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TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

3 de marzo de 2016 actualizado por: Tibotec Pharmaceuticals, Ireland

A Phase III, Randomized, Double-blind Trial of TMC278 25mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Background Regimen Containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-naive HIV-1 Infected Subjects.

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics and Medical resource utilization and treatment adherence.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL, in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.

Tipo de estudio

Intervencionista

Inscripción (Actual)

680

Fase

  • Fase 3

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

  • Alemania
      • Berlin, Alemania
      • Essen, Alemania
      • Frankfurt, Alemania
      • Hamburg, Alemania
      • Hannover, Alemania
      • Köln, Alemania
      • Mannheim, Alemania
  • Australia
      • Darlinghurst, Australia
      • Prahran, Australia
      • Surry Hills, Australia
  • Brasil
      • Campinas, Brasil
      • Distrito Barao Geraldo-Campina, Brasil
      • Pinheiros, Brasil
      • Recife, Brasil
      • Sao Paulo, Brasil
  • Bélgica
      • Antwerpen, Bélgica
      • Brussels, Bélgica
      • Gent, Bélgica
      • Leuven, Bélgica
  • Canadá
    • Alberta
      • Calgary, Alberta, Canadá
    • British Columbia
      • Vancouver, British Columbia, Canadá
    • Manitoba
      • Winnipeg, Manitoba, Canadá
    • Ontario
      • Toronto, Ontario, Canadá
    • Quebec
      • Montreal, Quebec, Canadá
  • Chile
      • Providencia, Chile
      • Santiago, Chile
  • Costa Rica
      • San Jose, Costa Rica
  • España
      • Barcelona, España
      • Barcelona N/A, España
      • Elche, España
      • Madrid, España
  • Estados Unidos
    • California
      • Long Beach, California, Estados Unidos
      • Los Angeles, California, Estados Unidos
      • San Francisco, California, Estados Unidos
    • District of Columbia
      • Washington, District of Columbia, Estados Unidos
    • Florida
      • Atlantis, Florida, Estados Unidos
      • Miami, Florida, Estados Unidos
      • Miami Beach, Florida, Estados Unidos
      • Orlando, Florida, Estados Unidos
      • Tampa, Florida, Estados Unidos
    • Illinois
      • Chicago, Illinois, Estados Unidos
    • Kentucky
      • Lexington, Kentucky, Estados Unidos
    • Maryland
      • Baltimore, Maryland, Estados Unidos
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos
      • Springfield, Massachusetts, Estados Unidos
    • Michigan
      • Detroit, Michigan, Estados Unidos
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos
    • New Jersey
      • Newark, New Jersey, Estados Unidos
    • New York
      • Bronx, New York, Estados Unidos
      • Flushing, New York, Estados Unidos
      • New York, New York, Estados Unidos
      • Rochester, New York, Estados Unidos
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos
    • Texas
      • Dallas, Texas, Estados Unidos
      • Houston, Texas, Estados Unidos
      • Longview, Texas, Estados Unidos
  • Federación Rusa
      • Moscow N/A, Federación Rusa
      • Saint-Petersburg, Federación Rusa
      • Smolensk, Federación Rusa
      • Voronezh, Federación Rusa
  • Francia
      • Clamart, Francia
      • Le Kremlin Bicetre, Francia
      • Montpellier, Francia
      • Paris, Francia
  • India
      • Chennai, India
      • Nagpur, India
  • México
      • Guadalajara N/A, México
      • Mexico City, México
  • Panamá
      • Panama, Panamá
      • Panama City N/A, Panamá
  • Porcelana
      • Beijing, Porcelana
      • Guangzhou, Porcelana
      • Shanghai, Porcelana
  • Portugal
      • Porto, Portugal
  • Puerto Rico
      • San Juan, Puerto Rico
  • Reino Unido
      • London, Reino Unido
      • Manchester, Reino Unido
  • Sudáfrica
      • Bloemfontein, Sudáfrica
      • Cape Town, Sudáfrica
      • Dundee, Sudáfrica
      • Johannesburg, Sudáfrica
      • Pretoria N/A, Sudáfrica
      • Westdene Johannesburg Gauteng, Sudáfrica
  • Tailandia
      • Bangkok, Tailandia

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 99 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Patient with documented HIV-1 infection
  • Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening
  • Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure)
  • Patient's virus is sensitive to the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment
  • Patient agrees not to start ART before the baseline visit
  • Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment regimen.

Exclusion Criteria:

  • Previous use of ANY ARV drug for ANY length of time
  • Any documented evidence of NNRTI resistance associated mutations in patient's HIV
  • Category C AIDS defining illness, except, Stable Kaposi Sarcoma Wasting syndrome if not progressive
  • Pneumocystis carinii pneumonia (PCP) that is considered not cured
  • Active TB
  • Allergy or hypersensitivity to study or background ARTs
  • Specific grade 3 or 4 toxicity
  • Kidney impairment: calculated creatinine clearance <50 ml/min

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: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: 002
efavirenz 600 mg tablet once daily for 96 weeks
Droga: efavirenz
600 mg tablet once daily for 96 weeks
Experimental: 001
TMC278 25 mg tablet once daily for 96 weeks
Droga: TMC278
Comprimido de 25 mg una vez al día durante 96 semanas

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48
Periodo de tiempo: Week 48
Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).
Week 48

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Cambio medio desde el inicio hasta la semana 48 y la semana 96 en los recuentos absolutos y relativos de células CD4+ (usando datos imputados)
Periodo de tiempo: Línea de base, semana 48 y semana 96
Se imputó el cambio desde el valor inicial en el recuento de células CD4+ en caso de que faltaran valores: en caso de interrupción prematura, los datos se imputaron con el valor inicial después de la interrupción (es decir, change=0, Non-Complete [NC] = Fallo); de lo contrario, se aplicó la última observación llevada adelante.
Línea de base, semana 48 y semana 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48
Periodo de tiempo: Week 48
The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/mL (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/mL in the Wk 48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/mL and subjects who had a switch in background regimen that was not permitted by the protocol.
Week 48
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96
Periodo de tiempo: Week 96
Week 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96
Periodo de tiempo: Week 96
Week 96
Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96).
Periodo de tiempo: Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per mL at the last on-treatment post-Week 96 visit.
Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 48
Periodo de tiempo: Week 48
Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).
Week 48
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 96
Periodo de tiempo: Week 96
Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 96. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).
Week 96
Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
Periodo de tiempo: Week 96
Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Week 96

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Tibotec Pharmaceuticals, Ireland

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

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 junio de 2008

Finalización primaria (Actual)

1 de enero de 2010

Finalización del estudio (Actual)

1 de febrero de 2012

Fechas de registro del estudio

Enviado por primera vez

11 de octubre de 2007

Primero enviado que cumplió con los criterios de control de calidad

11 de octubre de 2007

Publicado por primera vez (Estimar)

15 de octubre de 2007

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

1 de abril de 2016

Última actualización enviada que cumplió con los criterios de control de calidad

3 de marzo de 2016

Última verificación

1 de marzo de 2016

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • CR002704
  • TMC278-TIDP6-C215 (Otro identificador: Tibotec Pharmaceuticals, Ireland)

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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