Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients (INSIGHT)
26 aprile 2011 aggiornato da: 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.
Panoramica dello studio
Descrizione dettagliata
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 di studio
Interventistico
Iscrizione (Effettivo)
57
Fase
- Fase 3
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
-
-
California
-
Hawthorne, California, Stati Uniti, 90250
- Sarah. S. Olelewe, MD
-
Vista, California, Stati Uniti, 92083
- Progressive Clinical Research
-
-
Colorado
-
Colorado Springs, Colorado, Stati Uniti, 80907
- Pikes Peak Cardiology
-
-
Florida
-
Largo, Florida, Stati Uniti, 33770
- Innovative Research of West FL
-
Punta Gorda, Florida, Stati Uniti, 33950
- Coastal Nephrology Assoc. Research Center
-
-
Georgia
-
Conyers, Georgia, Stati Uniti, 30094
- Rockdale Medical Research Associates
-
-
Louisiana
-
Natchitoches, Louisiana, Stati Uniti, 71457
- Otis Barnum, DO
-
-
North Dakota
-
Fargo, North Dakota, Stati Uniti, 58106
- Lillestol Research, LLC
-
-
South Carolina
-
Columbia, South Carolina, Stati Uniti, 29201
- Carolina Research Associates
-
-
Tennessee
-
Lebanon, Tennessee, Stati Uniti, 37087
- Wayne O. Wells, MD
-
-
Texas
-
Houston, Texas, Stati Uniti, 77043
- Memorial Clinical Associates
-
-
Virginia
-
Charlottesville, Virginia, Stati Uniti, 22908
- Mitchell Rosner, MD
-
-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
50 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore placebo: 1
Placebo tablet given once a day for 21 days
|
Placebo tablet given once daily for 21 days
|
|
Comparatore attivo: 2
Tolvaptan 15 mg-60 mg tablet given once a day for 21 days.
|
15-60 mg oral tablet given once a day for 21 days.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests
Lasso di tempo: 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
|
baseline and Day 22
|
|
Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test
Lasso di tempo: 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
|
|
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
Lasso di tempo: 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
|
|
Change From Baseline in Overall Neurocognitive Composite Score
Lasso di tempo: 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
|
|
Change From Baseline in Gait Test (Timed Get-Up-and-Go Test)
Lasso di tempo: baseline and Day 22
|
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
|
baseline and Day 22
|
|
Change From Baseline in Postural Stability Test
Lasso di tempo: baseline and Day 22
|
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
|
baseline and Day 22
|
|
Change From Baseline in Serum Sodium; ITT Population
Lasso di tempo: Baseline and Day 22
|
Change from Baseline to Day 22 in Serum Sodium; ITT population
|
Baseline and Day 22
|
|
Number of Patients With Vital Sign Abnormalities: Blood Pressure
Lasso di tempo: 28 days
|
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
|
|
Number of Patients With Vital Sign Abnormalities: Pulse Rate
Lasso di tempo: 28 days
|
Incidence of abnormal pulse rate post-baseline [abnormal values: >=120 beats per minute (bpm) + increase of >=15 bpm; <=50 bpm + decrease of >=15 bpm]
|
28 days
|
|
Number of Patients With Vital Sign Abnormalities: Body Weight
Lasso di tempo: 28 days
|
Incidence of clinically significant body weight change post-baseline (defined as change upward or downward of >=7%)
|
28 days
|
|
Number of Patients With Vital Sign Abnormalities: Body Temperature
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant changes in body temperature post-baseline (defined as an increase of >=1.1 to >=38.3 degrees Celsius)
|
28 days
|
|
Number of Patients With Hematology Laboratory Abnormalities: Hemoglobin
Lasso di tempo: 28 days
|
Incidence of clinically significant hemoglobin abnormalities post-baseline (normal range=11.8-16.8
g/dL)
|
28 days
|
|
Number of Patients With Hematology Laboratory Abnormalities: Activated Partial Thromboplastin Time (aPTT)
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant Activated Partial Thromboplastin Time (aPTT) levels post-baseline (normal range=22-34 seconds)
|
28 days
|
|
Number of Patients With Hematology Laboratory Abnormalities: Lymphocytes
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant lymphocyte count post-baseline (normal range = 16-46%)
|
28 days
|
|
Number of Patients With Hematology Laboratory Abnormalities: Neutrophils
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant neutrophil count post-baseline (normal range=1.8-8
thousands/microliter)
|
28 days
|
|
Number of Patients With Serum Chemistry Laboratory Abnormalities: Blood Urea Nitrogen (BUN)
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant BUN levels post-baseline (normal range=7-30 mg/dL)
|
28 days
|
|
Number of Patients With Serum Chemistry Laboratory Abnormalities: Uric Acid
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant uric acid levels post-baseline (normal range=4-8.5
mg/dL)
|
28 days
|
|
Number of Patients With Serum Chemistry Laboratory Abnormalities: Cholesterol
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant cholesterol levels post-baseline (normal range=0-199 mg/dL)
|
28 days
|
|
Number of Patients With Serum Chemistry Laboratory Abnormalities: Glucose
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant glucose levels post-baseline (normal range=70-125 mg/dL)
|
28 days
|
|
Number of Patients With Serum Chemistry Laboratory Abnormalities: Magnesium
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant magnesium levels post-baseline (normal range=1.2-2
mEq/L)
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: QT >500 Milliseconds (Msec)
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities (QT>500 msec) post-baseline
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: QRS Interval
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities involving QRS interval (change > 100 msec)
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities (QTcB increase 30-60 msec)
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities (QTcF increase 30-60 msec post-baseline)
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: ST Segment
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: ST Segment
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: T wave
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: Right bundle branch block (RBBB), Left bundle branch block (LBBB), myocardial infarction (MI)
|
28 days
|
|
Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia
Lasso di tempo: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: arrhythmia
|
28 days
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Collaboratori
Investigatori
- Investigatore principale: Joseph Verbalis, MD, Georgetown University, Washington, DC, 20007 USA
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 agosto 2007
Completamento primario (Effettivo)
1 febbraio 2009
Completamento dello studio (Effettivo)
1 marzo 2009
Date di iscrizione allo studio
Primo inviato
25 ottobre 2007
Primo inviato che soddisfa i criteri di controllo qualità
26 ottobre 2007
Primo Inserito (Stima)
29 ottobre 2007
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
28 aprile 2011
Ultimo aggiornamento inviato che soddisfa i criteri QC
26 aprile 2011
Ultimo verificato
1 aprile 2011
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 156-04-246
- INSIGHT
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .