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Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV

2010年11月29日 更新者：Bristol-Myers Squibb

Phase III Open Label Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV

The purpose of this study is to learn how well atazanavir (ATV) works in combination with ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral load of treatment experienced subjects with human immunodeficiency virus (HIV). There is a comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.

調査の概要

状態

完了

条件

介入・治療

研究の種類

介入

入学 (実際)

571

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • San Francisco、California、アメリカ、94121
      • Torrance、California、アメリカ、90502
    • Colorado
      • Boulder、Colorado、アメリカ、80304
    • Florida
      • Altamonte Springs、Florida、アメリカ
      • Ft Lauderdale、Florida、アメリカ、33308
      • Ft Lauderdale、Florida、アメリカ、33306
      • Miami Beach、Florida、アメリカ、33160
      • Orlando、Florida、アメリカ、32801
    • Georgia
      • Decatur、Georgia、アメリカ
    • Hawaii
      • Honolulu、Hawaii、アメリカ、96816
    • Indiana
      • Boise、Indiana、アメリカ
    • Kansas
      • Wichita、Kansas、アメリカ、67214
    • Kentucky
      • Louisville、Kentucky、アメリカ、40202
    • Louisiana
      • New Orleans、Louisiana、アメリカ
    • Massachusetts
      • Brookline、Massachusetts、アメリカ
      • Fall River、Massachusetts、アメリカ、02720
    • New Jersey
      • East Orange、New Jersey、アメリカ
      • Newark、New Jersey、アメリカ、07103
    • New York
      • Buffalo、New York、アメリカ、14215
      • Manhasset、New York、アメリカ、11030
      • New York、New York、アメリカ、10019
      • Rochester、New York、アメリカ、14620
    • North Carolina
      • Huntersville、North Carolina、アメリカ、28078
      • Winston Salem、North Carolina、アメリカ、29203
      • Winston-Salem、North Carolina、アメリカ、27157
    • Ohio
      • Akron、Ohio、アメリカ
    • Texas
      • Dallas、Texas、アメリカ
      • Dallas、Texas、アメリカ、75246
      • Houston、Texas、アメリカ、77006

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

16年歳以上 (子、大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  • Virologic failure to 2 or more highly active antiretroviral therapy (HAART) regimens that, in total, have included at least one drug from all approved classes protease inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (PI, NNRTI, NRTI):

    1. Currently on a failing HAART regimen with 2 qualifying plasma viral load measurements (hospital/clinic value within 4 weeks of screening with viral load equivalent to =>1,000 c/mL on the Roche Amplicor[TM] and central lab measurements of =>1,000 c/mL (Roche Amplicor[TM]) within 4 weeks of randomization
    2. Cluster of Differentiation 4 (CD4) cell count =>50 cells/mm3 obtained within 4 weeks prior to randomization
  • =>16 years of age (or minimum age as determined by local regulations or as legal requirements dictate);
  • History of prior virologic response to at least one HAART regimen, defined as a 1.0 log10 decline or a decline in viral load to <400 c/mL by Roche Amplicor or <500 c/mL by Chiron Quantiplex branched DNA (bDNA) assay
  • Both females of child bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted disease, including human immunodeficiency virus (HIV). Other contraception in addition to barrier methods is permitted; interaction between atazanavir and oral contraceptives has not been studied.
  • Subjects must be able to provide written informed consent;
  • Subjects should be available for follow-up for a period of at least 48 weeks

  • Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:

    1. serum creatine <1.5 times the upper limit of normal (ULN)
    2. total serum lipase <1.4 times the ULN
    3. liver enzymes alanine aminotransferase (AST), aspartate aminotransferase (ALT) <3 times the ULN
    4. total serum bilirubin <1.5 times the ULN

Exclusion Criteria:

  • Prior use (=>3 days) of atazanavir, TVF or LPV/RTV; if history of SQV, then must be phenotypically sensitive
  • the current failing antiretroviral regimen must have been administered for at least eight weeks at he initiation of screening and must not include both a PI and NNRTI
  • Presence of a newly diagnosed HIV-related opportunistic infection or any medical requiring acute therapy at the time of enrollment
  • Proven or suspected acute hepatitis in the 30 days prior to study entry. Subjects with chronic hepatitis are eligible provided that their liver function enzymes (ALT/AST) are <3 x ULN
  • Previous therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatoxic, hepatoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment of therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect Cytochrome P450 3A4 (CYP3A4).
  • Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis
  • Intractable diarrhea (=> 6 loose stools/day for at least 7 days consecutive days) within 30 days prior to study entry
  • Pregnancy or breast-feeding
  • History of hemophilia
  • Presence of cardiomyopathy

  • Any one of the following:

    1. Heart rate-corrected QT (QTc) interval >450 msec on the screening electrocardiogram (EKG)
    2. Heart rate <40 beats per minute (bpm)
    3. Pause length >3 seconds seen on EKG
    4. Clinical symptoms potentially related to heart block
    5. Third degree heart block
  • History of acute or chronic pancreatitis
  • If choosing 2'-3' dideoxyinosine (ddI) or 2',3'-didehydro-3'-deoxythymidine (d4T) as the NRTI: History or signs and symptoms of bilateral peripheral neuropathy => Grade 2 at the time of screening
  • Inability to tolerate oral medications
  • Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for study or unable to comply with the dosing requirements.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
アクティブコンパレータ：I

ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice

ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study
薬：Atazanavir + ritonavir + tenofovir + nucleoside
Active Comparator, Capsules, tablets, Oral
他の名前：
  • レヤタズ
  • BMS-232632
アクティブコンパレータ：II

ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice

ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study
薬：Atazanavir + saquinavir + tenofovir + nucleoside
Active Comparator, Capsules, tablets, Oral
他の名前：
  • レヤタズ
  • BMS-232632
アクティブコンパレータ：III

LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice

LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study
薬：Lopinavir/ritonavir + tenofovir + nucleoside
Active Comparator, Capsules, tablets, Oral

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
Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24
時間枠：Baseline, Week 24
Baseline, Week 24
Mean Change From Baseline in HIV RNA at Week 48
時間枠：Baseline, Week 48
Baseline, Week 48
Mean Change From Baseline in HIV RNA at Week 96
時間枠：Baseline, Week 96
Baseline, Week 96

二次結果の測定

結果測定
メジャーの説明
時間枠
24週目のCD4細胞数のベースラインからの変化
時間枠：ベースライン、24週目
ベースライン、24週目
48週目のCD4細胞数のベースラインからの変化
時間枠：ベースライン、48週目
ベースライン、48週目
96週目のCD4細胞数のベースラインからの変化
時間枠：ベースライン、96週
ベースライン、96週
Mean Change From Baseline in HIV RNA at Week 2
時間枠：Baseline, Week 2
Baseline, Week 2
Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity)
時間枠：Baseline, Week 24
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 400 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI.
Baseline, Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)
時間枠：Baseline, Week 48
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 400 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI.
Baseline, Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96
時間枠：Baseline, Week 96
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 400 c/mL at Week 96.
Baseline, Week 96
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24
時間枠：Week 24
Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity
時間枠：Baseline, Week 24
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 50 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI.
Baseline, Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48
時間枠：Week 48
Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity
時間枠：Baseline, Week 48
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 50 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI.
Baseline, Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96
時間枠：Week 96
Week 96
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24
時間枠：Week 24
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Week 24
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48
時間枠：Week 48
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Week 48
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96
時間枠：Week 96
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Week 96
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24
時間枠：Week 24
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Week 24
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48
時間枠：Week 48
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Week 48
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96
時間枠：Week 96
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Week 96
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24
時間枠：Baseline, Week 24
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 24 were explored.
Baseline, Week 24
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48
時間枠：Baseline, Week 48
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 48 were explored.
Baseline, Week 48
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24
時間枠：Baseline, Week 24
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 24 were explored.
Baseline, Week 24
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48
時間枠：Baseline, Week 48
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 48 were explored.
Baseline, Week 48
Lipid Mean Percent Change From Baseline at Week 24
時間枠：Baseline, Week 24
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Baseline, Week 24
Lipid Mean Percent Change From Baseline at Week 48
時間枠：Week 48
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Week 48
Lipid Mean Percent Change From Baseline at Week 96, Observed Values
時間枠：Week 96
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Week 96
Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48
時間枠：From Enrollment through Week 48
AE=any new untoward medical occurrence/worsening of a pre-existing medical condition regardless of causal relationship. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires/prolongs inpatient hospitalization; results in persistent/significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event.
From Enrollment through Week 48
Most Common AEs and AEs of Interest Through Week 48
時間枠：From Enrollment to Week 48
Prespecified AEs of interest included jaundice, ocular icterus, and hyperbilirubinemia.
From Enrollment to Week 48
Fasting Glucose Mean Change From Baseline at Week 24
時間枠：Baseline, Week 24
Baseline, Week 24
Fasting Glucose Mean Change From Baseline at Week 48
時間枠：Week 48
Week 48
Grade 3/4 Laboratory Abnormalities Through Week 48
時間枠：From Enrollment to Week 48
Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. Abnormal values: absolute neutrophil count: ≥500 to <750/mm3 (grade 3), <500/mm3 (grade 4); platelets: 20,000-49,999/mm3 (grade 3), <20,000/mm3 or diffuse petechiae (grade 4); alanine transaminase (ALT): 5.1-10 x upper limit of normal (ULN; grade 3), >10 x ULN (grade 4); aspartate transaminase (AST): 5.1-10 x ULN (grade 3), >10 x ULN (grade 4); bilirubin: 2.6-5 x ULN (grade 3), >5 x ULN (grade 4).
From Enrollment to Week 48
Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point
時間枠：Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QT interval was corrected for heart rate using Fridericia's (QTcF) formula.
Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
PR Interval and Change From Baseline by Analysis Time Point
時間枠：Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
The PR interval is measured from the beginning of the P wave to the beginning of the QRS complex, and reflects the time the electrical impulse takes to travel from the sinus node through the atrioventricular (AV) node and entering the ventricles. The PR interval is therefore a good estimate of AV node function.
Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire
時間枠：Baseline, Week 24, Week 48
The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Drug-specific questions included adherence with dose and frequency. Adherence was defined as taking all doses and numbers of pills as prescribed for each medication. This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Baseline, Week 24, Week 48
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)
時間枠：Baseline, Week 24, Week 48
The EQ-5D is a 5-item questionnaire to assess health-related quality of life in 5 health dimensions (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) are scored on a 3-level scale: no problems (1), some problems (2), extreme problems (3). Using a standard algorithm, responses are summarized into a single score, the EQ-5D Health Index Score (HIS), which ranges between 1 (representing perfect health) and 0 (representing the worst imaginable health state or death). The smallest coefficient of change is 0.03.
Baseline, Week 24, Week 48
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48)
時間枠：Baseline, Week 24, Week 48
The EQ-5D has a Visual Analog Scale (VAS), which is a feeling thermometer-like scale with a range between 0 and 100. Patients are required to draw a line from a box on the VAS scale to an actual mark on the thermometer-like scale that corresponds with a number that reflects their self-assessed health status at the time they are completing the questionnaire. Higher VAS scores indicate better overall health. There is no minimum clinically important difference reported in the literature for VAS.
Baseline, Week 24, Week 48
Number of Participants Utilizing Resources for Managing Lipid Elevation
時間枠：Baseline, Week 24, Week 48
Participants' overall resource utilization for managing lipid elevation that includes the management of side effects of lipid lowering medications, such as those due to drug interactions.
Baseline, Week 24, Week 48
Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values
時間枠：collected at the pre-dose time point after receiving atazanavir for at least four weeks
The minimum or "trough" concentration (Cmin) of a drug observed after its administration and just prior to the administration of a subsequent dose.
collected at the pre-dose time point after receiving atazanavir for at least four weeks
HIV IC50 at Week 24
時間枠：Week 24
IC50: inhibitory concentration of drug required to reduce viral replication by 50%.
Week 24
Inhibitory Quotient at Week 24
時間枠：Baseline, Week 24
Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50.
Baseline, Week 24
Inhibitory Quotient at Week 48
時間枠：Baseline, Week 48
Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50.
Baseline, Week 48
HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24
時間枠：Baseline, Week 24
Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins.
Baseline, Week 24
HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48
時間枠：Baseline, Week 48
Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins.
Baseline, Week 48

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Bristol-Myers Squibb

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2001年11月1日

一次修了 (実際)

2003年7月1日

研究の完了 (実際)

2009年3月1日

試験登録日

最初に提出

2002年5月6日

QC基準を満たした最初の提出物

2002年5月7日

最初の投稿 (見積もり)

2002年5月8日

学習記録の更新

投稿された最後の更新 (見積もり)

2010年12月24日

QC基準を満たした最後の更新が送信されました

2010年11月29日

最終確認日

2010年11月1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

  • AI424-045

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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