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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. mars 2011 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering

660

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

12 år og eldre (Barn, Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbeidspartnere

Bristol-Myers Squibb

Etterforskere

  • Studiestol: JD Allan
  • Studiestol: J Groopman
  • Studiestol: M Seidlin

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Primær fullføring (Faktiske)

1. februar 1993

Datoer for studieregistrering

Først innsendt

2. november 1999

Først innsendt som oppfylte QC-kriteriene

30. august 2001

Først lagt ut (Anslag)

31. august 2001

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

14. mars 2011

Siste oppdatering sendt inn som oppfylte QC-kriteriene

11. mars 2011

Sist bekreftet

1. oktober 1994

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ACTG 118
  • 070V1
  • AI454-007

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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