None listed
Conditions
Interventions
Intervention1: Lixivaptan: 25mg start dose
Control Intervention1: None: Not Applicable
Sponsors
CARDIOKINE
No Secondary Sponsor
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age greater than or equal to 18 years 2. Ability to provide informed consent or assent Note: Patients must have the ability to clearly indicate their own informed consent/ assent for participation in this study. Sole consent by legal guardian will not be considered acceptable; however, signature of the consent by a guardian on behalf of a consenting patient incapable of affixing his or her own signature may be acceptable (e.g., high spinal cord injury). Consent by a legal guardian on behalf of patients with diminished capacity (e.g., stable schizophrenia, encephalopathy or senile dementia) must be made with the patient?s assent and must comply with the requirements of the site?s Independent Ethics Committee (IEC) or Institutional Review Board (IRB). Special arrangements for such patient?s care and supervision must be outlined to the site?s IRB/IEC. Patients with evidence of significant neurological symptoms attributable to hyponatremia, should use standard therapies to correct the hyponatremia. This correction must at a minimum improve cognition to the point where a valid informed consent may be given and where the likelihood of seizures or other danger has been mitigated. 3. Prior participation in a lixivaptan hyponatremia trial with evidence of continued need or desire for therapy. Patients must have demonstrated acceptable study drug compliance ( >70% of prescribed drug taken) and adherence to study procedures in the parent trial. Patients may be eligible if after Principal Investigator (PI) consultation with the Medical Monitor they have been withdrawn from the previous study due to a perceived lack of treatment effect requiring the use of intravenous (IV) saline infusion or alternate excluded therapy. The patient?s therapeutic nonresponse should be appropriately documented. No effort to unblind the patient?s previous treatment assignment should be undertaken with the sole intent of determining whether a nonresponse resulted from the patient?s receiving placebo or to their condition?s resistance to lixivaptan. While the ?need for therapy? in mild hyponatremia (sodium >129 mEq/L [mmol/L]), or even in the lower ranges of normal (sodium 135 to140 mEq/L [mmol/L]) is not established, based on the PI?s and patient?s agreement as to therapy?s desirability, enrollment in this study is possible. Justification for enrollment of patients whose sodium at entry is in the normal range must be given to, and accepted by, the Medical Monitor for the study.
Exclusion criteria
Exclusion criteria: 1. A current medical condition where long-term treatment with an aquaretic agent may present an undue risk to the patient For example: a. Women who are pregnant, breast feeding, or of childbearing potential who are not using acceptable contraceptive methods. b. Conditions limiting access to water (e.g., bedridden and noncommunicative) c. Severely disordered thirst (e.g., psychogenic polydipsia, hydrophobia or anorexia) d. Patients with urinary outflow obstruction (hydronephrosis is a risk unless catheterized) e. Significant hypotension (systolic blood pressure 90 mmHg) or pulmonary artery hypertension (fragile intravascular fluid balance) f. Known allergy to any vasopressin antagonist or any condition for which treatment with a vasopressin antagonist may present undue risk to the patient. 2. Hyponatremia which is acute, reversible, artifactual or due to conditions not associated with vasopressin excess or likely to respond to aquaretic therapy. Note: By definition all patients entering in the preceding trials had chronic, non-reversible, nonartifactual hyponatremia. It is plausible that between the patient?s completion of these trials one or more of these factors may now exist. In such circumstances, the patient should not be enrolled. For example: a. Hyponatremia in hypovolemic states Hypovolemic hyponatremia is defined as the presence of clinical and historical evidence of extracellular fluid volume depletion. Examples of clinical hypovolemic hyponatremia states include conditions where restoration of plasma volume results in correction and maintenance of normal plasma sodium concentration or those associated with critically low central venous pressure (5 cm H2O) or pulmonary capillary wedge pressure (5 mmHg); but do not include conditions such as CHF or cirrhosis where there is evidence of fluid overload (e.g., ascites or dependent edema) despite an inappropriate homeostatic response to perceived intravascular volume depletion. b. Acute and transient Hyponatremia Associated with head/brain trauma or post-operative pain, acute water intoxication, polydipsia, intravenous (IV) fluid administration, isolated pulmonary infection c. Artifactual Hyponatremia As due to hyperglycemia or hyperlipidemia d. Hyponatremia in states of severe renal impairment (creatinine 3.0 mg/dL) 3. Hyponatremia due to reversible medical condition or therapy For example: a. Severe, uncontrolled hypothyroidism or uncontrolled hypoadrenalism. b. Use of a medication, known to be associated with hyponatremia, which may be safely and easily substituted for another class. 4. Conditions associated with an independent imminent risk of morbidity and mortality. Patients whose prognosis suggests a life expectancy of at least 6 months are eligible; however, if the prognosis suggests a significant likelihood of a morbid or mortal event within the expected duration of the study, this information should be collected at time of enrollment.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 1. To demonstrate that after 28 weeks of open-label lixivaptan treatment, improvements in the time to complete the Trail Making Test (Part B) [TMT-B] will be maintained compared to baseline 2. To demonstrate that after 28 weeks of open-label lixivaptan administration, improvements in the Medical Outcomes Survey (MOS-6) will be maintained compared to baseline Timepoint: Not Applicable | — |
Primary
| Measure | Time frame |
|---|---|
| Lixivaptan administration will maintain increased serum sodium concentration during the open label treatment period. 1. To assess the safety of long-term lixivaptan use in patients who were previously enrolled in one of the 3 Phase III trials. 2. To assess the effect of lixivaptan re-administration, and 3. To gather information on the natural history of hyponatremia in the context of Lixivaptan therapy and underlying disease states Timepoint: Not Applicable | — |
Countries
India
Contacts
Public ContactArati Patil
Senior Manager, Medical Affairs
Outcome results
None listed