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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 aktualisiert von: 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.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

368

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Argentinien
      • Buenos Aires, Argentinien
      • Rosario, Argentinien
  • Brasilien
      • Campinas, Brasilien
      • Curitiba, Brasilien
      • Pinheiros, Brasilien
      • Rio De Janeiro, Brasilien
      • Sao Paulo, Brasilien
  • China
      • Beijing, China
  • Deutschland
      • Berlin, Deutschland
      • Freiburg, Deutschland
      • Köln, Deutschland
      • München, Deutschland
  • Frankreich
      • Paris, Frankreich
      • Paris Cedex 10, Frankreich
      • Paris Cedex 12, Frankreich
      • Tourcoing, Frankreich
  • Mexiko
      • Ciudad De Mexico, Mexiko
  • Puerto Rico
      • San Juan, Puerto Rico
  • Russische Föderation
      • Kazan, Russische Föderation
      • Moscow, Russische Föderation
      • Moscow N/A, Russische Föderation
      • Nizhny Novgorod, Russische Föderation
      • Saint-Petersburg, Russische Föderation
      • St Petersburg, Russische Föderation
      • Volgograd, Russische Föderation
  • Südafrika
      • Bloemfontein, Südafrika
      • Cape Town, Südafrika
      • Johannesburg, Südafrika
  • Thailand
      • Bangkok, Thailand
      • Chiang Mai, Thailand
      • Khon Kaen, Thailand
  • Uganda
      • Kampala, Uganda
  • Vereinigte Staaten
    • California
      • Beverly Hills, California, Vereinigte Staaten
    • District of Columbia
      • Washington, District of Columbia, Vereinigte Staaten
    • Florida
      • Orlando, Florida, Vereinigte Staaten
      • Tampa, Florida, Vereinigte Staaten
    • Georgia
      • Atlanta, Georgia, Vereinigte Staaten
    • New York
      • Stony Brook, New York, Vereinigte Staaten
    • North Carolina
      • Winston-Salem, North Carolina, Vereinigte Staaten
    • Texas
      • Addison, Texas, Vereinigte Staaten
    • Washington
      • Seattle, Washington, Vereinigte Staaten
  • Vereinigtes Königreich
      • London, Vereinigtes Königreich
      • Manchester, Vereinigtes Königreich
  • Österreich
      • Wien, Österreich

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Arzneimittel: TMC278 25 mg
TMC278 25 mg tablet will be administered once daily.
Arzneimittel: 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.
Andere Namen:
  • Truvada
  • Combivir
Experimental: 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.
Arzneimittel: 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.
Andere Namen:
  • Truvada
  • Combivir
Arzneimittel: TMC278 75 mg
TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.
Experimental: 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.
Arzneimittel: 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.
Andere Namen:
  • Truvada
  • Combivir
Arzneimittel: TMC278 150 mg
TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.
Aktiver 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.
Arzneimittel: 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.
Andere Namen:
  • Truvada
  • Combivir
Arzneimittel: 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.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
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
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Juni 2005

Primärer Abschluss (Tatsächlich)

1. Dezember 2011

Studienabschluss (Tatsächlich)

1. Dezember 2011

Studienanmeldedaten

Zuerst eingereicht

5. Mai 2005

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

5. Mai 2005

Zuerst gepostet (Schätzen)

6. Mai 2005

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

25. Juni 2014

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

11. Juni 2014

Zuletzt verifiziert

1. Juni 2014

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • CR006760
  • TMC278-C204 (Andere Kennung: Tibotec Pharmaceuticals, Ireland)
  • R278474-C204 (Andere Kennung: Tibotec Pharmaceuticals, Ireland)

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