Clinical trial NCT00274326: DILIPO (DILutIonal HyPOnatremia)
Official title: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial Evaluating the Effect of a Vasopressin V2 Receptor Antagonist (SR121463B) on Serum Sodium in Patients With Dilutional Hyponatremia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congestive Heart Failure
Keywords: Hyponatremia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-01-10
Enrollment: 150
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: Primary:

* To assess the efficacy of SR121463B in correcting hyponatremia in patients with dilutional hyponatremia other than SIADH or cirrhosis

Secondary:

* To assess the long-term efficacy of SR121463B in maintaining normonatremia in these patients
* To assess the safety and tolerability of SR121463B

Detailed description: SR121463B is an orally effective non-peptide, potent, and highly selective V2 receptor antagonist causing free water elimination in animals and humans

Eligibility criteria: Inclusion Criteria:

* Male or Female patients aged 18 higher
* Dilutional Hyponatremia with serum sodium between 115 and 132 mmol/L
* Ability to give written informed consent (the informed consent may be signed by a legally authorized representative if the patient is unable to sign)

Exclusion Criteria:

* Presence of known or untreated adrenal insufficiency, SIADH or cirrhosis, or hyperthyroidism
* Presence of signs of hypovolemia
* Administration of other V2 receptor antagonists or demeclocycline or lithium within one month and urea within two days prior to study drug administration
* Presence of uncontrolled diabetes with fasting glycemia ³ 200 mg/dL (³ 11.09 mmol/L)
* Patients considered by the Investigator unsuitable candidates to receive an investigational drug (e.g., presence of any neurological symptoms that may worsen in five days, based on the judgment of the Investigator, or presence of any neurological symptoms for which the persistence of hyponatremia over several days may be deleterious)
* Administration of inducers of CYP3A4 (phenobarbital, phenytoin, rifampin, Saint John's Wort) or potent and moderate inhibitors of CYP3A4 within two weeks prior to study drug administration
* Presence or history of allergic reaction to SR121463B8
* Previous study with SR121463B
* Inadequate hematological, renal, and hepatic functions: hemoglobin (Hb) \< 9 g/dL, neutrophils \< 1,500/mm3, platelets \< 100,000/mm3, serum creatinine \> 175 mol/L (or clearance of creatinine \< 30 mL/min for sites where Ethics Committees require this parameter), serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2 x upper limit of normal (ULN)
* QTCB 500 ³ ms
* Positive pregnancy test and absence of medically approved contraceptive methods (e.g., surgical sterilization of more than one month duration, oral contraception or intrauterine device in combination with either diaphragm, condom, or spermicide) for females of childbearing potential
* Pregnancy or breast-feeding

Primary outcomes:
measure: EFFICACY:Serum Sodium
measure: SAFETY:Physical examination, vital signs, adverse events, electrocardiogram, hematology, serum chemistry
measure: PHARMACOKINETICS:Plasma SR121463B concentrations
Secondary outcomes:
measure: Weight; EQ-5D and pharmaco-economic assessments
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Macquarie Park
country: Australia
facility: sanofi-aventis Australia & New Zealand administrative office
state: New South Wales
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: Sanofi-Aventis Administrative Office
city: Athens
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Administrative Office
city: Midrand
country: South Africa
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Daniel Ter-Minassian, MD
role: STUDY_CHAIR
References:
citation: Aronson D, Verbalis JG, Mueller M, Krum H; DILIPO investigators. Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study. Eur J Heart Fail. 2011 Mar;13(3):327-36. doi: 10.1093/eurjhf/hfq226. Epub 2011 Jan 3.