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An Efficacy Study of 2',3'-Dideoxyinosine (ddI) (BMY-40900) Administered Orally Twice Daily to Zidovudine Intolerant Patients With AIDS or AIDS-Related Complex

2011年3月11日 更新者：National Institute of Allergy and Infectious Diseases (NIAID)

AMENDED: 8/29/90 Inclusion of asymptomatic patients with CD4 counts less than 200 cells/mm3. Standardization of baseline evaluation schedule to allow 14 days prior to study dosing. Reduction in frequency and intensity of follow-up evaluations. Standardization of study endpoints. Inclusion of toxicity scoring and management for amylase and triglyceride elevations. Clarification of concomitant medication use. Original design: To determine the effectiveness of didanosine (ddI) in patients with AIDS or advanced AIDS related complex (ARC) who have documented hematologic intolerance to zidovudine (AZT) therapy. To determine if the efficacy of ddI increases with increasing doses.

AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication (reproduction) of HIV with less apparent toxicity than AZT. The major dose-limiting toxicities found in the Phase I studies have been pains in the feet and legs of 2 patients initially receiving 12 mg/kg/day and 12 patients receiving daily doses of 25.8 to 51.2 mg/kg; symptoms began 8 to 27 weeks after initiating ddI treatment. These neuropathy-like symptoms have generally not been associated with significant abnormalities in nerve conduction studies and patients have reported marked improvement in symptoms within 1 to 2 weeks of discontinuing ddI. Some patients have resumed ddI treatment at a reduced dose after resolution of their symptoms. Studies indicate that ddI remains active in the body for at least 12 hours. This indicates that benefits of ddI might be achieved with a low frequency of drug administration.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication (reproduction) of HIV with less apparent toxicity than AZT. The major dose-limiting toxicities found in the Phase I studies have been pains in the feet and legs of 2 patients initially receiving 12 mg/kg/day and 12 patients receiving daily doses of 25.8 to 51.2 mg/kg; symptoms began 8 to 27 weeks after initiating ddI treatment. These neuropathy-like symptoms have generally not been associated with significant abnormalities in nerve conduction studies and patients have reported marked improvement in symptoms within 1 to 2 weeks of discontinuing ddI. Some patients have resumed ddI treatment at a reduced dose after resolution of their symptoms. Studies indicate that ddI remains active in the body for at least 12 hours. This indicates that benefits of ddI might be achieved with a low frequency of drug administration.

Patients are randomized to one of three ddI treatment groups; within each group, doses will be adjusted according to patient's weight at study entry. Stratification is by diagnosis of AIDS or AIDS related complex (ARC) and Medical Center. Data will be tabulated for the Data and Safety Monitoring Board at 3 month intervals.

研究の種類

介入

入学

660

段階

  • フェーズ2

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
      • Los Angeles、California、アメリカ、90033
        • Los Angeles County - USC Med Ctr
      • Los Angeles、California、アメリカ、900481804
        • Cedars Sinai / UCLA Med Ctr
      • Los Angeles、California、アメリカ、905022004
        • Harbor - UCLA Med Ctr / UCLA School of Medicine
      • Los Angeles、California、アメリカ、900951752
        • UCLA Med Ctr / Pediatric
      • Palo Alto、California、アメリカ、94304
        • Palo Alto Veterans Adm Med Ctr / Stanford Univ
      • San Diego、California、アメリカ、921036325
        • Univ of California / San Diego Treatment Ctr
      • Stanford、California、アメリカ、94305
        • Stanford Univ School of Medicine
      • Sylmar、California、アメリカ、91342
        • Olive View Med Ctr
      • Sylmar、California、アメリカ、91342
        • Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr
      • Torrance、California、アメリカ、90502
        • Harbor UCLA Med Ctr
    • Colorado
      • Denver、Colorado、アメリカ、80262
        • Univ of Colorado Health Sciences Ctr
      • Denver、Colorado、アメリカ、80262
        • Mountain States Regional Hemophilia Ctr / Univ of Colorado
    • District of Columbia
      • Washington、District of Columbia、アメリカ、20037
        • George Washington Univ Med Ctr
    • Florida
      • Fort Lauderdale、Florida、アメリカ、33316
        • G E Morey Jr
      • Miami、Florida、アメリカ、331361013
        • Univ of Miami School of Medicine
      • Tampa、Florida、アメリカ、33612
        • Univ of South Florida
    • Illinois
      • Chicago、Illinois、アメリカ、60611
        • Northwestern Univ Med School
      • Hines、Illinois、アメリカ、60141
        • Edward Hines Veterans Administration Hosp
    • Indiana
      • Indianapolis、Indiana、アメリカ、462025250
        • Indiana Univ Hosp
    • Kansas
      • Wichita、Kansas、アメリカ、67214
        • Univ of Kansas School of Medicine
    • Louisiana
      • New Orleans、Louisiana、アメリカ、70112
        • Louisiana Comprehensive Hemophilia Care Ctr
      • New Orleans、Louisiana、アメリカ、70112
        • Louisiana State Univ Med Ctr / Tulane Med School
      • New Orleans、Louisiana、アメリカ、70112
        • Tulane Univ School of Medicine
    • Maryland
      • Baltimore、Maryland、アメリカ、21287
        • Johns Hopkins Hosp
    • Massachusetts
      • Boston、Massachusetts、アメリカ、02114
        • Harvard (Massachusetts Gen Hosp)
      • Boston、Massachusetts、アメリカ、02118
        • Boston Med Ctr
      • Boston、Massachusetts、アメリカ、02215
        • Beth Israel Deaconess - West Campus
      • Boston、Massachusetts、アメリカ、02215
        • Beth Israel Deaconess Med Ctr
      • Springfield、Massachusetts、アメリカ、01199
        • Baystate Med Ctr of Springfield
      • Worcester、Massachusetts、アメリカ、01605
        • Med Ctr of Central Massachusetts
      • Worcester、Massachusetts、アメリカ、01655
        • Univ of Massachusetts Med Ctr
    • Minnesota
      • Minneapolis、Minnesota、アメリカ、55455
        • Univ of Minnesota
    • Nebraska
      • Omaha、Nebraska、アメリカ、68105
        • Nebraska Regional Hemophilia Ctr
    • New York
      • Bronx、New York、アメリカ、10461
        • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
      • Bronx、New York、アメリカ、10465
        • Jack Weiler Hosp / Bronx Municipal Hosp
      • Bronx、New York、アメリカ、10467
        • Montefiore Med Ctr / Bronx Municipal Hosp
      • Bronx、New York、アメリカ、10468
        • Bronx Veterans Administration / Mount Sinai Hosp
      • Buffalo、New York、アメリカ、14215
        • SUNY / Erie County Med Ctr at Buffalo
      • Elmhurst、New York、アメリカ、11373
        • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
      • New York、New York、アメリカ、10003
        • Beth Israel Med Ctr / Peter Krueger Clinic
      • New York、New York、アメリカ、10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York、New York、アメリカ、10021
        • Mem Sloan - Kettering Cancer Ctr
      • New York、New York、アメリカ、10025
        • Saint Luke's - Roosevelt Hosp Ctr
      • New York、New York、アメリカ、10029
        • Mount Sinai Hemophilia Ctr / Mount Sinai Med Ctr
      • New York、New York、アメリカ、10029
        • Mount Sinai Med Ctr
      • Rochester、New York、アメリカ、14642
        • Univ of Rochester Medical Center
      • Stony Brook、New York、アメリカ、117948153
        • SUNY - Stony Brook
      • Syracuse、New York、アメリカ、13210
        • SUNY / State Univ of New York
    • North Carolina
      • Chapel Hill、North Carolina、アメリカ、275997215
        • Univ of North Carolina
      • Durham、North Carolina、アメリカ、27710
        • Duke Univ Med Ctr
      • Winston-Salem、North Carolina、アメリカ、27103
        • Bowman Gray School of Medicine / Wake Forest Univ
    • Ohio
      • Cincinnati、Ohio、アメリカ、452670405
        • Holmes Hosp / Univ of Cincinnati Med Ctr
      • Cleveland、Ohio、アメリカ、44106
        • Univ Hosp of Cleveland / Case Western Reserve Univ
      • Columbus、Ohio、アメリカ、432101228
        • Ohio State Univ Hosp Clinic
    • Pennsylvania
      • Hershey、Pennsylvania、アメリカ、170330850
        • Milton S Hershey Med Ctr
      • Philadelphia、Pennsylvania、アメリカ、19104
        • Univ of Pennsylvania
      • Pittsburgh、Pennsylvania、アメリカ、15219
        • Hemophilia Ctr of Western PA / Univ of Pittsburgh
      • Pittsburgh、Pennsylvania、アメリカ
        • Univ of Pittsburgh Med School
    • South Carolina
      • West Columbia、South Carolina、アメリカ、29169
        • Julio Arroyo
    • Tennessee
      • Knoxville、Tennessee、アメリカ、37920
        • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
    • Texas
      • Galveston、Texas、アメリカ、77550
        • Univ TX Galveston Med Branch
      • Houston、Texas、アメリカ、77030
        • Hermann Hosp / Univ Texas Health Science Ctr
      • Houston、Texas、アメリカ、77030
        • Texas Children's Hosp / Baylor Univ
    • Utah
      • Salt Lake City、Utah、アメリカ、84132
        • Univ of Utah School of Medicine
    • Washington
      • Seattle、Washington、アメリカ、98105
        • Univ of Washington
    • Wisconsin
      • Milwaukee、Wisconsin、アメリカ、53233
        • Great Lakes Hemophilia Foundation
  • プエルトリコ
      • San Juan、プエルトリコ、009275800
        • San Juan Veterans Administration Med Ctr

