Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients (INSIGHT)
26 de abril de 2011 actualizado por: Otsuka Pharmaceutical Development & Commercialization, Inc.
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
Demonstrate an improvement in the composite scores of validated neurocognitive tests in elderly subjects with chronic sub-clinical (i.e., asymptomatic) hyponatremia.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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).
Tipo de estudio
Intervencionista
Inscripción (Actual)
57
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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California
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Hawthorne, California, Estados Unidos, 90250
- Sarah. S. Olelewe, MD
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Vista, California, Estados Unidos, 92083
- Progressive Clinical Research
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Colorado
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Colorado Springs, Colorado, Estados Unidos, 80907
- Pikes Peak Cardiology
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Florida
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Largo, Florida, Estados Unidos, 33770
- Innovative Research of West FL
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Punta Gorda, Florida, Estados Unidos, 33950
- Coastal Nephrology Assoc. Research Center
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Georgia
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Conyers, Georgia, Estados Unidos, 30094
- Rockdale Medical Research Associates
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Louisiana
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Natchitoches, Louisiana, Estados Unidos, 71457
- Otis Barnum, DO
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North Dakota
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Fargo, North Dakota, Estados Unidos, 58106
- Lillestol Research, LLC
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South Carolina
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Columbia, South Carolina, Estados Unidos, 29201
- Carolina Research Associates
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Tennessee
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Lebanon, Tennessee, Estados Unidos, 37087
- Wayne O. Wells, MD
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Texas
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Houston, Texas, Estados Unidos, 77043
- Memorial Clinical Associates
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Virginia
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Charlottesville, Virginia, Estados Unidos, 22908
- Mitchell Rosner, MD
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
50 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador de placebos: 1
Placebo tablet given once a day for 21 days
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Placebo tablet given once daily for 21 days
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Comparador activo: 2
Tolvaptan 15 mg-60 mg tablet given once a day for 21 days.
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15-60 mg oral tablet given once a day for 21 days.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)
Periodo de tiempo: baseline and Day 22
|
Change from baseline to Day 22 in sum of all speed domain Z-scores:Reaction Time (Simple=recognize "yes" 50 times;Choice=recognize "yes" or "no" 50 times;Digit Vigilance=match 45 digits);Psychomotor Speed (Morse Tapping=tap button for 30 seconds with right & left hands);Processing Speed (Rapid Visual Information Processing=detect consecutive sequences of 3 odd or 3 even digits;Numeric Working Memory=recognize numbers from series of 5 digits among 30;Word Recognition=remember 15 prior learned words from 30 total;results age-matched to healthy controls from Cognitive Drug Research normative data
|
baseline and Day 22
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests
Periodo de tiempo: baseline and Day 22
|
Change from baseline in the individual neurocognitive domains Z-score for Reaction Time in Computer Tests (simple reaction time test, choice reaction time test, digit vigilance test); ITT population
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baseline and Day 22
|
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Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test
Periodo de tiempo: baseline and Day 22
|
Change from baseline to Day 22 in the individual neurocognitive domains Z-score for Psychomotor Speed (mean tap rate of Morse tapping test); ITT population
|
baseline and Day 22
|
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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
Periodo de tiempo: baseline and Day 22
|
Change from baseline to Day 22 in the individual neurocognitive domains Z-score for Processing Speed of Rapid Visual Information Processing Test, Numeric Working Memory Test, and Word Recognition Test; ITT population
|
baseline and Day 22
|
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Change From Baseline in Overall Neurocognitive Composite Score
Periodo de tiempo: baseline and Day 22
|
Change from Baseline to Day 22 in the overall Neurocognitive Composite Score (NCS)comprising the sum of 7 neurocognitive domain Z-scores (Reaction Time, Psychomotor Speed, Processing Speed, Continuity of Attention, Working Memory/Executive Functions, Quality of Episodic Verbal Memory, and Postural Stability); ITT population
|
baseline and Day 22
|
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Change From Baseline in Gait Test (Timed Get-Up-and-Go Test)
Periodo de tiempo: baseline and Day 22
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Change from baseline to Day 22 in Gait Test (Timed Get-Up-and-Go Test=time it takes for a seated subject to rise from a chair, walk 3 meters, walk around an object and return to sit in chair.
Values: under 10 sec (no difficulties), 10 to 20 sec (starting to have balance difficulty), over 30 sec (at high risk for falls and dependent in most activities of daily living and mobility); test assesses risk to elderly subjects of falling and higher scores in seconds indicate higher risk of falling; ITT population
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baseline and Day 22
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Change From Baseline in Postural Stability Test
Periodo de tiempo: baseline and Day 22
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Change from baseline to Day 22 in Postural Stability Test Z-score (This test measures gross motor control.
The ability to stand upright without moving is assessed using the SWAY meter that is modeled on the Wright Ataxiameter.
A cord from the meter is attached to the subject who is required to stand as still as possible with feet apart and eyes closed for 1 minute.
