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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

11. března 2011 aktualizováno: 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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis

660

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

12 let a starší (Dítě, Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

National Institute of Allergy and Infectious Diseases (NIAID)

Spolupracovníci

Bristol-Myers Squibb

Vyšetřovatelé

  • Studijní židle: JD Allan
  • Studijní židle: J Groopman
  • Studijní židle: M Seidlin

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Primární dokončení (Aktuální)

1. února 1993

Termíny zápisu do studia

První předloženo

2. listopadu 1999

První předloženo, které splnilo kritéria kontroly kvality

30. srpna 2001

První zveřejněno (Odhad)

31. srpna 2001

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

14. března 2011

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

11. března 2011

Naposledy ověřeno

1. října 1994

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • ACTG 118
  • 070V1
  • AI454-007

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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