCT02449044
- Acronym / sponsor ID
- 156-03-244
- Conditions
- Hyponatremia
- Keywords
- Hyponatremia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2004
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 20 May 2015 (estimated)
- Results
- Posted 21 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety of long-term tolvaptan use in patients previously enrolled in shorter-term Phase 3 studies and gather information on the natural history of hyponatremia in the context of tolvaptan therapy and underlying disease states.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Experimental | Drug: TolvaptanEnrolled subjects began treatment with 15 mg tolvaptan QD. A titration between target doses of 15 mg, 30 mg, or 60 mg of trial medication was based on the subject's change in serum sodium concentration and clinical tolerance of the trial medication. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age greater than or equal to 18 years.
- Ability to provide informed consent or assent.
- Prior successful participation in a tolvaptan hyponatremia trial termination with evidence of continued need or desire for therapy.
Key exclusion criteria (5 listed)
- A current medical condition where long-term treatment with an aquaretic agent may present an undue risk to the patient.
- Hyponatremia which is acute, reversible, artifactual or due to conditions not associated with vasopressin excess or likely to respond to aquaretic therapy.
- Hyponatremia due to reversible medical condition or therapy
- Conditions associated with an independent imminent risk of morbidity and mortality
- Conditions which confound the assessment of endpoints.
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 |
|---|---|---|
| TolvaptanOnce Daily | Drug | Tolvaptan |
Primary outcome
Participants With Adverse Events (AEs)
Time frame: Baseline to Post-Week 214 follow-up visit
A TEAE was an AE that began after the first injection or was continuous from Baseline and was defined as any new medical problem, or exacerbation of an existing problem, whether or not it was considered drug-related by the study physician. An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-subject hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent the outcomes mentioned above.
Participants With Laboratory Values Abnormalities Reported as TEAEs
Time frame: Baseline to Post-Week 214 follow-up visit
The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria. Any value outside the normal range was flagged for the attention of the study physician who was to indicate whether the value was clinically significant for identifying laboratory values of potential clinical relevance. Participants noted with abnormal laboratory values are reported below.
Participants With Electrocardiogram (ECG) Related Abnormalities Reported as TEAEs
Time frame: Baseline to Post-Week 214 follow-up visit
The ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in HR outliers, PR outliers, QRS outliers, QT, QTcB, QTcF that were identified based on pre-defined criteria. Some of the pre-defined criteria for identifying ECG measurements of potential clinical relevance included: For QTcB and QTcF: baseline mean of QTcB and QTcF interval was new onset >500 msec, 30 - 60 msec, >60 msec; For QT: new onset >500 msec; For QRS outliers: >=25% change from baseline when QRS >100 msec; PR outliers: >=25% change from baseline when PR>200 msec; HR outliers: 25% decrease from baseline and HR <50 bpm or 25% increase from baseline and HR >100 bpm. New onset (>500 msec) in QT, QTcB, or QTcF means a participant who attained a value >500 msec during treatment period but not at each baseline visit. The ECG-related abnormalities are reported as TEAEs are mentioned below.
Participants With Vital Signs Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Time frame: Baseline to Post-Week 214 follow-up visit
The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria. Criteria for identifying vital signs of potential clinical relevance included: Heart rate, supine: >= 120 beats per minute (bpm) + increase of ≥15 bpm from Baseline and <=50 bpm + decrease of >= 15 bpm; Diastolic Blood Pressure, Supine: >=105 mmHg + increase of >=15 mmHg and <=50 mmHg + decrease of >=15 mmHg; Systolic Blood Pressure, Supine: >=180 mmHg + increase of >=20 mmHg and <= 90 mmHg + decrease of >=20 mmHg; Temperature (degree C): Increase of >=1.1 to >=38.3C. The vital sign abnormalities were reported as TEAEs are mentioned below.
Participants With Body Weight Abnormalities Reported as TEAEs
Time frame: Baseline to Post-Week 214 follow-up visit
The body weight evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Every effort was made to ensure that body weight measurements were performed in a reproducible and consistent manner. The pre-defined criteria was change of ≥7% in body weight for both male and female. Participants were to wear the same type of clothes at each measurement, preferably a gown and no shoes. All body weight measurements were to have been taken post-void.
11 secondary outcomes
Mean Change From Baseline in Serum Sodium Measurements
Time frame: Baseline of parent trial to Week 214
Change From Baseline in Percentage of Participants With Severe Hyponatremia
Time frame: Baseline to Week 214
Change From Baseline in Percentage of Participants With Mild Hyponatremia
Time frame: Baseline to Week 214
Change From Baseline in Percentage of Participants With Normal Sodium Levels
Time frame: Baseline to Week 214
Percentage of Participants Requiring Prescription of Fluid Restriction
Time frame: Baseline to Post-Week 214 follow-up visit
Number of Participants Requiring Prescription of Hypertonic Saline
Time frame: Baseline to Post-Week 214 follow-up visit
Percentage of Participants Requiring Prescription of Other Medicines
Time frame: Baseline to Post-Week 214 follow-up visit
Mean Change From Baseline in Body Weight by Visit for Those Participants Who Had Clinical Evidence of Hypervolemia at Baseline
Time frame: Baseline to Week 214
Mean Change From Baseline in SF-12 (Health Survey) Physical Component Summary (PCS)
Time frame: Baseline to Week 214
Mean Change From Baseline in SF-12 (Health Survey) Mental Component Summary (MCS)
Time frame: Baseline to Week 214
Change From Baseline in the Hyponatremia Disease-specific Survey
Time frame: Baseline to Week 214
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20185637Berl T, Quittnat-Pelletier F, Verbalis JG, Schrier RW, Bichet DG, Ouyang J, Czerwiec FS; SALTWATER Investigators. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr;21(4):705-12. doi: 10.1681/ASN.2009080857. Epub 2010 Feb 25.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tolvaptan in people with Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc..
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 5 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 21 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 Jan 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?
Participants With Adverse Events (AEs) (time frame: Baseline to Post-Week 214 follow-up visit). The study lists 5 primary outcomes in all. 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 NCT02449044, 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 21 Jan 2016.