The test is then repeated with eyes open for 1 minute.
The outcomes of these tests are combined and measured as a movement Z-score.
Higher result=better postural stability); ITT population
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baseline and Day 22
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Change From Baseline in Serum Sodium; ITT Population
Periodo de tiempo: Baseline and Day 22
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Change from Baseline to Day 22 in Serum Sodium; ITT population
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Baseline and Day 22
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Number of Patients With Vital Sign Abnormalities: Blood Pressure
Periodo de tiempo: 28 days
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Incidence of abnormal systolic & diastolic blood pressure values post-baseline (abnormal systolic values: >=180 mmHg + increase of >=20 mmHg, <= 90 mmHg + decrease >=20 mmHg; abnormal diastolic values: >=105 mmHg+increase of >=15 mmHg, <=50 mmHg + decrease of >= 15 mmHg)
|
28 days
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Number of Patients With Vital Sign Abnormalities: Pulse Rate
Periodo de tiempo: 28 days
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Incidence of abnormal pulse rate post-baseline [abnormal values: >=120 beats per minute (bpm) + increase of >=15 bpm; <=50 bpm + decrease of >=15 bpm]
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28 days
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Number of Patients With Vital Sign Abnormalities: Body Weight
Periodo de tiempo: 28 days
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Incidence of clinically significant body weight change post-baseline (defined as change upward or downward of >=7%)
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28 days
|
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Number of Patients With Vital Sign Abnormalities: Body Temperature
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant changes in body temperature post-baseline (defined as an increase of >=1.1 to >=38.3 degrees Celsius)
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28 days
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Number of Patients With Hematology Laboratory Abnormalities: Hemoglobin
Periodo de tiempo: 28 days
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Incidence of clinically significant hemoglobin abnormalities post-baseline (normal range=11.8-16.8
g/dL)
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28 days
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Number of Patients With Hematology Laboratory Abnormalities: Activated Partial Thromboplastin Time (aPTT)
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant Activated Partial Thromboplastin Time (aPTT) levels post-baseline (normal range=22-34 seconds)
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28 days
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Number of Patients With Hematology Laboratory Abnormalities: Lymphocytes
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant lymphocyte count post-baseline (normal range = 16-46%)
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28 days
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Number of Patients With Hematology Laboratory Abnormalities: Neutrophils
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant neutrophil count post-baseline (normal range=1.8-8
thousands/microliter)
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28 days
|
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Number of Patients With Serum Chemistry Laboratory Abnormalities: Blood Urea Nitrogen (BUN)
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant BUN levels post-baseline (normal range=7-30 mg/dL)
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28 days
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Number of Patients With Serum Chemistry Laboratory Abnormalities: Uric Acid
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant uric acid levels post-baseline (normal range=4-8.5
mg/dL)
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28 days
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Number of Patients With Serum Chemistry Laboratory Abnormalities: Cholesterol
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant cholesterol levels post-baseline (normal range=0-199 mg/dL)
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28 days
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Number of Patients With Serum Chemistry Laboratory Abnormalities: Glucose
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant glucose levels post-baseline (normal range=70-125 mg/dL)
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28 days
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Number of Patients With Serum Chemistry Laboratory Abnormalities: Magnesium
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant magnesium levels post-baseline (normal range=1.2-2
mEq/L)
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28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: QT >500 Milliseconds (Msec)
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant ECG abnormalities (QT>500 msec) post-baseline
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28 days
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Number of Patients With Electrocardiogram (ECG) Abnormalities: QRS Interval
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant ECG abnormalities involving QRS interval (change > 100 msec)
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28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec
Periodo de tiempo: 28 days
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Incidence of potentially clinically significant ECG abnormalities (QTcB increase 30-60 msec)
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28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec
Periodo de tiempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities (QTcF increase 30-60 msec post-baseline)
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28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: ST Segment
Periodo de tiempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: ST Segment
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28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave
Periodo de tiempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: T wave
|
28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)
Periodo de tiempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: Right bundle branch block (RBBB), Left bundle branch block (LBBB), myocardial infarction (MI)
|
28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia
Periodo de tiempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: arrhythmia
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28 days
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Colaboradores
Investigadores
- Investigador principal: Joseph Verbalis, MD, Georgetown University, Washington, DC, 20007 USA
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de agosto de 2007
Finalización primaria (Actual)
1 de febrero de 2009
Finalización del estudio (Actual)
1 de marzo de 2009
Fechas de registro del estudio
Enviado por primera vez
25 de octubre de 2007
Primero enviado que cumplió con los criterios de control de calidad
26 de octubre de 2007
Publicado por primera vez (Estimar)
29 de octubre de 2007
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
28 de abril de 2011
Última actualización enviada que cumplió con los criterios de control de calidad
26 de abril de 2011
Última verificación
1 de abril de 2011
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 156-04-246
- INSIGHT
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .