Safety and Efficacy of SR121463B in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH Safety)

Sanofi

Status and phase

Completed

Phase 3

Conditions

Inappropriate ADH Syndrome

Hyponatremia

Treatments

Drug: SR121463B

Study type

Interventional

Funder types

Industry

Identifiers

NCT00264914

LTS10208

EudraCT : 2004-005239-35

SFY5904

Details and patient eligibility

About

To determine the long-term safety and tolerability of SR121463B in patients with syndrome of inappropriate antidiuretic secretion (SIADH). To assess the long-term efficacy of SR121463B in maintaining normal levels of serum sodium in patients with SIADH.

Long term safety is evaluated further in an open label extension study with flexible doses of satavaptan.

Enrollment

57 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female patients aged 18 years and higher.
SIADH (the diagnosis of SIADH is based on several criteria including true serum hypoosmolality, inappropriate urinary osmolality, clinical euvolemia, elevated urinary sodium excretion while on normal salt and water intake, and normal renal, adrenal, and thyroid functions: drug induced SIADH will be limited to carbamazepine or derivatives and antidepressants in patients in whom these drugs cannot be discontinued or easily replaced by other drugs)
Serum sodium between 115 and 132 mmol/L (at least two consecutive serum sodium levels of at least 24 hours apart, from Day -6 to Day -1); for sodium levels between 125 and 132 mmol/L, the spontaneous serum sodium increase between the two assessments on Day -1 should be < 4 mmol/L
Urinary osmolality >200mOsm/kg H2O
Urinary sodium > 30 mmol/L

Exclusion criteria

Patients with acute postoperative SIADH
Presence of dilutional hyponatremia in hypervolemic states such as congestive heart failure and liver disease with ascites
Presence of signs of hypovolemia (e.g., orthostatic hypotension, increased serum urea nitrogen, increased serum albumin, increased hematocrit, ...)
Administration of other V2 receptor antagonists or demeclocycline or lithium within one month, thiazides diuretics or spironolactone within 15 days, and urea or loop diuretics within two days prior to study drug administration
Patients with known treated or untreated adrenal deficiency
Presence of untreated hypothyroidism
Presence of uncontrolled diabetes with fasting glycemia > 200 mg/dL (> 11.09 mmol/L)
Presence of clinical and/or electrocardiographical signs of acute myocardial infarction or acute ischemia, or any other clinically significant abnormality according to the Investigator on a 12 lead ECG recording
Administration of inducers of CYP3A4 (phenytoin, rifampin, Saint John's Wort) or potent and moderate inhibitor so CYP3A4within two weeks prior to study drug administration
Inadequate hematological, renal and hepatic functions; hemoglobin (Hb) < 9 g/dL, neutrophils < 1,500/mm3, platelets <100,00/mm3, serum creatine >175 µmol/L (or clearance of creatine <30mL/min for where Ethics Committees require this parameter), ALT and /or AST >2x upper limit of normal
QTcB > 500 ms
Serum potassium > 5 mmol/L