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

11 июня 2014 г. обновлено: 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.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Подробное описание

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.

Тип исследования

Интервенционный

Регистрация (Действительный)

368

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Австрия
      • Wien, Австрия
  • Аргентина
      • Buenos Aires, Аргентина
      • Rosario, Аргентина
  • Бразилия
      • Campinas, Бразилия
      • Curitiba, Бразилия
      • Pinheiros, Бразилия
      • Rio De Janeiro, Бразилия
      • Sao Paulo, Бразилия
  • Германия
      • Berlin, Германия
      • Freiburg, Германия
      • Köln, Германия
      • München, Германия
  • Китай
      • Beijing, Китай
  • Мексика
      • Ciudad De Mexico, Мексика
  • Пуэрто-Рико
      • San Juan, Пуэрто-Рико
  • Российская Федерация
      • Kazan, Российская Федерация
      • Moscow, Российская Федерация
      • Moscow N/A, Российская Федерация
      • Nizhny Novgorod, Российская Федерация
      • Saint-Petersburg, Российская Федерация
      • St Petersburg, Российская Федерация
      • Volgograd, Российская Федерация
  • Соединенное Королевство
      • London, Соединенное Королевство
      • Manchester, Соединенное Королевство
  • Соединенные Штаты
    • California
      • Beverly Hills, California, Соединенные Штаты
    • District of Columbia
      • Washington, District of Columbia, Соединенные Штаты
    • Florida
      • Orlando, Florida, Соединенные Штаты
      • Tampa, Florida, Соединенные Штаты
    • Georgia
      • Atlanta, Georgia, Соединенные Штаты
    • New York
      • Stony Brook, New York, Соединенные Штаты
    • North Carolina
      • Winston-Salem, North Carolina, Соединенные Штаты
    • Texas
      • Addison, Texas, Соединенные Штаты
    • Washington
      • Seattle, Washington, Соединенные Штаты
  • Таиланд
      • Bangkok, Таиланд
      • Chiang Mai, Таиланд
      • Khon Kaen, Таиланд
  • Уганда
      • Kampala, Уганда
  • Франция
      • Paris, Франция
      • Paris Cedex 10, Франция
      • Paris Cedex 12, Франция
      • Tourcoing, Франция
  • Южная Африка
      • Bloemfontein, Южная Африка
      • Cape Town, Южная Африка
      • Johannesburg, Южная Африка

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Четырехместный

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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.
Лекарство: TMC278 25 mg
TMC278 25 mg tablet will be administered once daily.
Лекарство: 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.
Другие имена:
  • Трувада
  • Комбивир
Экспериментальный: 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.
Лекарство: 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.
Другие имена:
  • Трувада
  • Комбивир
Лекарство: TMC278 75 mg
TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.
Экспериментальный: 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.
Лекарство: 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.
Другие имена:
  • Трувада
  • Комбивир
Лекарство: TMC278 150 mg
TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.
Активный компаратор: 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.
Лекарство: 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.
Другие имена:
  • Трувада
  • Комбивир
Лекарство: 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.

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
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
Временное ограничение: 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

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Tibotec Pharmaceuticals, Ireland

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования

1 июня 2005 г.

Первичное завершение (Действительный)

1 декабря 2011 г.

Завершение исследования (Действительный)

1 декабря 2011 г.

Даты регистрации исследования

Первый отправленный

5 мая 2005 г.

Впервые представлено, что соответствует критериям контроля качества

5 мая 2005 г.

Первый опубликованный (Оценивать)

6 мая 2005 г.

Обновления учебных записей

Последнее опубликованное обновление (Оценивать)

25 июня 2014 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

11 июня 2014 г.

Последняя проверка

1 июня 2014 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • CR006760
  • TMC278-C204 (Другой идентификатор: Tibotec Pharmaceuticals, Ireland)
  • R278474-C204 (Другой идентификатор: Tibotec Pharmaceuticals, Ireland)

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

Клинические исследования TMC278 25 mg

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