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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 marca 2011 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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 studiów

Interwencyjne

Zapisy

660

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

12 lat i starsze (Dziecko, Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Współpracownicy

Bristol-Myers Squibb

Śledczy

  • Krzesło do nauki: JD Allan
  • Krzesło do nauki: J Groopman
  • Krzesło do nauki: M Seidlin

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Zakończenie podstawowe (Rzeczywisty)

1 lutego 1993

Daty rejestracji na studia

Pierwszy przesłany

2 listopada 1999

Pierwszy przesłany, który spełnia kryteria kontroli jakości

30 sierpnia 2001

Pierwszy wysłany (Oszacować)

31 sierpnia 2001

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

14 marca 2011

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

11 marca 2011

Ostatnia weryfikacja

1 października 1994

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • ACTG 118
  • 070V1
  • AI454-007

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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