Clinical Trial: Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase 3b, Multicenter, Randomized, Single-blind, Parallel Group Trial of the Effects of Titrated Oral SAMSCA(r) (Tolvaptan) 15, 30, or 60 mg QD Compared to Placebo Plus Fluid Restriction on Length of

Brief Summary: The purpose of this study is to determine if hospitalized patients with symptomatic hyponatremia treated with tolvaptan are in the hospital for less time than patients treated with fluid restriction. The study will also test if tolvaptan is better than fluid restriction in treating the symptoms of hyponatremia in hospitalized patients.

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

Current Primary Outcome: Length of Hospital Stay (LoS) [ Time Frame: 45 days ]

Original Primary Outcome: Compare treatment with tolvaptan without fluid restriction to placebo with fluid restriction [ Time Frame: 14 days ]

Current Secondary Outcome:

• Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms. [ Time Frame: Baseline to 48 hours post dose ]

  Change from baseline in blinded rater assessed CGI-S at 48 hours post-first dose or at discharge/rescue therapy, if earlier was assessed.

  The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.

• Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms. [ Time Frame: Baseline to 24 and 72 hours post dose ]

  Change in CGI-S of hyponatremia symptoms from pretreatment baseline at 24 and 72 hours post-first dose, or at discharge/rescue therapy if earlier was assessed.

  The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.

• Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms. [ Time Frame: Baseline to 48 hours post dose ]

  Change in CGI-I score at 48 hours post-first dose or discharge/rescue therapy, if earlier was assessed.

  The CGI-I is a one-question rating scale where the participant is asked to rate total improvement whether or not, in their judgment, it is due entirely to trial treatment. Compared to his/her condition at admission to the trial, how much has he/she changed? 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse

• Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]). [ Time Frame: 0 to 72 hours ]

  Average 24 hour AUC of serum sodium concentration change from baseline, from Day 1 Hour 0 up to 72 hours post-first dose was assessed.

  A serum sodium sample was drawn at pre-treament and 8, 24, 48, and 72 hours post-first dose. Serum sodium was also assessed between 36 and 72 hours after the last dose.

  Analysis of AUC was for daily average AUC, hence the units or AUC are mEq/L/24 hours.

• Time to First 2-point Improvement in CGI-S Score. [ Time Frame: Up to 72 hours ]
  CGI-S data up to 72 hours were used to identify 2-point improvements. Please refer to outcome measure 2 for details on the scale. For the analysis of time to first 2-point improvement in CGI-S, CGI-S data up to Hour 72 were used to identify 2-point improvements. Data for participants who received rescue therapy were censored at the time of receiving rescue therapy. For participants who were discharged before Hour 72 without reaching 2-point improvement in CGI-S, data were censored at the time of discharge. Other participants who did not reach the 2-point improvement during the 72 hours also had their data censored at their last CGI-S observations within 72 hours.
• Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2. [ Time Frame: 48 hours post dose ]
  Percentage of responders (defined as CGI-I score of 1 = very much improved or 2 = much improved) at 48 hours post-first dose, or at discharge/rescue therapy, if earlier. Participants given rescue therapy were given a score of 7.
• Percentage of Participants Requiring Rescue Therapy for Hyponatremia [ Time Frame: 7 days ]
  Percentage of participants requiring rescue therapy within first 7 days of treatment for hyponatremia.

Original Secondary Outcome:

• Key secondary: Change in CGI-S of hyponatremia symptoms from pretreatment baseline to 48 hours post first dose, or at discharge/rescue therapy if earlier [ Time Frame: 48 hours ]
• Change in CGI-S of hyponatremia symptoms from pretreatment baseline at 24 and 72 hours post first dose, or at discharge/rescue therapy if earlier [ Time Frame: 24 and 72 hours ]
• Clinical Global Impression - Improvement scale (CGI-I) score at 48 hours post first dose or discharge/rescue therapy, if earlier. [ Time Frame: 48 hours ]
• Percentage of subjects requiring rescue therapy for hyponatremia through Day 7 post first dose [ Time Frame: 7 days ]
• Time to 2-point improvement in CGI-S score [ Time Frame: 7 days ]
• Percentage of responders (CGI-I score of 1 = very much improved or 2 = much improved) at 48 hours post first dose or discharge/rescue therapy, if earlier [ Time Frame: 48 hours ]
• Descriptive summary statistics for standard safety assessments [ Time Frame: 24, 48, and 72 hours ]
  Adverse events, vital signs, laboratory tests, and physical examinations

Dates:
Date Received: October 22, 2010
Date Started: October 2010
Date Completion:
Last Updated: October 21, 2014
Last Verified: October 2014