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A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines

11. juni 2014 opdateret af: Tibotec Pharmaceuticals, Ireland

A Phase IIb Randomized, Partially Blinded, Dose-Finding Trial of TMC278 in Antiretroviral-Naive HIV-1 Infected Subjects

The purpose of this study is to evaluate the dose-response relationship of antiviral activity after 48 weeks treatment with 3 different dose regimens of TMC278.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This is a randomized (the study medication is assigned by chance), active controlled (participants are assigned to either a recognized effective treatment or the study medication) study. This study consists of 3 phases: screening phase (4 weeks), treatment phase (96 weeks), and follow up phase (4 weeks). In the treatment phase, participants will be randomly assigned to 1 of the 4 treatment groups: (1) TMC278 25 mg, (2) TMC278 75 mg, (3) TMC278 150 mg, or (4) efavirnez (control group); along with investigator selected 2 non-nucleoside reverse transcriptase inhibitor (NRTIs) until Week 96. TMC278 will be assigned by double-blinded fashion (participant and investigator are not aware of the TMC278 dose what participants will receive) and efavirnez will be assigned by open-label fashion (all people know what treatment participants will receive). After Week 96, 3 optional open-label (all people know the identity of the intervention) extension periods will be conducted to collect long term safety and effectiveness data of TMC278. 3 optional extension periods are: first optional extension period (all participants will receive TMC278 75 mg + 2 NRTIs from Week 96 to Week144); second optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 144 to Week 240); and third optional extension period (all participants will receive TMC278 25 mg + 2 NRTIs from Week 240 until TMC278 is commercially available). Participants on efavirenz group will have the option to continue on efavirenz + 2 NRTIs until the total treatment duration of 240 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, physical examination, and vital signs which will be monitored throughout the study. The maximum duration of the study will be 104, 152, or 248 weeks, plus the optional third extension period.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

368

Fase

  • Fase 2

Kontakter og lokationer

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

Studiesteder

  • Argentina
      • Buenos Aires, Argentina
      • Rosario, Argentina
  • Brasilien
      • Campinas, Brasilien
      • Curitiba, Brasilien
      • Pinheiros, Brasilien
      • Rio De Janeiro, Brasilien
      • Sao Paulo, Brasilien
  • Den Russiske Føderation
      • Kazan, Den Russiske Føderation
      • Moscow, Den Russiske Føderation
      • Moscow N/A, Den Russiske Føderation
      • Nizhny Novgorod, Den Russiske Føderation
      • Saint-Petersburg, Den Russiske Føderation
      • St Petersburg, Den Russiske Føderation
      • Volgograd, Den Russiske Føderation
  • Det Forenede Kongerige
      • London, Det Forenede Kongerige
      • Manchester, Det Forenede Kongerige
  • Forenede Stater
    • California
      • Beverly Hills, California, Forenede Stater
    • District of Columbia
      • Washington, District of Columbia, Forenede Stater
    • Florida
      • Orlando, Florida, Forenede Stater
      • Tampa, Florida, Forenede Stater
    • Georgia
      • Atlanta, Georgia, Forenede Stater
    • New York
      • Stony Brook, New York, Forenede Stater
    • North Carolina
      • Winston-Salem, North Carolina, Forenede Stater
    • Texas
      • Addison, Texas, Forenede Stater
    • Washington
      • Seattle, Washington, Forenede Stater
  • Frankrig
      • Paris, Frankrig
      • Paris Cedex 10, Frankrig
      • Paris Cedex 12, Frankrig
      • Tourcoing, Frankrig
  • Kina
      • Beijing, Kina
  • Mexico
      • Ciudad De Mexico, Mexico
  • Puerto Rico
      • San Juan, Puerto Rico
  • Sydafrika
      • Bloemfontein, Sydafrika
      • Cape Town, Sydafrika
      • Johannesburg, Sydafrika
  • Thailand
      • Bangkok, Thailand
      • Chiang Mai, Thailand
      • Khon Kaen, Thailand
  • Tyskland
      • Berlin, Tyskland
      • Freiburg, Tyskland
      • Köln, Tyskland
      • München, Tyskland
  • Uganda
      • Kampala, Uganda
  • Østrig
      • Wien, Østrig

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 og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Documented human immunodeficiency virus type 1 (HIV-1) infection
  • Never been treated with an antiretroviral (ARV) treatment or therapeutic HIV vaccine, or received less than or equal to 2 weeks treatment prior to screening with an nucleoside reverse transcriptase inhibitors
  • HIV-1 plasma viral load above 5000 HIV-1 RNA copies per milliliter, at screening
  • Cortisol of at least 550 nano moles per liter (19.9 microgram per deciliter) at screening
  • Sensitivity to investigator selected nucleosides, at screening

Exclusion Criteria:

  • Currently having active Acquired Immunodeficiency Syndrome (AIDS) defining illness
  • Known or suspected acute (primary) HIV-1 infection
  • Any current or history of adrenal disorder, and an acute hepatitis A, B, or C infection
  • Documented genotypic evidence of Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) resistance at screening
  • Pregnant or breastfeeding females
  • Not agree to protocol-defined effective use of contraception

