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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. marts 2016 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

680

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
      • Darlinghurst, Australien
      • Prahran, Australien
      • Surry Hills, Australien
  • Belgien
      • Antwerpen, Belgien
      • Brussels, Belgien
      • Gent, Belgien
      • Leuven, Belgien
  • Brasilien
      • Campinas, Brasilien
      • Distrito Barao Geraldo-Campina, Brasilien
      • Pinheiros, Brasilien
      • Recife, Brasilien
      • Sao Paulo, Brasilien
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Chile
      • Providencia, Chile
      • Santiago, Chile
  • Costa Rica
      • San Jose, Costa Rica
  • Den Russiske Føderation
      • Moscow N/A, Den Russiske Føderation
      • Saint-Petersburg, Den Russiske Føderation
      • Smolensk, Den Russiske Føderation
      • Voronezh, Den Russiske Føderation
  • Det Forenede Kongerige
      • London, Det Forenede Kongerige
      • Manchester, Det Forenede Kongerige
  • Forenede Stater
    • California
      • Long Beach, California, Forenede Stater
      • Los Angeles, California, Forenede Stater
      • San Francisco, California, Forenede Stater
    • District of Columbia
      • Washington, District of Columbia, Forenede Stater
    • Florida
      • Atlantis, Florida, Forenede Stater
      • Miami, Florida, Forenede Stater
      • Miami Beach, Florida, Forenede Stater
      • Orlando, Florida, Forenede Stater
      • Tampa, Florida, Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater
    • Kentucky
      • Lexington, Kentucky, Forenede Stater
    • Maryland
      • Baltimore, Maryland, Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater
      • Springfield, Massachusetts, Forenede Stater
    • Michigan
      • Detroit, Michigan, Forenede Stater
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater
    • New Jersey
      • Newark, New Jersey, Forenede Stater
    • New York
      • Bronx, New York, Forenede Stater
      • Flushing, New York, Forenede Stater
      • New York, New York, Forenede Stater
      • Rochester, New York, Forenede Stater
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater
    • Texas
      • Dallas, Texas, Forenede Stater
      • Houston, Texas, Forenede Stater
      • Longview, Texas, Forenede Stater
  • Frankrig
      • Clamart, Frankrig
      • Le Kremlin Bicetre, Frankrig
      • Montpellier, Frankrig
      • Paris, Frankrig
  • Indien
      • Chennai, Indien
      • Nagpur, Indien
  • Kina
      • Beijing, Kina
      • Guangzhou, Kina
      • Shanghai, Kina
  • Mexico
      • Guadalajara N/A, Mexico
      • Mexico City, Mexico
  • Panama
      • Panama, Panama
      • Panama City N/A, Panama
  • Portugal
      • Porto, Portugal
  • Puerto Rico
      • San Juan, Puerto Rico
  • Spanien
      • Barcelona, Spanien
      • Barcelona N/A, Spanien
      • Elche, Spanien
      • Madrid, Spanien
  • Sydafrika
      • Bloemfontein, Sydafrika
      • Cape Town, Sydafrika
      • Dundee, Sydafrika
      • Johannesburg, Sydafrika
      • Pretoria N/A, Sydafrika
      • Westdene Johannesburg Gauteng, Sydafrika
  • Thailand
      • Bangkok, Thailand
  • Tyskland
      • Berlin, Tyskland
      • Essen, Tyskland
      • Frankfurt, Tyskland
      • Hamburg, Tyskland
      • Hannover, Tyskland
      • Köln, Tyskland
      • Mannheim, Tyskland

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 99 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: 002
efavirenz 600 mg tablet once daily for 96 weeks
Medicin: efavirenz
600 mg tablet once daily for 96 weeks
Eksperimentel: 001
TMC278 25 mg tablet once daily for 96 weeks
Medicin: TMC278
25 mg tablet én gang dagligt i 96 uger

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Gennemsnitlig ændring fra baseline til uge 48 og uge 96 i absolutte og relative CD4+-celleantal (ved brug af imputerede data)
Tidsramme: Baseline, uge ​​48 og uge 96
Ændring fra baseline i CD4+-celletal blev imputeret i tilfælde af manglende værdier: i tilfælde af for tidlig seponering blev data imputeret med basislinjeværdien efter seponering (dvs. change=0, Non-Completer [NC] = Failure); ellers blev den sidste fremførte observation anvendt.
Baseline, uge ​​48 og uge 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48
Tidsramme: 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
Tidsramme: Week 96
Week 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96
Tidsramme: Week 96
Week 96
Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96).
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juni 2008

Primær færdiggørelse (Faktiske)

1. januar 2010

Studieafslutning (Faktiske)

1. februar 2012

Datoer for studieregistrering

Først indsendt

11. oktober 2007

Først indsendt, der opfyldte QC-kriterier

11. oktober 2007

Først opslået (Skøn)

15. oktober 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

1. april 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. marts 2016

Sidst verificeret

1. marts 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CR002704
  • TMC278-TIDP6-C215 (Anden identifikator: Tibotec Pharmaceuticals, Ireland)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med HIV-infektioner

Kliniske forsøg med TMC278

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