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

Hyponatremia Clinical Trial

— SIADH  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00264927
• Other study ID #: EFC4489
• Status: Completed
• Phase: Phase 3
• First received: December 12, 2005
• Last updated: December 9, 2008
• Start date: May 2004
• Est. completion date: September 2007

Study information

• Verified date: December 2008
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Insipidus
• Hyponatremia
• Inappropriate ADH Syndrome
• Syndrome

Intervention

Drug:
• SR121463B

Locations

Country	Name	City	State
Belgium	Sanofi-Aventis Administrative Office	Diegem
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	Sanofi-Aventis Administrative Office	Laval
Croatia	Sanofi-Aventis Administrative Office	Zagreb
Germany	Sanofi-Aventis Administrative Office	Berlin
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Hungary	Sanofi-Aventis Administrative Office	Budapest
Netherlands	Sanofi-Aventis Administrative Office	Gouda
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Spain	Sanofi-Aventis Administrative Office	Barcelona
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Croatia,  Germany,  Hong Kong,  Hungary,  Netherlands,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum sodium
Secondary	Urinary and serum osmolality, free water clearance, urinary volume, urinary electrolytes, weight, thirst,
Secondary	Safety: Physical examination, vital signs, adverse events, ECG, hematology, serum chemistry

External Links

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