International, Multicenter, Study of One-year, Open-label, Titrated Oral Tolvaptan Tablet Administration in Patients With Chronic Hyponatremia

December 15, 2015 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
111

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age greater than or equal to 18 years.
  2. Ability to provide informed consent or assent.
  3. Prior successful participation in a tolvaptan hyponatremia trial termination with evidence of continued need or desire for therapy.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tolvaptan
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.
Drug: Tolvaptan
Once Daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline to Post-Week 214 follow-up visit
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.
Baseline to Post-Week 214 follow-up visit
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.
Baseline to Post-Week 214 follow-up visit
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.
Baseline to Post-Week 214 follow-up visit
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.
Baseline to Post-Week 214 follow-up visit

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Serum Sodium Measurements
Time Frame: Baseline of parent trial to Week 214
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.
Baseline of parent trial to Week 214
Change From Baseline in Percentage of Participants With Severe Hyponatremia
Time Frame: Baseline to Week 214
Percentage of participants with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at Baseline and each study visit.
Baseline to Week 214
Change From Baseline in Percentage of Participants With Mild Hyponatremia
Time Frame: Baseline to Week 214
Percentage of participants with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at Baseline and each study visit.
Baseline to Week 214
Change From Baseline in Percentage of Participants With Normal Sodium Levels
Time Frame: Baseline to Week 214
Percentage of participants with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at Baseline and each study visit.
Baseline to Week 214
Percentage of Participants Requiring Prescription of Fluid Restriction
Time Frame: Baseline to Post-Week 214 follow-up visit
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.
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 hypertonic saline for the express purpose of treating hyponatremia during each period of the trial, assessed descriptively at each visit.
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
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.
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
Body weight at each visit (assessed only for those with clinical evidence of hypervolemia at Baseline) and was summarized using descriptive statistics.
Baseline to Week 214
Mean Change From Baseline in SF-12 (Health Survey) Physical Component Summary (PCS)
Time Frame: Baseline to Week 214
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.
Baseline to Week 214
Mean Change From Baseline in SF-12 (Health Survey) Mental Component Summary (MCS)
Time Frame: Baseline to Week 214
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.
Baseline to Week 214
Change From Baseline in the Hyponatremia Disease-specific Survey
Time Frame: Baseline to Week 214
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.
Baseline to Week 214

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 14, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 20, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 21, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 15, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 156-03-244

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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