Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients (INSIGHT)
26. dubna 2011 aktualizováno: 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.
Přehled studie
Detailní popis
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).
Typ studie
Intervenční
Zápis (Aktuální)
57
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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California
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Hawthorne, California, Spojené státy, 90250
- Sarah. S. Olelewe, MD
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Vista, California, Spojené státy, 92083
- Progressive Clinical Research
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Colorado
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Colorado Springs, Colorado, Spojené státy, 80907
- Pikes Peak Cardiology
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Florida
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Largo, Florida, Spojené státy, 33770
- Innovative Research of West FL
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Punta Gorda, Florida, Spojené státy, 33950
- Coastal Nephrology Assoc. Research Center
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Georgia
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Conyers, Georgia, Spojené státy, 30094
- Rockdale Medical Research Associates
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Louisiana
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Natchitoches, Louisiana, Spojené státy, 71457
- Otis Barnum, DO
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North Dakota
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Fargo, North Dakota, Spojené státy, 58106
- Lillestol Research, LLC
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South Carolina
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Columbia, South Carolina, Spojené státy, 29201
- Carolina Research Associates
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Tennessee
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Lebanon, Tennessee, Spojené státy, 37087
- Wayne O. Wells, MD
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Texas
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Houston, Texas, Spojené státy, 77043
- Memorial Clinical Associates
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Virginia
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Charlottesville, Virginia, Spojené státy, 22908
- Mitchell Rosner, MD
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
50 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Komparátor placeba: 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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Aktivní komparátor: 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.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)
Časové okno: baseline and Day 22
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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
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baseline and Day 22
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests
Časové okno: 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
Časové okno: baseline and Day 22
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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
Časové okno: baseline and Day 22
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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
Časové okno: baseline and Day 22
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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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
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28 days
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Number of Patients With Vital Sign Abnormalities: Pulse Rate
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 28 days
|
Incidence of potentially clinically significant ECG abnormalities involving QRS interval (change > 100 msec)
|
28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec
Časové okno: 28 days
|
Incidence of potentially clinically significant ECG abnormalities (QTcB increase 30-60 msec)
|
28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec
Časové okno: 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
Časové okno: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: ST Segment
|
28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave
Časové okno: 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)
Časové okno: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: Right bundle branch block (RBBB), Left bundle branch block (LBBB), myocardial infarction (MI)
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28 days
|
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Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia
Časové okno: 28 days
|
Incidence of potentially clinically significant ECG abnormalities: arrhythmia
|
28 days
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Joseph Verbalis, MD, Georgetown University, Washington, DC, 20007 USA
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. srpna 2007
Primární dokončení (Aktuální)
1. února 2009
Dokončení studie (Aktuální)
1. března 2009
Termíny zápisu do studia
První předloženo
25. října 2007
První předloženo, které splnilo kritéria kontroly kvality
26. října 2007
První zveřejněno (Odhad)
29. října 2007
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
28. dubna 2011
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
26. dubna 2011
Naposledy ověřeno
1. dubna 2011
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 156-04-246
- INSIGHT
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .