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

2014년 6월 11일 업데이트: 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.

연구 개요

상세 설명

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.

연구 유형

중재적

등록 (실제)

368

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

      • Bloemfontein, 남아프리카
      • Cape Town, 남아프리카
      • Johannesburg, 남아프리카
      • Berlin, 독일
      • Freiburg, 독일
      • Köln, 독일
      • München, 독일
      • Kazan, 러시아 연방
      • Moscow, 러시아 연방
      • Moscow N/A, 러시아 연방
      • Nizhny Novgorod, 러시아 연방
      • Saint-Petersburg, 러시아 연방
      • St Petersburg, 러시아 연방
      • Volgograd, 러시아 연방
      • Ciudad De Mexico, 멕시코
    • California
      • Beverly Hills, California, 미국
    • District of Columbia
      • Washington, District of Columbia, 미국
    • Florida
      • Orlando, Florida, 미국
      • Tampa, Florida, 미국
    • Georgia
      • Atlanta, Georgia, 미국
    • New York
      • Stony Brook, New York, 미국
    • North Carolina
      • Winston-Salem, North Carolina, 미국
    • Texas
      • Addison, Texas, 미국
    • Washington
      • Seattle, Washington, 미국
      • Campinas, 브라질
      • Curitiba, 브라질
      • Pinheiros, 브라질
      • Rio De Janeiro, 브라질
      • Sao Paulo, 브라질
      • Buenos Aires, 아르헨티나
      • Rosario, 아르헨티나
      • London, 영국
      • Manchester, 영국
      • Wien, 오스트리아
      • Kampala, 우간다
      • Beijing, 중국
      • Bangkok, 태국
      • Chiang Mai, 태국
      • Khon Kaen, 태국
      • San Juan, 푸에르토 리코
      • Paris, 프랑스
      • Paris Cedex 10, 프랑스
      • Paris Cedex 12, 프랑스
      • Tourcoing, 프랑스

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 네 배로

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
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.
다른 이름들:
  • 트루바다
  • 콤비비르
실험적: 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.
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.
다른 이름들:
  • 트루바다
  • 콤비비르
TMC278 75 mg (1 X 25 mg + 1 X 50 mg) tablets will be administered once daily.
실험적: 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.
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.
다른 이름들:
  • 트루바다
  • 콤비비르
TMC278 150 mg (1 X 50 mg + 1 X 100 mg) tablets will be administered once daily.
활성 비교기: 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.
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.
다른 이름들:
  • 트루바다
  • 콤비비르
Efavirenz 600 mg (1 x 600 mg tablet or 3 x 200 mg capsules, depending on formulation locally available) will be administered once daily.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
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
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2005년 6월 1일

기본 완료 (실제)

2011년 12월 1일

연구 완료 (실제)

2011년 12월 1일

연구 등록 날짜

최초 제출

2005년 5월 5일

QC 기준을 충족하는 최초 제출

2005년 5월 5일

처음 게시됨 (추정)

2005년 5월 6일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2014년 6월 25일

QC 기준을 충족하는 마지막 업데이트 제출

2014년 6월 11일

마지막으로 확인됨

2014년 6월 1일

추가 정보

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다