Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019) (DEFINE)
7 de diciembre de 2017 actualizado por: Merck Sharp & Dohme LLC
A 76-Week, Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Tolerability and Efficacy of Anacetrapib When Added to Ongoing Therapy With a Statin in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease
This study will evaluate the efficacy of anacetrapib (100 mg) for 24 weeks relative to placebo, on plasma concentrations of Low Density Lipoprotein Cholesterol and assess the safety and tolerability of anacetrapib (100 mg) in participants with CHD/CHD risk-equivalent disease on stable dose regimen of statin with or without other lipid-modifying therapy.
The two year extension to this study will further evaluate the long-term safety profile and efficacy of anacetrapib in CHD/CHD-risk equivalent patients who are on ongoing therapy with a statin with or without other lipid-modifying therapy.
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
The 76 week treatment period is followed by a 12 week reversibility phase which can be extended by up to another 12 weeks in order to allow participants who have completed their week 88 visit to continue in the study until the Extension study is ready to be implemented.
In the optional extension, participants will be assigned to the same treatment arm to which they were assigned in the base study. The total duration of the extension study will be up to 116 weeks; which will include a 2 year treatment period, followed by a 12 week reversal phase. A post-extension study follow-up phone call will be completed 12 weeks after discontinuation or completion of study treatment. Participants previously treated with anacetrapib or placebo will be invited in a 4:1 ratio in an optional extended reversal phase. The total duration of the extended reversal phase will be 1 year.
Participants previously treated with anacetrapib in the DEFINE study will be followed periodically for up to 4 years to determine plasma levels of anacetrapib. Participants will also be invited to participate in a sub-study consisting of one clinic visit to measure anacetrapib levels in the plasma and the subcutaneous adipose tissue.
ACRONYM: DEFINE= Determining the EFficacy and Tolerability of Cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib
Tipo de estudio
Intervencionista
Inscripción (Actual)
1623
Fase
- Fase 3
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 80 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
Base Study:
- Patient has Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease and is treated with a statin, with well controlled LDL-C
Extension Study:
- Patient has completed the base study including the reversibility period (i.e. 12 or to up to 24 weeks).
- Patient is on statin therapy ± lipid-modifying therapy since the end of the base study and planning to continue taking a statin throughout the study
Exclusion Criteria:
- History of heart failure, arrhythmias, heart attack, unstable angina, or stroke within 3 months prior to screening, uncontrolled blood pressure, uncontrolled high cholesterol or liver disease.
- History of mental instability, drug/alcohol abuse within the past 5 years
- Pregnant or breast-feeding
- History of cancer within the last 5 years
- HIV positive
- Donated blood products within 8 weeks
- Currently participating or have participated in a study with an investigational compound within the last 30 days
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 |
|---|---|
|
Experimental: Anacetrapib
Participants randomly assigned to anacetrapib in base study will continue same treatment if enrolled in study extension.
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Participants will receive one tablet of anacetrapib 100 mg once daily for 76 weeks.
Otros nombres:
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Comparador de placebos: Placebo
Participants randomly assigned to placebo in base study will continue same treatment if enrolled in study extension.
