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

Hyponatremia Clinical Trial

— SIADH Safety  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00264914
• Other study ID #: SFY5904
• Secondary ID: LTS10208EudraCT
• Status: Completed
• Phase: Phase 3
• First received: December 12, 2005
• Last updated: January 19, 2009
• Start date: July 2005
• Est. completion date: August 2007

Study information

• Verified date: January 2009
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 2007
• Est. primary completion date: August 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 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Insipidus
• Hyponatremia
• Inappropriate ADH Syndrome
• Syndrome

Intervention

Drug:
• SR121463B

Locations

Country	Name	City	State
Australia	Sanofi-Aventis Administrative Office	Macquarie Park
Belgium	Sanofi-Aventis Administrative Office	Diegem
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	sanofi-aventis Canada	Laval
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Berlin
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Hungary	Sanofi-Aventis Administrative Office	Budapest
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Switzerland	Sanofi-Aventis Administrative Office	Geneva
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  France,  Germany,  Hong Kong,  Hungary,  Russian Federation,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety : Physical examination, vital signs, adverse events, electrocardiogram, hematology, serum chemistry
Secondary	Serum sodium

External Links

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