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

12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

Concurrent Medication:

Required:

  • Aerosolized pentamidine (300 mg every 4 weeks). In the event of physiological intolerance, alternative PCP prophylaxis may be trimethoprim/sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg per day.

Allowed:

  • Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus, cytomegalovirus, coccidioidomycosis, and histoplasmosis (absorption of ketoconazole or dapsone may be inhibited if given at the same time as the buffered solution of ddI, and should be taken 2 hours before or 2 hours after taking ddI; oral acidifying agents are not allowed). Isoniazid is permitted only if no acceptable alternative therapy is available. Metronidazole may be used for single courses not to exceed 14 days within consecutive 90 day intervals, the first of which begins at the initiation of the study. Erythropoietin for patients under the relevant treatment IND. Intravenous acyclovir for short courses of therapy.

Patients must:

  • Have documented hematologic intolerance to zidovudine (AZT).
  • Have the diagnosis of AIDS or advanced AIDS related complex (ARC).
  • Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks before study entry.

Have previous intolerance on at least two courses of AZT therapy (one of which must have been at daily doses of 500 mg of AZT or less).

  • Be able to provide informed consent (and/or guardian as appropriate).
  • Be available for follow-up for at least 6 months.
  • Have baseline laboratory values as measured within 7 days before initial drug dosing.
  • Allowed:
  • Development of new opportunistic infections during the study - patients remain in the protocol.

Prior Medication:

Required:

  • Prior use and intolerance to zidovudine (AZT).
  • Allowed:
  • Intralesional agents.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Presence of Kaposi's sarcoma (KS) with known or suspected visceral disease or where KS requires chemotherapy.
  • Active AIDS defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • Stage 2 AIDS-dementia complex.
  • History of intolerance to aerosolized pentamidine.
  • Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia.
  • Prior history of acute or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.

Concurrent Medication:

Excluded:

  • Isoniazid (INH).

Patients with the following are excluded:

  • Active AIDS-defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • AIDS-dementia complex = or > stage 2.
  • History of intolerance to aerosolized pentamidine. Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia.
  • Prior history of acute or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.
  • Previous participation in any Phase I ddI study.
  • Life expectancy < 6 months.

Prior Medication:

Excluded:

  • Chronic therapy for cytomegalovirus infection with ganciclovir.
  • ddI.
  • d4T.
  • ddC.

Excluded within 2 weeks of study entry:

  • Zidovudine (AZT).

Excluded within 1 month of study entry:

  • Therapy with any other antiretroviral drug or investigational agent not specifically allowed, including interferon and immunomodulating drugs.
  • Ganciclovir.
  • Neurotoxic drugs.

Excluded within 3 months of study entry:

  • Ribavirin.
  • Cytotoxic anticancer therapy.

Prior Treatment:

Excluded within 2 weeks of study randomization:

  • Transfusion.

Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.

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

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

National Institute of Allergy and Infectious Diseases (NIAID)

協力者

Bristol-Myers Squibb

捜査官

  • スタディチェア：JD Allan
  • スタディチェア：J Groopman
  • スタディチェア：M Seidlin

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

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

一次修了 (実際)

1993年2月1日

試験登録日

最初に提出

1999年11月2日

QC基準を満たした最初の提出物

2001年8月30日

最初の投稿 (見積もり)

2001年8月31日

学習記録の更新

投稿された最後の更新 (見積もり)

2011年3月14日

QC基準を満たした最後の更新が送信されました

2011年3月11日

最終確認日

1994年10月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • ACTG 118
  • 070V1
  • AI454-007

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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