A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Oral Lixivaptan Capsules in Subjects With Euvolemic Hyponatremia

Phase 3

Completed

• Conditions: Euvolemic Hyponatremia
• Interventions: Drug: Placebo; Drug: Lixivaptan

• Registration Number: NCT00876798
• Lead Sponsor: CardioKine Inc.

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of oral lixivaptan capsules in subjects with Euvolemic Hyponatremia.

Detailed Description

Phase I and Phase II clinical trials have demonstrated that lixivaptan may play an important role in treating hyponatremia and the signs and symptoms of water retention associated with HF, LCWA, and SIADH. Lixivaptan was previously evaluated in disease states characterized by hyponatremia with euvolemia (SIADH) and hyponatremia combined with fluid overload (HF, LCWA). Lixivaptan demonstrated correction in serum sodium concentration together with marked aquaresis in subjects with hyponatremia.

Study Timeline

• Study First Submitted: 2009-04-06
• Study First Submitted QC: 2009-04-06
• Study First Posted: 2009-04-07
• Study Start: 2009-06
• Status Verified: 2010-11
• Primary Completion: 2010-11
• Disposition First Submitted: 2011-06-20
• Disposition First Submitted QC: 2011-06-20
• Last Update Submitted: 2011-06-20
• Disposition First Posted: 2011-06-28
• Last Update Posted: 2011-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 206

Inclusion Criteria

1. Written informed consent.
2. Men or women aged 18 or older.
3. Diagnosis of euvolemic hyponatremia (Na+ < 135 mEq/L).
4. Willing to be observed in a monitored setting for approximately the first 8 hours following treatment initiation (first dose).
5. In the Investigator's judgement the patient has adequate visual and auditory acuity to allow participation in the trial.

Exclusion Criteria

1. Pregnant or breast-feeding women, or women planning to become pregnant or to breastfeed.
2. Overt symptoms of hyponatremia requiring immediate medical intervention (e.g., coma, seizures).
3. Acute or transient hyponatremia (e.g., associated with head trauma, postoperative state, or use of radiotherapy and/or chemotherapy).
4. Hyponatremia in hypovolemic states (e.g., due to fluid loss through vomiting, diarrhea, burns, etc.). Hypovolemic hyponatremia is defined as the presence of clinical evidence of extracellular fluid volume depletion.
5. Hyponatremia in hypervolemic states (e.g., congestive heart failure). Hypervolemia is defined as a presence of increased total body water with signs of edema.
6. Pseudohyponatremia (i.e., hyponatremia resulting from a laboratory artifact).
7. Hypertonic hyponatremia (e.g., hyponatremia in the setting of hyperglycemia).
8. Hyponatremia as a result of any medication that can safely be withdrawn.
9. Hyponatremia due to hypothyroidism or adrenal insufficiency.
10. Current diagnosis of psychogenic polydipsia.
11. Receiving within 7 days of enrollment other medication for treatment of hyponatremia, specifically: demeclocycline, lithium carbonate, urea, or any vasopressin antagonist.
12. Supine systolic arterial blood pressure of ≤ 90 millimeters of mercury (mmHg).
13. Serum creatinine > 3.0 mg/dL (> 265.2 mol/L).
14. Hypokalemia based on clinical sign/symptoms or lab findings (e.g., serum potassium < 3.5 mEq/L).
15. Uncontrolled diabetes mellitus as defined by the Investigators (e.g., hemoglobin - glycosylated [HbA1c] > 9%).
16. ST-segment elevation myocardial infarction (STEMI) within 30 days or active myocardial ischemia at the time of enrollment.
17. History of cerebral vascular accident (CVA) within 30 days prior to screening.
18. Severe malnutrition in the Investigator's judgment (e.g., body mass index [BMI] < 17).
19. Advanced liver disease or documented diagnosis of cirrhosis or alcoholic hepatitis.
20. Urinary tract obstruction (benign prostatic hypertrophy [BPH] allowed if non-obstructive).
21. History of chronic drug/medication abuse within the past 6 months or current alcohol abuse.
22. Terminally ill or moribund condition with little chance of short-term survival.
23. Receiving vasopressin or its analogs for treatment of any condition.
24. Known allergy to any vasopressin antagonist.
25. Previous participation in a lixivaptan study.
26. Recipient of any investigational treatment within 30 days prior to baseline visit.
27. Unable to take oral medications.
28. Significant neurological disorders (e.g., permanent neurological deficits, probable Alzheimer's disease, normal pressure hydrocephalus, Parkinsonian dementia complex, multi-infarct dementia, mixed dementia, or Huntington's disease).
29. Conditions limiting access to water or an inability to respond to thirst (e.g., hydrophobia, or non-communicative).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
1	Lixivaptan	Lixivaptan

Primary Outcome Measures

Name	Time	Method
To demonstrate that lixivaptan is safe and effective in achieving and maintaining increased serum sodium concentration in subjects with SIADH and other conditions of euvolemic hyponatremia.	6 months

Secondary Outcome Measures

Name	Time	Method
If lixivaptan demonstrates improvement in serum sodium, % of subjects achieving normalized serum sodium, % of subjects requiring fluid restriction, prevention of worsening hyponatremia, and the change from baseline to complete TMT-B.	6 months

Trial Locations

Locations (89)

Birmingham Nursing and Rehabilitation East; 🇺🇸 Birmingham, Alabama, United States

Healthscan Research, LLC; 🇺🇸 Montgomery, Alabama, United States

PsyPharma Clinical Research, Inc.; 🇺🇸 Phoenix, Arizona, United States

PsyPharma Clinical Research; 🇺🇸 Phoenix, Arizona, United States

Southern Arizona VA Health Care System (SAVAHCS); 🇺🇸 Tucson, Arizona, United States

Parkview Rehabilitation and Nursing; 🇺🇸 Little Rock, Arkansas, United States

Searcy Medical Center; 🇺🇸 Searcy, Arkansas, United States

AV Institute, Inc.; 🇺🇸 Carson, California, United States

Royal Care Nursing Home; 🇺🇸 Fountain Valley, California, United States

Sarah S. Olelewe, MD, Inc.; 🇺🇸 Hawthorne, California, United States

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