Multiple Dose Study in Heart Failure of BAY 1067197 (PARSiFAL)
19 de junio de 2019 actualizado por: Bayer
A Double Blinded, Placebo Controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics and Acute Cardiovascular Responses of a 7 Day Oral Treatment With the Partial Adenosine A1 Receptor Agonist BAY1067197 in Patients With Chronic Systolic Heart Failure: the PARSiFAL-pilot Study.
This is a study to investigate the safety, tolerability and early effects on cardiac function of the partial A1 agonist BAY1067197 in patients with chronic heart failure.
BAY1067197 will be applied once daily over 7 days in addition to standard therapy including a beta-blocker.
The aim of the study is to assess if a 7 day treatment with BAY1067197 is well tolerated when given on top of standard therapy for heart failure.
Furthermore, the study aims to assess if cardiac function improves in the early course of therapy.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
31
Fase
- Fase 2
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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Berlin, Alemania, 13353
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Lombardia
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Bergamo, Lombardia, Italia, 24127
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Brescia, Lombardia, Italia, 25123
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Milano, Lombardia, Italia, 20138
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Groningen, Países Bajos, 9713 GZ
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Wroclaw, Polonia, 50-981
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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
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
- Inclusion Criteria:
- Clinical diagnosis of chronic systolic heart failure of ischemic or non-ischemic etiology:(New York Heart Association)NYHA class I-III and treatment with standard pharmacological therapy for the treatment of systolic heart failure including β-blocker ≥ 4 weeks prior to randomization
- Left ventricular ejection fraction ≤ 40%: by any imaging technique within the last 3 months will be accepted for screening purposes but will be verified by baseline CMR(Cardiac Magnetic Resonance Tomography)
- Sinus rhythm for at least 4 weeks prior to randomization
- No planned changes to heart failure related drug therapy for the duration of study drug treatment
- Substantial dysfunctional but viable myocardium as demonstrated by the baseline CMR: Based on a standard 17-segment model (AHA - American Heart Association), 3 or more segments require demonstration of dysfunction (defined by visible assessment of the performing investigator) and viability (defined as < 25% of segment area with scar burden - in patients with CAD (Coronary Artery Disease) or no (i.e. zero) scar burden in patients without CAD [idiopathic CM patient])
- Men or confirmed postmenopausal women or women without childbearing potential.
- Age: 18 to 75 years (inclusive) at the first screening visit.
- Body Mass Index (BMI) :above /equal 18.0 and below/equal 34.9kg/m²
- Exclusion Criteria:
- Atrial fibrillation / atrial flutter within the last 4 weeks prior to randomization or currently persistent/permanent atrial fibrillation / atrial flutter
- Primary valvular disease (severe valvular disease) with planned valve repair or replacement
- Non-idiopathic non-ischemic causes for cardiomyopathy (constrictive, restrictive, or hypertrophic cardiomyopathy; acute myocarditis)
- Listing for heart transplantation and/or anticipated/implanted ventricular assist device Clinically relevant ventricular arrhythmias within the last 2 months (sustained ventricular tachycardia, ventricular flutter or fibrillation), based on either medical history or ICD-testing results (if applicable)
- Unstable cardiac condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV within 4 weeks prior to randomization
- Coronary revascularization within 4 weeks prior to randomization or if revascularization is anticipated or needed
- Current permanent or intermittent AV-Block > I° or history of AV-Block > I° within six months before enrollment
- PR duration ≥ 300 ms
- Acute Coronary Syndrome (defined as unstable angina [UA], non-ST elevation myocardial infarction [NSTEMI], ST elevation myocardial infarction [STEMI]) within 2 months prior to randomization
- Subjects with untreated hyperthyroidism or hypothyroidism and non-stable thyroid function (intake of stable thyroid hormone substitution allowed)
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: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador de placebos: Placebo
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5 mg / or 10 mg / or 20 mg Placebo for 7 d treatment once daily as oral application
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Comparador activo: BAY1067197 (10 mg)
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10 mg BAY1067197 for 7 d treatment once daily as oral application
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Comparador activo: BAY1067197
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The dose escalation to the second dose step will proceed only if the previous dose step has shown acceptable safety and tolerability 5 mg / or 10 mg / or 20 mg BAY1067197 for 7 d treatment as oral application.
