Terminé

A Phase I Safety and Pharmacokinetics Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Infants and Children With AIDS or Symptomatic HIV Infection

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Ce qui est testé

Didanosine

Médicament
Qui peut participer

HIV Infections

De 3 mois à 12 ans
Comment se déroule l'étude

Étude thérapeutique

Phase 1
Interventionnel

Résumé

Sponsor principalNational Institute of Allergy and Infectious Diseases (NIAID)
Dernière mise à jour : 26 août 2008
Issu d'une base de données validée par les autorités. Revendiquer cette étude

To determine the safety and maximum tolerated dose (MTD) of 2',3'-dideoxyinosine (ddI), given orally and intravenously, in infants and children with AIDS. The study also measures bloodstream and cerebrospinal fluid (CSF) levels of the administered drug, and provides a preliminary assessment of the effectiveness of ddI on HIV replication. AMENDED: Based on safety established in the first dosing phase of 52 weeks and long term dosing data in adults, the dosing period will be extended to 104 weeks. Original design: Information presently available indicates that ddI has high antiviral activity with less apparent toxicity than zidovudine (AZT) (the drug presently used to treat AIDS). AMENDED: Based on safety established in the first dosing phase of 52 weeks and long term dosing data in adults, the dosing period will be extended to 104 weeks. Original design: Information presently available indicates that ddI has high antiviral activity with less apparent toxicity than zidovudine (AZT) (the drug presently used to treat AIDS). AMENDED: Dosing will proceed for 104 weeks at each dose level. Original design: Five patients are treated at the initial dose level. Because ddI is not stable in the acid environment of the stomach, oral doses of ddI follow administration of an antacid. An alternative method of dosing is to mix the reconstituted ddI with an appropriate volume of Maalox TC or Mylanta II. In order to determine the MTD, successive groups of 5 patients enter the study at a higher dose level after 3 patients have experienced 3 weeks of dosing and significant toxicities have not developed. Patients are assigned to treatment groups in the order in which they are enrolled. Dosing proceeds for 16 weeks at each dose level. However, consideration is given to escalating patients entered at the lowest dose to the next dose level after 10 weeks of dosing. The dose escalation continues until toxicities requiring dose modifications are found in 2 of 5 in any group.

Titre officielA Phase I Safety and Pharmacokinetics Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Infants and Children With AIDS or Symptomatic HIV Infection 
Sponsor principalNational Institute of Allergy and Infectious Diseases (NIAID)
Dernière mise à jour : 26 août 2008
Issu d'une base de données validée par les autorités. Revendiquer cette étude

Protocole

Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.
Détails du design
25 participants à inclureNombre total de participants que l'essai clinique vise à recruter.
Traitement
Cette étude teste un ou plusieurs traitements pour évaluer leur efficacité contre une maladie ou un problème de santé spécifique. L'objectif est de voir si un nouveau médicament ou une thérapie fonctionne mieux, ou provoque moins d'effets secondaires que les options existantes.

Comment la nature du traitement est tenue confidentielle
Dans une étude en ouvert, tous les participants ainsi que les chercheurs savent quel traitement est administré. Ce type de protocole est utilisé lorsqu'il n'est pas nécessaire ou pas possible de masquer les traitements.

Autres méthodes de masquage
Simple aveugle
: les participants ignorent le traitement reçu, mais les chercheurs le connaissent.

Double aveugle
: ni les participants ni les chercheurs ne savent quel traitement est administré.

Triple aveugle
: Les participants, les chercheurs et les personnes qui analysent les résultats ne savent pas quel traitement est administré.

Quadruple aveugle
: Les participants, les chercheurs, les personnes qui analysent les résultats et les professionnels de santé en charge du suivi ne savent pas non plus quel traitement est administré.

Éligibilité

Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.
Conditions
Critères
Tout sexeLe sexe biologique des participants éligibles à s'inscrire.
De 3 mois à 12 ansTranche d'âge des participants éligibles à participer.
Volontaires sains non autorisésIndique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.
Conditions
Pathologie
HIV Infections
Critères

Inclusion Criteria Concurrent Medication: Allowed: * Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis if this drug is extended to children. * Acute therapy not exceeding 7 days with oral or intravenous acyclovir for herpes simplex infections. * Trimethoprim / sulfamethoxazole for Pneumocystis carinii infections during course of study at discretion of investigator after discussion with the sponsor. * Symptomatic therapy with analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy as deemed necessary by the principal investigator. Patients must have: * Diagnosis of AIDS as defined by CDC or meeting CDC P2 classification. * Patients must be free of opportunistic infection or other serious bacterial, fungal, or parasitic infection at time of entry into study. * Life expectancy \> 6 months. * Parent or guardian (and patient as applicable) able to give informed consent. * Available for follow-up for at least 6 months. * Allowed: Hemophilia. Exclusion Criteria Co-existing Condition: Children with the following are excluded: * Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP. * Intractable diarrhea. * No venous access. * History of seizures within previous 2 years or currently requiring anticonvulsants for control. * Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of \< 10 percent on echocardiogram. * Renal disease. * Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study. Concurrent Medication: Excluded: * Antiretroviral drugs. * Zidovudine (AZT). * AL 721. * Interferon. * Corticosteroids. * Immunomodulating drugs. * Other systemic investigation agent. * Ribavirin. * Rifampin, barbiturates, or any other potent inducer or inhibitor of drug-metabolizing enzymes. * Cytotoxic anticancer therapy. * H-2 blockers. * Intravenous ketoconazole. * Immunoglobulin preparations. Children with the following are excluded: * Chronic hematologic disorders unrelated to coagulation defects, hemoglobinopathies, or ITP. * Intractable diarrhea. * No venous access. * History of seizures within previous 2 years or currently requiring anticonvulsants for control. * Currently active heart disease as evidenced by a cardiac arrhythmia or other significant abnormality on routine electrocardiography (ECG) or shortening fraction of \< 10 percent on echocardiogram. * Renal disease. * Any other clinical condition that in the opinion of the investigator makes the patient unsuitable for study. * Renal disease. Prior Medication: Excluded: * Any prior therapy which in the opinion of the investigator would make the patient unsuitable for study. Excluded within 2 weeks of study entry: * Trimethoprim / sulfamethoxazole. Excluded within 1 month of study entry: * Study drug or other antiretroviral drug or systemic investigational agent. * Any agent known as a potent inducer or inhibitor of drug metabolizing enzymes. * H-2 blockers. * Ketoconazole. * Immunoglobulin preparations. Excluded within 3 months of study entry: * Ribavirin. Excluded: * Zidovudine (AZT) for \> 6 months. * Cytotoxic anticancer therapy. Prior Treatment: Excluded within 4 weeks of study entry: * Blood transfusion. * Lymphocyte transfusions for immune reconstitution. * Bone marrow transplant.



Centres d'étude

Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.
Cette étude comporte 5 sites
Suspendu
Univ of Alabama at BirminghamBirmingham, United StatesVoir le site
Suspendu
Univ of Miami School of MedicineMiami, United States
Suspendu
The Regional Medical Ctr, MemphisMemphis, United States
Suspendu
Baylor College of MedicineHouston, United States

Terminé5 Centres d'Étude