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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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.

Detailed Summary:
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Current 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 E

    Original Primary Outcome:

    • Subjects with changes in vital signs reported as Treatment Emergent Adverse Events [ Time Frame: baseline, Day1, Day14, Day 31, Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106, 118, 130, 142, 154, 166, 178, 190, 202, 214, and Follow-Up Visit ]
    • Subjects with changes in electrocardiogram results reported as Treatment Emergent Adverse Events [ Time Frame: baseline, post-dose 8 hours, Day 1, Day14, Weeks 58, 106, 154, 214/ET and at the Follow-up visit ]
    • Subjects with changes in laboratory values reported as Treatment Emergent Adverse Events [ Time Frame: baseline, post-dose 8 hours, Day 1, Day 14, Weeks 58, 106, 154, 214/ET and at the Follow-up visit ]
    • Adverse events (AEs) [ Time Frame: baseline, Day 1, Day 14, Day 31, Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106, 118, 130, 142, 154, 166, 178, 190, 202, 214, and Follow-Up Visit ]
    • Subjects with changes in body weight reported as Treatment Emergent Adverse Events [ Time Frame: baseline, Day 1, Day 14, Day 31, Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106, 118, 130, 142, 154, 166, 178, 190, 202, 214, and Follow-Up Visit ]


    Current Secondary Outcome:

    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.
    • 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.


    Original Secondary Outcome:

    • Percentage of Patients with Severe Hyponatremia [ Time Frame: Baseline, Day 2, Day 14, Day 21 and Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106,118, 130, 142, 154, 166, 178, 190, 202, and 214 ]
      Percentage of patients with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at baseline and each study visit.
    • Percentage of Patients with Mild Hyponatremia [ Time Frame: Baseline, Day 2, Day 14, Day 21 and Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106,118, 130, 142, 154, 166, 178, 190, 202, and 214 ]
      Percentage of patients with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at baseline and each study visit.
    • Percentage of Patients with Normal Hyponatremia [ Time Frame: Baseline, Day 2, Day 14, Day 21 and Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106,118, 130, 142, 154, 166, 178, 190, 202, and 214 ]
      Percentage of patients with varying degrees of hyponatremia ("severe" <130, "mild" 130-135, "normal" >135 mEq/L) at baseline and each study visit.
    • Percentage of patients requiring prescription of fluid restriction [ Time Frame: Baseline, Day 2, Day 14, Day 21 and Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106,118, 130, 142, 154, 166, 178, 190, 202, and 214 ]
      Percentage of patients requiring prescription of fluid restriction for the express purpose of treating hyponatremia during each period of the trial. Assessed descriptively at each visit.
    • Percentage of patients requiring prescription of hypertonic saline [ Time Frame: Baseline, Day 2, Day 14, Day 21 and Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106,118, 130, 142, 154, 166, 178, 190, 202, and 214 ]
      Percentage of patients requiring prescription of hypertonic saline for the express purpose of treating hyponatremia during each period of the trial. Assessed descriptively at each visit.
    • Percentage of patients requiring prescription of other medicines for Hyponatremia [ Time Frame: Baseline, Day 2, Day 14, Day 21 and Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106,118, 130, 142, 154, 166, 178, 190, 202, and 214 ]
      Percentage of patients requiring prescription of other medicines for the express purpose of treating hyponatremia during each period of the trial. Assessed descriptively at each visit.
    • SF-12 (health survey)Physical Component Summary (PCS) [ Time Frame: baseline, Day 31, and Weeks 26, 34, 42, 50, 58, 70, 82, 94, 106 and Week 214/ET ]
      Change from baseline in the SF-12 (health survey) Physical Component Summary (PCS)
    • SF-12 (health survey)Mental Component Summary (MCS) scales [ Time Frame: baseline, Day 31, and Weeks 26, 34, 42, 50, 58, 70, 82, 94, 106 and Week 214/ET ]
      Change from baseline in the SF-12 (health survey) Mental Component Summary (MCS) scales
    • Hyponatremia-specific patient and investigator questionnaire change from baseline [ Time Frame: Day 31, Weeks 26, 34, 42, 50, 58, 70, 82, 94, 106 and 214/ET ]
    • Subjects with changes in Sodium Measurements reported as Treatment Emergent Adverse Events [ Time Frame: Baseline Original Trial, Baseline Open Label, post-dose 8 hours, baseline, Day 1, Day 14, Day 31, Weeks 10, 18, 26, 34, 42, 50, 58, 70, 82, 94, 106, 118, 130, 142, 154, 166, 178, 190, 202, 214, and Follow-Up Visit ]
      Sodium measurements obtained at designated intervals will be compared to each patient'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.


    Information By: Otsuka Pharmaceutical Development & Commercialization, Inc.

    Dates:
    Date Received: May 14, 2015
    Date Started: May 2004
    Date Completion:
    Last Updated: December 15, 2015
    Last Verified: December 2015