Clinical trial NCT00264927: Efficacy and Safety of SR121463B in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion
Official title: A Randomized, Double-Blind, Placebo-Group, Multicenter Study Evaluating the Efficacy and Safety 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: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy of SR121463B in correcting hyponatremia 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. To assess the safety and tolerability of SR121463B in patients with SIADH.

The double blind period is followed by 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 nay 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, ALT and /or AST \>2x upper limit of normal
* QTcB \> 500 ms
* Serum potassium \> 5 mmol/L

Primary outcomes:
measure: Serum sodium
Secondary outcomes:
measure: Urinary and serum osmolality, free water clearance, urinary volume, urinary electrolytes, weight, thirst,
measure: Safety: Physical examination, vital signs, adverse events, ECG, hematology, serum chemistry
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
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 Administrative Office
city: Zagreb
country: Croatia
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: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD CSD
role: STUDY_DIRECTOR
References: