Clinical trial NCT00550459: Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients
Official title: A Pilot, Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of the Effects of Titrated Oral Tolvaptan 15, 30, or 60 mg QD on Cognitive and Neurological Function in Elderly Hyponatremic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyponatremia
Keywords: Hyponatremia
Cognitive
Neurological Function
Elderly
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Otsuka Pharmaceutical Co., Ltd.
First posted: 2007-10-29
Enrollment: 57
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Demonstrate an improvement in the composite scores of validated neurocognitive tests in elderly subjects with chronic sub-clinical (i.e., asymptomatic) hyponatremia.

Detailed description: Subjects will be randomized, with stratification by baseline sodium \<130 or ≥ 130 mEq/L\[mmol/L\] to receive either tolvaptan 15 mg tablet or matching placebo tablet at doses of 15, 30 or 60 mg for 21 days. During this period, fluid restrictions should be loosened or suspended, until the subject's response to therapy can be evaluated, typically over the first few days of therapy. Fluid restriction may be reinstituted at any time in subjects whose sodium fails to improve or worsens with study therapy. A forced-titration up to 60 mg of study drug by day 3 to 7 will be based on the subject's serum sodium Subjects entering the study with a serum sodium concentration less than 130 mEq/L\[mmol/L\] may be fluid restricted if necessary at the discretion of the Investigator. Subjects should be monitored closely during the first 24 hours of treatment for dosing titration. The total dosing duration will be up to 21 days (plus 3 day treatment window). Subjects will return to the clinic on Day 22 (+3 days) for assessments and will complete a follow-up visit on Day 28 (+2 days).

Eligibility criteria: Inclusion Criteria:

* Women and men 50 years of age or older.
* Serum Sodium ≥123 and ≤ 134 mEq/L \[mmol/L\]at screening and baseline.
* Subjects with serum sodium concentrations ≥118 and ≤122 mEq/L\[mmol/L\] at screening and baseline may be entered into the trial based on consultation and approval from the study medical monitor.

Exclusion Criteria:

* Conditions or history which may present a safety concern to the subject or their offspring or extreme susceptibility to hypotension with sudden fluid loss (aquaresis).
* Hyponatremia that is acute, easily reversible, artifactual, or due to a condition not associated with vasopressin excess or likely to respond to aquaretic therapy.
* Conditions associated with an independent imminent risk of morbidity and mortality.
* Conditions which may confound the assessment of endpoints, history of poor compliance, participation in a clinical trial believed by the PI or Sponsor likely to confound endpoint assessments.
* Conditions which may confound primary endpoints of cognitive function.

Primary outcomes:
measure: Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)
timeFrame: baseline and Day 22
Secondary outcomes:
measure: Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests
timeFrame: baseline and Day 22
measure: Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test
timeFrame: baseline and Day 22
measure: Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Processing Speed of Rapid Visual Information Processing Test, Numeric Working Memory Test, and Word Recognition Test
timeFrame: baseline and Day 22
measure: Change From Baseline in Overall Neurocognitive Composite Score
timeFrame: baseline and Day 22
measure: Change From Baseline in Gait Test (Timed Get-Up-and-Go Test)
timeFrame: baseline and Day 22
measure: Change From Baseline in Postural Stability Test
timeFrame: baseline and Day 22
measure: Change From Baseline in Serum Sodium; ITT Population
timeFrame: Baseline and Day 22
measure: Number of Patients With Vital Sign Abnormalities: Blood Pressure
timeFrame: 28 days
measure: Number of Patients With Vital Sign Abnormalities: Pulse Rate
timeFrame: 28 days
measure: Number of Patients With Vital Sign Abnormalities: Body Weight
timeFrame: 28 days
measure: Number of Patients With Vital Sign Abnormalities: Body Temperature
timeFrame: 28 days
measure: Number of Patients With Hematology Laboratory Abnormalities: Hemoglobin
timeFrame: 28 days
measure: Number of Patients With Hematology Laboratory Abnormalities: Activated Partial Thromboplastin Time (aPTT)
timeFrame: 28 days
measure: Number of Patients With Hematology Laboratory Abnormalities: Lymphocytes
timeFrame: 28 days
measure: Number of Patients With Hematology Laboratory Abnormalities: Neutrophils
timeFrame: 28 days
measure: Number of Patients With Serum Chemistry Laboratory Abnormalities: Blood Urea Nitrogen (BUN)
timeFrame: 28 days
measure: Number of Patients With Serum Chemistry Laboratory Abnormalities: Uric Acid
timeFrame: 28 days
measure: Number of Patients With Serum Chemistry Laboratory Abnormalities: Cholesterol
timeFrame: 28 days
measure: Number of Patients With Serum Chemistry Laboratory Abnormalities: Glucose
timeFrame: 28 days
measure: Number of Patients With Serum Chemistry Laboratory Abnormalities: Magnesium
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: QT >500 Milliseconds (Msec)
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: QRS Interval
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: ST Segment
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)
timeFrame: 28 days
measure: Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia
timeFrame: 28 days
Other outcomes:
Locations:
city: Hawthorne
country: United States
facility: Sarah. S. Olelewe, MD
state: California
city: Vista
country: United States
facility: Progressive Clinical Research
state: California
city: Colorado Springs
country: United States
facility: Pikes Peak Cardiology
state: Colorado
city: Largo
country: United States
facility: Innovative Research of West FL
state: Florida
city: Punta Gorda
country: United States
facility: Coastal Nephrology Assoc. Research Center
state: Florida
city: Conyers
country: United States
facility: Rockdale Medical Research Associates
state: Georgia
city: Natchitoches
country: United States
facility: Otis Barnum, DO
state: Louisiana
city: Fargo
country: United States
facility: Lillestol Research, LLC
state: North Dakota
city: Columbia
country: United States
facility: Carolina Research Associates
state: South Carolina
city: Lebanon
country: United States
facility: Wayne O. Wells, MD
state: Tennessee
city: Houston
country: United States
facility: Memorial Clinical Associates
state: Texas
city: Charlottesville
country: United States
facility: Mitchell Rosner, MD
state: Virginia
Study officials:
affiliation: Georgetown University, Washington, DC, 20007 USA
name: Joseph Verbalis, MD
role: PRINCIPAL_INVESTIGATOR
References: