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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 uppdaterad 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning

660

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

12 år och äldre (Barn, Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbetspartners

Bristol-Myers Squibb

Utredare

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

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Primärt slutförande (Faktisk)

1 februari 1993

Studieregistreringsdatum

Först inskickad

2 november 1999

Först inskickad som uppfyllde QC-kriterierna

30 augusti 2001

Första postat (Uppskatta)

31 augusti 2001

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

14 mars 2011

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

11 mars 2011

Senast verifierad

1 oktober 1994

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • ACTG 118
  • 070V1
  • AI454-007

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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