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Comparador de placebos: Placebo (10 mg)
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10 mg Placebo for 7 d treatment once daily as oral application
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Subjects With Relevant Changes in Heart Rate
Periodo de tiempo: From the start of study treatment up to Day 29
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Heart rate was measured by monitor measurements after 30 minutes resting in a supine position.
The relevant changes in heart rate were recorded and analysed.
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From the start of study treatment up to Day 29
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Number of Subjects With Relevant Changes in Blood Pressure
Periodo de tiempo: From the start of study treatment up to Day 29
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Blood pressure was measured by monitor measurements after 30 minutes resting in a supine position.
The relevant changes in blood pressure were recorded and analysed.
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From the start of study treatment up to Day 29
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Number of Subjects With More than First Degree Atrio-Ventricular (AV) Block
Periodo de tiempo: After 7 day tratment and day 28
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A complete standard 12-lead ECG was recorded and evaluated parameters such as heart rate, PR/PQinterval, QRSD interval, QT interval (uncorrected).
Clinically relevant findings in ECG such as a second degree AV-block Mobitz type I (Wenkebach), Mobitz type II - or any third-degree AV block were recorded and reported.
A 24-hour Holter ECG was recorded with a standard Holter ECG recorder for the purpose of detecting AV blocks, no higher degree AV blocks > 1 or clinically relevant effect on HR were observed during Holter monitoring periods.
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After 7 day tratment and day 28
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Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Periodo de tiempo: Baseline to day 7
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The change in LVEF between the post and the pre-treatment measurements were analyzed using Bayesian statistics to quantify the difference between BAY1067197 treatment and placebo measured by CMR.
LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart.
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Baseline to day 7
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Maximum Observed Concentration of BAY84-3174 in Plasma (Cmax) After First Dose of BAY1067197
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Maximum observed BAY84-3174 concentration in plasma, directly taken from analytical data.
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose (Cmax/D) After First Dose of BAY1067197
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Maximum observed drug concentration, directly taken from analytical data, divided by dose.
Geometric mean and %CV were reported.
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval (AUCtau) After First Dose of BAY1067197
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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AUCtau is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after the first dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose (AUCtau/D) After First Dose of BAY1067197
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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AUCtau/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose after the first dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Maximum Observed Concentration of BAY84-3174 in Plasma (Cmax,md) After Multiple Dose Administration During a Dosing Interval
Periodo de tiempo: Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Cmax,md is defined as maximum observed drug concentration in plasma after multiple-dose administrations during a dosing interval directly taken from analytical data.Geometric mean and %CV were reported.
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Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose (Cmax,md/D) After Multiple Dose Administration During a Dosing Interval
Periodo de tiempo: Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Maximum observed drug concentration, directly taken from analytical data divided by dose after multiple doses.
Geometric mean and %CV were reported.
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Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Area Under the Concentration Versus Time Curve of BAY84-3174 During any Dosing Interval (AUCtau,md) After Multiple Dose Administration
Periodo de tiempo: Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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AUCtau,md is defined as area under the plasma concentration time profile from time zero during the dosing interval after multiple-dose administrations and dosing interval was 24 h for both arms. Geometric mean and %CV were reported. |
Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Area Under the Concentration Versus Time Curve of BAY84-3174 During any Dosing Interval Divided by Dose (AUCtau,md/D) After Multiple Dose Administration
Periodo de tiempo: Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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AUCtau,md/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dose of administrations divided by dose and dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
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Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Changes From Baseline for Wall Motion Score Index at Day (WMSI) as Measured by Cardiac Magnetic Resonance at Day 7
Periodo de tiempo: Baseline to day 7
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Wall motion score index will cover the changes in wall motion score from baseline also.