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
Eksperimentel: TMC278 25 mg
Participants will receive TMC278 25 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.
Medicin: TMC278 25 mg
TMC278 25 mg tablet will be administered once daily.
Medicin: Non-nucleoside reverse transcriptase inhibitor (NRTIs)
Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.
Andre navne:
  • Truvada
  • Combivir
Eksperimentel: TMC278 75 mg
Participants will receive TMC278 75 mg once daily up to Week 144. Later on, participants will receive TMC278 25 mg once daily up to Week 240.
Medicin: Non-nucleoside reverse transcriptase inhibitor (NRTIs)
Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.
Andre navne:
  • Truvada
  • Combivir
Medicin: TMC278 75 mg
TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.
Eksperimentel: TMC278 150 mg
Participants will receive TMC278 150 mg once daily up to Week 96. Later on, participants will receive TMC278 75 mg once daily up to Week 144 and then TMC278 25 mg once daily up to Week 240.
Medicin: Non-nucleoside reverse transcriptase inhibitor (NRTIs)
Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.
Andre navne:
  • Truvada
  • Combivir
Medicin: TMC278 150 mg
TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.
Aktiv komparator: Efavirenz
Participants will receive efavirenz 600 mg once daily up to Week 96. Later on, participants will have an option to continue on efavirenz until Week 144 or until Week 240.
Medicin: Non-nucleoside reverse transcriptase inhibitor (NRTIs)
Investigator selected 2 NRTIs: (1) Zidovudine and lamivudine (Combivir) and (2) tenofovir disoproxil fumarate and emtricitabine (Truvada) will be administered as per the package inserts, along with the TMC278 during the study period.
Andre navne:
  • Truvada
  • Combivir
Medicin: Efavirenz
Efavirenz 600 mg (1 x 600 mg tablet or 3 x 200 mg capsules, depending on formulation locally available) will be administered once daily.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Virologic Response at Week 48 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Tidsramme: Week 48
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Week 48

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Tidsramme: Week 96
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Week 96
Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Tidsramme: Week 96
The analysis is based on the last observed viral load data within the Week 96 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.
Week 96
Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Tidsramme: Week 240
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Week 240
Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Tidsramme: Week 240
The analysis is based on the last observed viral load data within the Week 240 window. Virologic response is defined as a viral load less than 50 copies/mL. Missing viral load was considered as non-response.
Week 240
Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 400 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Tidsramme: Week 240
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Week 240
Change From Baseline in CD4+ Cell Count (Absolute) at Week 96
Tidsramme: Baseline (Day 1 of Week 0) to Week 96
Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Baseline (Day 1 of Week 0) to Week 96
Change From Baseline in CD4+ Cell Count (Relative) at Week 96
Tidsramme: Baseline (Day 1 of Week 0) to Week 96
Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Baseline (Day 1 of Week 0) to Week 96
Change From Baseline in CD4+ Cell Count (Absolute) at Week 240
Tidsramme: Baseline (Day 1 of Week 0) to Week 240
Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Baseline (Day 1 of Week 0) to Week 240
Change From Baseline in CD4+ Cell Count (Relative) at Week 240
Tidsramme: Baseline (Day 1 of week 0) to Week 240
Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer [NC] = Failure); otherwise last observation carried forward was applied.
Baseline (Day 1 of week 0) to Week 240
Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
Tidsramme: Week 240
Virologic failure for the resistance determinations was defined as a viral load greater than 0.5 log10 copies /mL above the nadir with a minimum of 500 copies/mL. For this study, treatment-emergent mutations (for at least one treatment) are presented as Resistance associated mutation (RAMs): i) Non-nucleotide reverse transcriptase inhibitor (NNRTI) RAMs, ii) Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Week 240
Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278
Tidsramme: Up to Week 96
For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96.
Up to Week 96
Trough Plasma Concentration (Ctrough) for TMC278
Tidsramme: Up to Week 96
For each participant, a single value for trough (i.e. predose) plasma concentration (Ctrough) of TMC278 was estimated from a population pharmacokinetic model, based on samples collected throughout the trial up to Week 96.
Up to Week 96
Number of Participants With Virologic Response (Viral Load Less Than 50 Copies Per mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm, by Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) Quartiles
Tidsramme: Up to Week 96
Quartile 1, 2, 3 and 4 of AUC24h means the quartile with the lowest 25%, 26-50%, 51-75% and the highest 25% of AUC24h values, respectively, irrespective of the different doses of TMC278. For each participant, a single value for area under the plasma concentration-time curve from time of administration up to 24 hours post dosing (AUC24h) of TMC278 was estimated from a population pharmacokinetic model, based on all samples collected throughout the trial up to Week 96. Virologic response was calculated by time to loss of virologic response (TLOVR) algorithm.
Up to 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 2005

Primær færdiggørelse (Faktiske)

1. december 2011

Studieafslutning (Faktiske)

1. december 2011

Datoer for studieregistrering

Først indsendt

5. maj 2005

Først indsendt, der opfyldte QC-kriterier

5. maj 2005

Først opslået (Skøn)

6. maj 2005

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

25. juni 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

11. juni 2014

Sidst verificeret

1. juni 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CR006760
  • TMC278-C204 (Anden identifikator: Tibotec Pharmaceuticals, Ireland)
  • R278474-C204 (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 .

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