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Participants will receive one placebo tablet once daily for 76 weeks.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Change from baseline in Low Density Lipoprotein Cholesterol
Periodo de tiempo: Baseline and 24 weeks
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Baseline and 24 weeks
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Number of participants with hepatitis-related adverse experiences
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
|
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Number of participants with Alanine Transaminase consecutive elevations greater than or equal to 3xULN (Upper Limit of Normal)
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
|
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Number of participants with Aspartate Aminotransferase consecutive elevations greater than or equal to 3xULN
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with Creatine Phosphokinase elevations greater than or equal to 10xULN
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with Creatine Phosphokinase elevations greater than or equal 10xULN with muscle symptoms
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with sodium, chloride, or bicarbonate elevations greater than ULN
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with reduction in potassium levels less than LLN (Lower Limit of Normal)
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with myalgia
Periodo de tiempo: Through 88 weeks
|
Through 88 weeks
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Number of participants with rhabdomyolysis
Periodo de tiempo: Through 88 weeks
|
Through 88 weeks
|
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Number of participants with pre-specified adjudicated cardiovascular serious adverse events
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with death from any cause
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Number of participants with significant increase in Blood Pressure
Periodo de tiempo: Through 88 weeks
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Through 88 weeks
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Change from baseline in High Density Lipoprotein Cholesterol
Periodo de tiempo: Baseline, 24 weeks, and 76 weeks
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Baseline, 24 weeks, and 76 weeks
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Change from baseline in non-High Density Lipoprotein Cholesterol
Periodo de tiempo: Baseline, 24 weeks, and 76 weeks
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Baseline, 24 weeks, and 76 weeks
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Change from baseline in Apolipoprotein B
Periodo de tiempo: Baseline, 24 weeks, and 76 weeks
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Baseline, 24 weeks, and 76 weeks
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Change from baseline in Apolipoprotein A-1
Periodo de tiempo: Baseline, 24 weeks, and 76 weeks
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Baseline, 24 weeks, and 76 weeks
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Change from baseline in Low Density Lipoprotein Cholesterol
Periodo de tiempo: Baseline, 24 weeks, and 76 weeks
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Baseline, 24 weeks, and 76 weeks
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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.
Publicaciones Generales
- Brinton EA, Kher U, Shah S, Cannon CP, Davidson M, Gotto AM, Ashraf TB, McCrary Sisk C, Dansky H, Mitchel Y, Barter P; DEFINE Investigators. Effects of anacetrapib on plasma lipids in specific patient subgroups in the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) trial. J Clin Lipidol. 2015 Jan-Feb;9(1):65-71. doi: 10.1016/j.jacl.2014.10.005. Epub 2014 Nov 4.
- Gotto AM Jr, Kher U, Chatterjee MS, Liu Y, Li XS, Vaidya S, Cannon CP, Brinton EA, Moon JE, Shah S, Dansky HM, Mitchel Y, Barter P; DEFINE Investigators. Lipids, safety parameters, and drug concentrations after an additional 2 years of treatment with anacetrapib in the DEFINE study. J Cardiovasc Pharmacol Ther. 2014 Nov;19(6):543-9. doi: 10.1177/1074248414529621. Epub 2014 Apr 14.
- Cannon CP, Shah S, Dansky HM, Davidson M, Brinton EA, Gotto AM, Stepanavage M, Liu SX, Gibbons P, Ashraf TB, Zafarino J, Mitchel Y, Barter P; Determining the Efficacy and Tolerability Investigators. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010 Dec 16;363(25):2406-15. doi: 10.1056/NEJMoa1009744. Epub 2010 Nov 17.
- Cannon CP, Dansky HM, Davidson M, Gotto AM Jr, Brinton EA, Gould AL, Stepanavage M, Liu SX, Shah S, Rubino J, Gibbons P, Hermanowski-Vosatka A, Binkowitz B, Mitchel Y, Barter P; DEFINE investigators. Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib. Am Heart J. 2009 Oct;158(4):513-519.e3. doi: 10.1016/j.ahj.2009.07.028.
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)
24 de marzo de 2008
Finalización primaria (Actual)
2 de julio de 2009
Finalización del estudio (Actual)
23 de noviembre de 2017
Fechas de registro del estudio
Enviado por primera vez
23 de mayo de 2008
Primero enviado que cumplió con los criterios de control de calidad
27 de mayo de 2008
Publicado por primera vez (Estimar)
28 de mayo de 2008
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
11 de diciembre de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
7 de diciembre de 2017
Última verificación
1 de diciembre de 2017
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Arteriosclerosis
- Enfermedades arteriales oclusivas
- Enfermedades cardíacas
- Enfermedad de la arteria coronaria
- Isquemia miocardica
- Enfermedad coronaria
- Mecanismos moleculares de acción farmacológica
- Antimetabolitos
- Agentes Anticolesterolémicos
- Agentes hipolipidémicos
- Agentes reguladores de lípidos
- Anacetrapib
Otros números de identificación del estudio
- 0859-019
- 2007_648 (Otro identificador: Merck Study Number)
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. .
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