156-12-203: Phase I Tolvaptan in subjects with SIADH (Hormone)
Research type
Research Study
Full title
156-12-203: A Phase 1b, Multicenter, Pilot, Randomized, Double-blind Trial to Determine the Pharmacokinetics and Pharmacodynamics of Orally Administered Tolvaptan 3.75, 7.5, and 15 mg Tablets in Subjects with Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion
IRAS ID
131822
Contact name
Pierre-Marc Bouloux
Contact email
Sponsor organisation
Otsuka Pharmaceutical Development and Commercialization
Eudract number
2013-000933-11
Research summary
This is a study of male and female patients older than 18 years with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and serum sodium concentration between 120 and 133mmol/L to determine the Pharmacokinetics (PK) (absorption and distribution of drug) and Pharmacodynamics (PD) (the effects of the drug on the body) of a single Tolvaptan tablet in 3 different doses.
Tolvaptan is approved in the EU for treatment of hyponatremia due to SIADH. Patients with hyponatremia have low amount of sodium (salt) in the blood. In SIADH the body produces large amounts of antidiuretic hormone which leads to water excess and low blood sodium concentration.
Treatment starts at 15 mg. Increasingly, usage in Europe start at 7.5 mg as Physicians believe this dose is effective and causes less chance of blood sodium levels to be corrected too fast. When low blood sodium levels are corrected too quickly, there is a risk of neurological damage to the patient. Therefore there is a need to study if usage of lower doses could minimise the risk of rapid overcorrection of blood sodium levels.
Thirty patients will randomly be assigned to take one of three orally administered 3.75mg, 7.5mg or 15mg Tolvaptan tablets once. The study is double-blind meaning patients and study team will not know which dose they are taking unless there is an emergency. The study will last up to 29 days per patient.
The main aims of this study are to find out the greatest change in the sodium levels after each dose of the medication and how long it takes for the greatest change to take place. The secondary aim is to find out the PK and the time course of changes in urine volume and fluid balance after each dose.
Research is funded by Otsuka Pharmaceutical Development & Commercialization, Inc.
REC name
London - City & East Research Ethics Committee
REC reference
13/LO/1245
Date of REC Opinion
29 Oct 2013
REC opinion
Further Information Favourable Opinion