Pharmacokinetics of LCQ908 in Patients With Hepatic Impairment
16 de diciembre de 2020 actualizado por: Novartis Pharmaceuticals
An Open-label, Single Dose, Parallel-group Study to Evaluate the Pharmacokinetics of LCQ908 in Patients With Mild, Moderate and Severe Hepatic Impairment Compared to Age, Gender and Weight-matched Healthy Volunteers.
This study will compare the pharmacokinetics of LCQ908 in subjects with varying degrees of hepatic impairment to healthy subjects.
Descripción general del estudio
Tipo de estudio
Intervencionista
Inscripción (Actual)
53
Fase
- Fase 1
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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Florida
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Miami, Florida, Estados Unidos, 33136
- Novartis Investigative Site
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Orlando, Florida, Estados Unidos, 32809
- Novartis Investigative Site
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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
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Descripción
Inclusion criteria:
Individuals with hepatic impairment only
• Hepatic impairment evidenced by a Child-Pugh score
- Mild hepatic impairment defined Child-Pugh Class A (5-6 points)
- Moderate hepatic impairment defined Child-Pugh Class B (7-9 points)
- Severe hepatic impairment defined Child-Pugh Class C (10-15 points).
Healthy subjects only
• Good health determined.
Exclusion criteria:
All Individuals
- A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.
- Female subjects must be of non child bearing potential or use an effective method of contraception.
Individuals with hepatic impairment
- History of drug or alcohol abuse within 3 months prior to dosing.
- History or presence of significant uncontrolled disease of any major organ class.
- Any surgical or medical condition other than hepatic impairment which might alter the drug metabolism.
Healthy subjects
- History or presence of significant uncontrolled disease of any major organ class.
- Any surgical or medical condition other than hepatic impairment which might alter the drug metabolism.
- History or presence of hepatitis B or C and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at screening.
Other protocol-defined inclusion/exclusion criteria may apply.
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: Otro
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: LCQ908 (mild hepatic impairment plus healthy volunteers)
Healthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with mild hepatic impairment and will receive a single dose of LCQ908.
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Participants will receive a single oral dose of LCQ908
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Experimental: LCQ908 (moderate hepatic impairment plus healthy volunteers)
Healthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with moderate hepatic impairment and will receive a single dose of LCQ908.
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Participants will receive a single oral dose of LCQ908
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Experimental: LCQ908 (severe hepatic impairment plus healthy volunteers)
Healthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with severe hepatic impairment and will receive a single dose of LCQ908.
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Participants will receive a single oral dose of LCQ908
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 for part I of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 for part I of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Maximum plasma concentration of LCQ908 (Cmax) for Part I of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part I of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 for Part II of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 for Part II of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Maximum plasma concentration of LCQ908 (Cmax) for Part II of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part II of the study
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of participants with adverse events, serious adverse events and death (for both Part I and Part II)
Periodo de tiempo: Day 28
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Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen.
Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization,cause persistent or significant disability/incapacity, result in congenital abnormalities or birth defects,or are other conditions which in judgment of investigators represent significant hazards.
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Day 28
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Time to maximum plasma concentration of LCQ908 (Tmax) (for both Part I and Part II)
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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The time required for the concentration of the drug to reach half of its original value (T1/2) (for both Part I and Part II)
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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The apparent volume of distribution of LCQ908 during the terminal elimination phase following extra vascular administration (Vz/F) (for both Part I and Part II)
Periodo de tiempo: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II.
Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
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LCQ908 protein binding: unbound area under curve (AUCu) of LCQ908 (for both Part I and Part II)
Periodo de tiempo: 10 and 24 hours post dose
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This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II.
Blood will be collected 10 and 24 hours post dosing.
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10 and 24 hours post dose
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LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908 (for both Part I and Part II)
Periodo de tiempo: 10 and 24 hours
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This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II.
Blood will be collected 10 and 24 hours post dosing.
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10 and 24 hours
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LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration (for both Part I and Part II)
Periodo de tiempo: 10 and 24 hours
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This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II.
Blood will be collected 10 and 24 hours post dosing.
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10 and 24 hours
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
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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 abril de 2012
Finalización primaria (Actual)
1 de abril de 2013
Finalización del estudio (Actual)
1 de abril de 2013
Fechas de registro del estudio
Enviado por primera vez
7 de mayo de 2012
Primero enviado que cumplió con los criterios de control de calidad
8 de mayo de 2012
Publicado por primera vez (Estimar)
9 de mayo de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
19 de diciembre de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
16 de diciembre de 2020
Última verificación
1 de mayo de 2013
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CLCQ908B2101
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. .