Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

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. mars 2016 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

680

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Australia
      • Darlinghurst, Australia
      • Prahran, Australia
      • Surry Hills, Australia
  • Belgia
      • Antwerpen, Belgia
      • Brussels, Belgia
      • Gent, Belgia
      • Leuven, Belgia
  • Brasil
      • Campinas, Brasil
      • Distrito Barao Geraldo-Campina, Brasil
      • Pinheiros, Brasil
      • Recife, Brasil
      • Sao Paulo, Brasil
  • 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 føderasjonen
      • Moscow N/A, Den russiske føderasjonen
      • Saint-Petersburg, Den russiske føderasjonen
      • Smolensk, Den russiske føderasjonen
      • Voronezh, Den russiske føderasjonen
  • Forente stater
    • California
      • Long Beach, California, Forente stater
      • Los Angeles, California, Forente stater
      • San Francisco, California, Forente stater
    • District of Columbia
      • Washington, District of Columbia, Forente stater
    • Florida
      • Atlantis, Florida, Forente stater
      • Miami, Florida, Forente stater
      • Miami Beach, Florida, Forente stater
      • Orlando, Florida, Forente stater
      • Tampa, Florida, Forente stater
    • Illinois
      • Chicago, Illinois, Forente stater
    • Kentucky
      • Lexington, Kentucky, Forente stater
    • Maryland
      • Baltimore, Maryland, Forente stater
    • Massachusetts
      • Boston, Massachusetts, Forente stater
      • Springfield, Massachusetts, Forente stater
    • Michigan
      • Detroit, Michigan, Forente stater
    • Minnesota
      • Minneapolis, Minnesota, Forente stater
    • New Jersey
      • Newark, New Jersey, Forente stater
    • New York
      • Bronx, New York, Forente stater
      • Flushing, New York, Forente stater
      • New York, New York, Forente stater
      • Rochester, New York, Forente stater
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater
    • Texas
      • Dallas, Texas, Forente stater
      • Houston, Texas, Forente stater
      • Longview, Texas, Forente stater
  • Frankrike
      • Clamart, Frankrike
      • Le Kremlin Bicetre, Frankrike
      • Montpellier, Frankrike
      • Paris, Frankrike
  • India
      • Chennai, India
      • Nagpur, India
  • 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
  • Spania
      • Barcelona, Spania
      • Barcelona N/A, Spania
      • Elche, Spania
      • Madrid, Spania
  • Storbritannia
      • London, Storbritannia
      • Manchester, Storbritannia
  • Sør-Afrika
      • Bloemfontein, Sør-Afrika
      • Cape Town, Sør-Afrika
      • Dundee, Sør-Afrika
      • Johannesburg, Sør-Afrika
      • Pretoria N/A, Sør-Afrika
      • Westdene Johannesburg Gauteng, Sør-Afrika
  • Thailand
      • Bangkok, Thailand
  • Tyskland
      • Berlin, Tyskland
      • Essen, Tyskland
      • Frankfurt, Tyskland
      • Hamburg, Tyskland
      • Hannover, Tyskland
      • Köln, Tyskland
      • Mannheim, Tyskland

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 99 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: 002
efavirenz 600 mg tablet once daily for 96 weeks
Legemiddel: efavirenz
600 mg tablet once daily for 96 weeks
Eksperimentell: 001
TMC278 25 mg tablet once daily for 96 weeks
Legemiddel: TMC278
25 mg tablett én gang daglig i 96 uker

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
Tidsramme
Gjennomsnittlig endring fra baseline til uke 48 og uke 96 i absolutt og relativ CD4+-celletall (ved bruk av imputerte data)
Tidsramme: Baseline, uke 48 og uke 96
Endring fra baseline i CD4+-celletall ble imputert i tilfelle manglende verdier: i tilfelle for tidlig seponering ble data imputert med baseline-verdien etter seponering (dvs. change=0, Non-Completer [NC] = Failure); ellers ble siste observasjon overført.
Baseline, uke 48 og uke 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. juni 2008

Primær fullføring (Faktiske)

1. januar 2010

Studiet fullført (Faktiske)

1. februar 2012

Datoer for studieregistrering

Først innsendt

11. oktober 2007

Først innsendt som oppfylte QC-kriteriene

11. oktober 2007

Først lagt ut (Anslag)

15. oktober 2007

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

1. april 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

3. mars 2016

Sist bekreftet

1. mars 2016

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere