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Completed

NCT Number: NCT00110305

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

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.

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Key information

Conditions

Human Immunodeficiency Virus Type 1 Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TMC278 25 mg

Drug

TMC278 25 mg tablet will be administered once daily.

TMC278 75 mg

Drug

TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.

TMC278 150 mg

Drug

TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.

Efavirenz

Drug

Efavirenz 600 mg (1 x 600 mg tablet or 3 x 200 mg capsules, depending on formulation locally available) will be administered once daily.

Non-nucleoside reverse transcriptase inhibitor (NRTIs)

Drug

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.

Other names: Combivir, Truvada

Primary outcomes

  1. 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

    Time frame: 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.

Secondary outcomes

  1. 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

    Time frame: 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.

  2. Number of Participants With Virologic Response at Week 96 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis

    Time frame: 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.

  3. 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

    Time frame: 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.

  4. Number of Participants With Virologic Response at Week 240 (Viral Load Less Than 50 Copies Per mL) - Snapshot Analysis

    Time frame: 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.

  5. 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

    Time frame: 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.

  6. Change From Baseline in CD4+ Cell Count (Absolute) at Week 96

    Time frame: 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.

  7. Change From Baseline in CD4+ Cell Count (Relative) at Week 96

    Time frame: 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.

  8. Change From Baseline in CD4+ Cell Count (Absolute) at Week 240

    Time frame: 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.

  9. Change From Baseline in CD4+ Cell Count (Relative) at Week 240

    Time frame: 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.

  10. Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure

    Time frame: 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).

  11. Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hours (AUC24h) for TMC278

    Time frame: 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.

  12. Trough Plasma Concentration (Ctrough) for TMC278

    Time frame: 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.

  13. 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Tibotec Pharmaceuticals, Ireland

Industry

Registry information

Official study title

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

Important dates

Study start
2005
Primary completion
2011
Study completion
2011
First posted
May 6, 2005
Registry last updated
Jun 25, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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