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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

2011년 3월 11일 업데이트: 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.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록

660

단계

  • 2 단계

연락처 및 위치

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

연구 장소

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

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

12년 이상 (어린이, 성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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.

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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Institute of Allergy and Infectious Diseases (NIAID)

협력자

Bristol-Myers Squibb

수사관

  • 연구 의자: JD Allan
  • 연구 의자: J Groopman
  • 연구 의자: M Seidlin

간행물 및 유용한 링크

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

일반 간행물

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

기본 완료 (실제)

1993년 2월 1일

연구 등록 날짜

최초 제출

1999년 11월 2일

QC 기준을 충족하는 최초 제출

2001년 8월 30일

처음 게시됨 (추정)

2001년 8월 31일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2011년 3월 14일

QC 기준을 충족하는 마지막 업데이트 제출

2011년 3월 11일

마지막으로 확인됨

1994년 10월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • ACTG 118
  • 070V1
  • AI454-007

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. .

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