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Baseline to day 7
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Number of Subjects With Clinically Relevant Changes Observed in Echocardiography Parameters
Periodo de tiempo: Baseline, Day 6 and 15
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Septal mitral annulus (e' septal), Lateral mitral annulus (e' lateral), E/e' average (average of e' lateral and e' septal), E/e' Lateral ratio, E/e' Septal ratio, Peak early doppler transmitral flow velocity (E), Peak atrial doppler transmitral flow velocity (A), E/A Ratio, Deceleration time (DT), Global longitudinal strain, Cardiac output, Stroke volume, Stroke volume index, Peak systolic tissue Doppler Velocity (Smax), Left ventricular end-systolic volume (LVESV), Left ventricular enddiastolic volume (LVEDV), Left atrial volume index (LAVI), Peak pulmonary systolic pressure (PAPsys).
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Baseline, Day 6 and 15
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Number of Subjects With Clinically Relevant Changes Observed in Biomarkers
Periodo de tiempo: Baseline up to Day 15
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N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renin, mid-region pro-atrial natriuretic peptide (MR-proANP) are biomarkers which show effect on neurohormones.
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Baseline up to Day 15
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Time to Reach Maximum Observed Concentration of BAY84-3174 in Plasma (tmax) After First Dose of BAY1067197
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Time to reach maximum drug concentration in the measured matrix, directly taken from analytical data
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose per Body Weight (AUCtau,md,norm) After Multiple Dose Administration
Periodo de tiempo: Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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AUCtau,md,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dosing divided by dose per body weight.
The dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
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Day 7: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Maximum Observed Concentration of BAY84-3174 in Plasma Divided by Dose per Body Weight (Cmax,md,norm) After Multiple Dose Administration
Periodo de tiempo: Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Cmax,md,norm defined as maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations during a dosing interval divided by dose per body weight.
Geometric mean and %CV were reported.
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Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Time to Reach Maximum Observed Concentration of BAY84-3174 in Plasma (tmax,md) After Multiple Dose Administration
Periodo de tiempo: Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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tmax,md defines as time to reach maximum drug concentration in the measured matrix after multiple dose administrations directly taken from analytical data.
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Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Half-Life Associated With the Terminal Slope (t1/2,md) After Multiple-Dose Administration
Periodo de tiempo: Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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t1/2,md is defiend as time to reach maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations.
Geometric mean and %CV were reported.
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Day 7: pre dose and 0.5, 1, 2, 3, 4, 6 and 12 hours post dose; Day 8, Day 14, Day 22 and Day 29
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Maximum Observed Concentration of BAY84-3174 in Plasma After First Dose Divided by Dose per Body Weight (Cmax,norm)
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Cmax,norm is defined as maximum observed drug concentration in plasma after the first dose divided by dose per body weight.
Geometric mean and %CV were reported.
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Area Under the Concentration Versus Time Curve of BAY84-3174 for the Dosing Interval Divided by Dose per Body Weight (AUCtau,norm) After First Dose of BAY1067197
Periodo de tiempo: Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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AUCtau,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose per body weight after the first dose.
Dosing interval was 24 h for both arms.
Geometric mean and %CV were reported.
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Day 1: pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
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 (Actual)
28 de enero de 2014
Finalización primaria (Actual)
29 de enero de 2015
Finalización del estudio (Actual)
2 de abril de 2015
Fechas de registro del estudio
Enviado por primera vez
17 de enero de 2014
Primero enviado que cumplió con los criterios de control de calidad
17 de enero de 2014
Publicado por primera vez (Estimar)
20 de enero de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
21 de junio de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
19 de junio de 2019
Última verificación
1 de junio de 2019
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 16782
- 2013-002522-23 (Número EudraCT)
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. .