Hypovolemic Hyponatremia
Conditions
Keywords
hyponatremia, Non-acute and non hypovolemic hyponatremia
Brief summary
This is a randomized, double-blind, multicenter, placebo-controlled (standard therapy + placebo), phase 2 efficacy and safety study of the Tolvaptan tablets in treatment of patients with non-hypovolemic non-acute hyponatremia arising from a variety of etiologies. 240 (120 in each group) patients are to be enrolled randomly into Tolvaptan group or placebo group. Subjects in Tolvaptan group will receive standard therapy + Tolvaptan (15-60mg/day), while those in control group receiving standard therapy + placebo. The starting dose of tolvaptan is 15mg and it could be titrated up to 30mg and then,if necessary, to the maximum of 60mg according to a certain titration scheme based on patients' response of serum sodium level. The study includes a 2-day screening period from day -2 to day -1, 7-day inpatient study treatment (day 1 to day 7 ). After study treatment, subjects will be Followed-up on safety events on day 14 - 16. The Primary Efficacy Variable is the change of serum sodium from baseline. For patients with Congestive Heart Failure (CHF) or hepatic cirrhosis, change of body weight, fluid balance and symptoms improvement of CHF and hepatic edema will be assessed as secondary efficacy variables.
Interventions
DRUGTolvaptan
Tablet;15mg/tab;15/30/60mg/day for 7days Plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.
DRUGPlacebo
placebo plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Otsuka Beijing Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent. 2. Age:18～75 (when informed consent is obtained)，male or female. 3. Non-hypovolemic and non acute hyponatremia with a Serum sodium \< 135mEq/L before randomization. (main underlying diseases include CHF, hepatic cirrhosis with edema, SIADH and others) 4. In-patient subjects.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change of average daily Area Under the Curve (AUC) of serum sodium by day 4 and 7 comparing with baseline serum sodium level within the double-blind therapy period. | 4 and 7 days |
Secondary
| Measure | Time frame |
|---|---|
| For CHF and hepatic edema patients, improvement of symptoms and relevant physical examination measures or ultrasound test findings . Other secondary efficacy variables on blood serum sodium, fluid balance or body weight change. | 4 or 7 days |
Countries
China
Outcome results
None listed