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- Klinische proef NCT00110305
A Study of TMC278 in Human Immunodeficiency Virus Type 1 Infected Patients, Who Are Not Treated With Antiretroviral Medicines
11 juni 2014 bijgewerkt door: 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.
Studie Overzicht
Toestand
Voltooid
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
368
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Buenos Aires, Argentinië
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Rosario, Argentinië
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Campinas, Brazilië
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Curitiba, Brazilië
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Pinheiros, Brazilië
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Rio De Janeiro, Brazilië
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Sao Paulo, Brazilië
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Beijing, China
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Berlin, Duitsland
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Freiburg, Duitsland
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Köln, Duitsland
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München, Duitsland
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Paris, Frankrijk
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Paris Cedex 10, Frankrijk
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Paris Cedex 12, Frankrijk
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Tourcoing, Frankrijk
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Ciudad De Mexico, Mexico
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Kampala, Oeganda
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Wien, Oostenrijk
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San Juan, Puerto Rico
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Kazan, Russische Federatie
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Moscow, Russische Federatie
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Moscow N/A, Russische Federatie
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Nizhny Novgorod, Russische Federatie
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Saint-Petersburg, Russische Federatie
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St Petersburg, Russische Federatie
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Volgograd, Russische Federatie
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Bangkok, Thailand
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Chiang Mai, Thailand
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Khon Kaen, Thailand
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London, Verenigd Koninkrijk
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Manchester, Verenigd Koninkrijk
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California
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Beverly Hills, California, Verenigde Staten
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District of Columbia
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Washington, District of Columbia, Verenigde Staten
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Florida
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Orlando, Florida, Verenigde Staten
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Tampa, Florida, Verenigde Staten
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Georgia
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Atlanta, Georgia, Verenigde Staten
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New York
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Stony Brook, New York, Verenigde Staten
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North Carolina
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Winston-Salem, North Carolina, Verenigde Staten
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Texas
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Addison, Texas, Verenigde Staten
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Washington
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Seattle, Washington, Verenigde Staten
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Bloemfontein, Zuid-Afrika
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Cape Town, Zuid-Afrika
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Johannesburg, Zuid-Afrika
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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.
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TMC278 25 mg tablet will be administered once daily.
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:
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Experimenteel: 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.
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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:
TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.
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Experimenteel: 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.
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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:
TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.
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Actieve vergelijker: 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.
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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:
Efavirenz 600 mg (1 x 600 mg tablet or 3 x 200 mg capsules, depending on formulation locally available) will be administered once daily.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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
Tijdsspanne: Week 48
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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.
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Week 48
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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
Tijdsspanne: Week 96
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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.
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Week 96
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Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Tijdsspanne: Week 96
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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.
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Week 96
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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
Tijdsspanne: Week 240
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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.
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Week 240
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Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis
Tijdsspanne: Week 240
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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.
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Week 240
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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
Tijdsspanne: Week 240
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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.
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Week 240
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Change From Baseline in CD4+ Cell Count (Absolute) at Week 96
Tijdsspanne: Baseline (Day 1 of Week 0) to Week 96
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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.
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Baseline (Day 1 of Week 0) to Week 96
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Change From Baseline in CD4+ Cell Count (Relative) at Week 96
Tijdsspanne: Baseline (Day 1 of Week 0) to Week 96
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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.
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Baseline (Day 1 of Week 0) to Week 96
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Change From Baseline in CD4+ Cell Count (Absolute) at Week 240
Tijdsspanne: Baseline (Day 1 of Week 0) to Week 240
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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.
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Baseline (Day 1 of Week 0) to Week 240
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Change From Baseline in CD4+ Cell Count (Relative) at Week 240
Tijdsspanne: Baseline (Day 1 of week 0) to Week 240
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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.
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Baseline (Day 1 of week 0) to Week 240
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Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
Tijdsspanne: Week 240
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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).
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Week 240
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Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278
Tijdsspanne: Up to Week 96
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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.
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Up to Week 96
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Trough Plasma Concentration (Ctrough) for TMC278
Tijdsspanne: Up to Week 96
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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.
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Up to Week 96
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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
Tijdsspanne: Up to Week 96
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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.
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Up to Week 96
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 juni 2005
Primaire voltooiing (Werkelijk)
1 december 2011
Studie voltooiing (Werkelijk)
1 december 2011
Studieregistratiedata
Eerst ingediend
5 mei 2005
Eerst ingediend dat voldeed aan de QC-criteria
5 mei 2005
Eerst geplaatst (Schatting)
6 mei 2005
Updates van studierecords
Laatste update geplaatst (Schatting)
25 juni 2014
Laatste update ingediend die voldeed aan QC-criteria
11 juni 2014
Laatst geverifieerd
1 juni 2014
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- RNA-virusinfecties
- Virusziekten
- Infecties
- Door bloed overgedragen infecties
- Overdraagbare ziekten
- Seksueel overdraagbare aandoeningen, viraal
- Seksueel overdraagbare aandoeningen
- Lentivirus-infecties
- Retroviridae-infecties
- Ziekten van het immuunsysteem
- Langzame virusziekten
- HIV-infecties
- Verworven Immunodeficiëntie Syndroom
- Immunologische deficiëntie syndromen
- Moleculaire mechanismen van farmacologische werking
- Anti-infectieuze middelen
- Antivirale middelen
- Nucleïnezuursyntheseremmers
- Enzymremmers
- Anti-hiv-middelen
- Antiretrovirale middelen
- Cytochroom P-450 enzymremmers
- Cytochroom P-450 enzyminductoren
- Cytochroom P-450 CYP3A-inductoren
- Cytochroom P-450 CYP2B6-inductoren
- Cytochroom P-450 CYP2C9-remmers
- Cytochroom P-450 CYP2C19-remmers
- Reverse Transcriptase-remmers
- Efavirenz
- Rilpivirine
Andere studie-ID-nummers
- CR006760
- TMC278-C204 (Andere identificatie: Tibotec Pharmaceuticals, Ireland)
- R278474-C204 (Andere identificatie: Tibotec Pharmaceuticals, Ireland)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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