Phase II Study on the Antiviral Activity and Safety of BILR 355 BS in HIV-1 Infected, NNRTI-treated Patients
Randomised, Double-blind, Placebo-controlled 7 Day Monotherapy Phase IIa Study to Evaluate the Antiviral Activity and Safety of Increasing Doses of Oral Administered RTV-boosted BILR 355 BS (75 mg and 150 mg Twice Daily) in HIV-1-infected, NNRTI-experienced Patients, Followed by 28 Day Combination Therapy With Tipranavir or Lopinavir Based HAART-regimen
調査の概要
研究の種類
入学
段階
- フェーズ2
連絡先と場所
研究場所
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Berlin、ドイツ
- Boehringer Ingelheim Investigational Site
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Bochum、ドイツ
- Boehringer Ingelheim Investigational Site
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Bonn、ドイツ
- Boehringer Ingelheim Investigational Site
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Erlangen、ドイツ
- Boehringer Ingelheim Investigational Site
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Frankfurt/Main、ドイツ
- Boehringer Ingelheim Investigational Site
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Hamburg、ドイツ
- Boehringer Ingelheim Investigational Site
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Hannover、ドイツ
- Boehringer Ingelheim Investigational Site
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Heidelberg、ドイツ
- Boehringer Ingelheim Investigational Site
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Mainz、ドイツ
- Boehringer Ingelheim Investigational Site
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Munchen、ドイツ
- Boehringer Ingelheim Investigational Site
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Ulm、ドイツ
- Boehringer Ingelheim Investigational Site
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation.
- HIV-1 infected males or females >= 18 years of age.
- History of NNRTI based HAART >= 8 weeks and at least one, but not more than 3 NNRTI-associated resistance mutations by current genotype
- TPV/r or LPV/r susceptible
- CD4+ T lymphocyte count >= 100 cells/?l.
7. HIV-1 viral load >= 2000 copies/mL at screening. 8. Karnofsky score >= 70 9. Based on the antiviral resistance profile of the patients virus, the investigator must be able to construct a background HAART treatment regimen (OBR) such that the patient will receive 3 effective ARV drugs, in addition to his study medication.
10. Acceptable screening laboratory values (Visit 1) that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if the following apply: Absolute neutrophil count (ANC) >750/mm3 Hemoglobin >= 10 g/dL Platelet count >99,000/mm3 AST, ALT , and alkaline phosphatase < 2.5xULN >= DAIDS Grade 1) Total bilirubin <2.5xULN Serum amylase <1.5xULN 11. Acceptable medical history, as assessed by the investigator, with chest x-ray results and ECG within 1 year of study participation.
12. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system 13. A prior AIDS defining event, excluding mycobacterial and invasive fungal infections, is acceptable as long as it has resolved or the subject has been on stable treatment (e.g. opportunistic infection) for at least 12 weeks before screening (Visit 1). Note that prior oral thrush, candida esophagitis and cutaneous candida is acceptable.
Exclusion Criteria:
- The following resistance mutations demonstrated at any time prior to starting trial therapy: V106A and/or Y188L
Female patients of child-bearing potential who:
have a positive serum pregnancy test at screening or during the study, are breast feeding, are planning to become pregnant, are not willing to use a barrier method of contraception.
- Active Hepatitis B or C disease defined as HBsAg positive or HCV RNA positive with AST/ALT > DAIDS Grade 1
- Acute/previous mycobacterial or invasive fungal infection requiring therapy or prophylaxis with drugs interfering with or significantly affected by the cytochrome P450 system
- Use of investigational medications within 30 days before study entry or during the trial.
- Use of concomitant drugs that may significantly reduce plasma levels of the study medications.
- Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).
- Patients currently treated with systemic ant-cancer chemotherapy
- Inability to adhere to the requirements of the protocol, including active substance abuse, as defined by the investigator.
- In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:ダブル
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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The primary endpoint will be reduction in plasma HIV-1 RNA from baseline to day 8, expressed in log10 copies/mm3.
時間枠:day 8
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day 8
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Virologic response at Day 8 and Day 35 using <400 copies/mL and 0.5, 1 and 1.5 log10 reduction in viral load from baseline
時間枠:up to week 5
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up to week 5
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Change from baseline in viral load at each visit
時間枠:up to week 9
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up to week 9
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Change from baseline in CD4+ cell counts at each visit
時間枠:up to week 9
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up to week 9
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Time averaged change from baseline in viral load through Days 8 and 35
時間枠:up to week 5
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up to week 5
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Number of reverse transcriptase (RT) mutations at baseline
時間枠:up to week 5
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up to week 5
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Number of NNRTI resistance-associated mutations at baseline (refer to Appendix 10.4)
時間枠:up to week 5
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up to week 5
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The presence of specific RT mutations (both in the list of NNRTI mutations and not in the list for exploratory purposes) at baseline
時間枠:up to week 5
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up to week 5
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The inhibitory quotient and minimum measured concentration of the analyte in plasma (Cmin)
時間枠:up to Day 8
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up to Day 8
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Exploration of mutations that emerge with exposure to BILR 355 BS to determine the effect on both viral load and IC50 fold change from reference
時間枠:up to week 5
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up to week 5
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Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 12 hours post-dose (AUC0-12h)
時間枠:up to week 5
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up to week 5
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Maximum measured concentration of the analyte in plasma (Cmax)
時間枠:up to week 5
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up to week 5
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Changes in total cholesterol, LDL, HDL and triglycerides from baseline to days 8 and 35
時間枠:up to week 9
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up to week 9
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Incidence of rash, hepatic events, and CNS adverse events
時間枠:up to week 9
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up to week 9
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Incidence of any adverse events (treatment related and unrelated)
時間枠:up to week 9
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up to week 9
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Incidence of laboratory test abnormalities
時間枠:up to week 9
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up to week 9
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Incidence of serious adverse events (including AIDS-defining events)
時間枠:up to week 9
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up to week 9
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Incidence of ≥ DAIDS 2 Grade elevation in ALT/AST
時間枠:up to week 9
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up to week 9
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Incidence of AEs leading to discontinuation from the study
時間枠:up to week 9
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up to week 9
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 1188.31
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