Clinical trial NCT00264914: Safety and Efficacy of SR121463B in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion
Official title: An Open-Label, Multicenter Study Evaluating the Long-Term Safety and Efficacy of SR121463B in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Inappropriate ADH Syndrome
Hyponatremia
Keywords: Inappropriate ADH Syndrome
Hyponatremia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-12-13
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety : Physical examination, vital signs, adverse events, electrocardiogram, hematology, serum chemistry
Secondary outcomes:
measure: Serum sodium
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: sanofi-aventis Canada
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Causeway Bay
country: Hong Kong
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD CSD
role: STUDY_DIRECTOR
References: