Phase 3
N=57
Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients
Hyponatremia
Bottom Line
View on ClinicalTrials.gov: NCT00550459 ↗Enrolled (actual)
57
Serious AEs
5.3%
Results posted
Apr 2011
Primary outcome: Primary: Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores) — 0.20; 0.39 Z-score — p=0.08
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tolvaptan (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- Primary completion
- Feb 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores) |
0.20; 0.39 | 0.08 |
| SECONDARY Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests |
0.21; 0.33 | 0.21 |
| SECONDARY Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test |
0.04; 0.31 | 0.02 sig |
| SECONDARY 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 |
0.24; 0.48 | 0.21 |
| SECONDARY Change From Baseline in Overall Neurocognitive Composite Score |
0.19; 0.30 | 0.16 |
| SECONDARY Change From Baseline in Gait Test (Timed Get-Up-and-Go Test) |
1.06; -0.43 | 0.23 |
| SECONDARY Change From Baseline in Postural Stability Test |
1.3; -0.35 | 0.18 |
| SECONDARY Change From Baseline in Serum Sodium; ITT Population |
2.23; 7.04 | <0.0001 sig |
| SECONDARY Number of Patients With Vital Sign Abnormalities: Blood Pressure |
2; 0 | — |
| SECONDARY Number of Patients With Vital Sign Abnormalities: Pulse Rate |
0; 0 | — |
| SECONDARY Number of Patients With Vital Sign Abnormalities: Body Weight |
1; 1 | — |
| SECONDARY Number of Patients With Vital Sign Abnormalities: Body Temperature |
1; 0 | — |
| SECONDARY Number of Patients With Hematology Laboratory Abnormalities: Hemoglobin |
0; 1 | — |
| SECONDARY Number of Patients With Hematology Laboratory Abnormalities: Activated Partial Thromboplastin Time (aPTT) |
1; 3 | — |
| SECONDARY Number of Patients With Hematology Laboratory Abnormalities: Lymphocytes |
1; 2 | — |
| SECONDARY Number of Patients With Hematology Laboratory Abnormalities: Neutrophils |
2; 0 | — |
| SECONDARY Number of Patients With Serum Chemistry Laboratory Abnormalities: Blood Urea Nitrogen (BUN) |
1; 2 | — |
| SECONDARY Number of Patients With Serum Chemistry Laboratory Abnormalities: Uric Acid |
0; 1 | — |
| SECONDARY Number of Patients With Serum Chemistry Laboratory Abnormalities: Cholesterol |
0; 2 | — |
| SECONDARY Number of Patients With Serum Chemistry Laboratory Abnormalities: Glucose |
2; 0 | — |
| SECONDARY Number of Patients With Serum Chemistry Laboratory Abnormalities: Magnesium |
0; 1 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: QT >500 Milliseconds (Msec) |
1; 0 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: QRS Interval |
1; 1 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec |
3; 4 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec |
2; 3 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: ST Segment |
0; 2 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave |
1; 1 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI) |
0; 1 | — |
| SECONDARY Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia |
2; 6 | — |
Summary
Demonstrate an improvement in the composite scores of validated neurocognitive tests in elderly subjects with chronic sub-clinical (i.e., asymptomatic) hyponatremia.
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.
Data sourced from ClinicalTrials.gov (NCT00550459). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.