Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children
Atovaquone
Blood-Borne Infections+23
+ Urogenital Diseases
+ Genital Diseases
Prevention Study
Summary
Atovaquone has shown prophylactic potential in adults in the treatment of PCP but is poorly absorbed in tablet form. To improve the bioavailability of atovaquone, a new formulation has been prepared as a microparticulate suspension. Since studies in adults have demonstrated substantial safety of this drug, evaluation in children is being pursued. Three cohorts of four patients each (ages 2-12 years, 3 months to less than 2 years, and 1 month to less than 3 months) receive atovaquone daily for 12 days. The oldest age group is treated first. In the absence of unacceptable toxicity, the dose of atovaquone is escalated in subsequent 4-patient cohorts representing each of the age stratifications and (per 9/30/94 amendment) in a separate 4-patient cohort aged 3 months to less than 2 years. If two of four patients in a given cohort experience unacceptable toxicity at the initial dose, two additional patients in the same age range are entered. Blood samples are drawn for pharmacokinetic evaluation. Patients are followed to day 24. Per 9/30/94 amendment, patients aged 3 months to less than 2 years of age who received one of the lower doses may re-enroll in the higher dose cohort after a 1-month washout.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.24 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Prevention Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 1 Months to 12 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT). Dideoxycytidine (zalcitabine; ddC). Didanosine (ddI). Nonaminoglycoside, nonmacrolide, and nonsulfonamide antibiotics. Factor VIII. IVIG. Patients must have: AIDS, documented HIV infection, perinatal exposure to HIV, or risk of developing PCP. Normal EKG and chest radiograph. No blood or protein on urinalysis. Consent of parent or guardian. Prior Medication: Allowed: Prophylactic TMP/SMX if given no less than 3 days prior to study entry. Prophylactic aerosolized pentamidine (or a single intravenous dose of 4.0 mg/kg pentamidine) if given no less than 7 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Anticipated organ system or laboratory abnormalities (other than immune system abnormalities) from the primary disease and its treatment during the study. Acute or chronic infections requiring treatment during the study. NOTE: Thrush and herpes labialis are allowed if these conditions do not require treatment. Diarrhea or vomiting. Concurrent Medication: Excluded: Trimethoprim/sulfamethoxazole. Sulfadoxine and pyrimethamine (Fansidar). Primaquine. Aspirin. Amphotericin B. Aminoglycoside antibiotics. Sulfonamides. Dapsone. Benzodiazepines. Rifampin. Erythromycin, clarithromycin, and azithromycin. Digitalis. Para-aminosalicylic acid (PAS). Isoniazid. Anticoagulants. Any other investigational therapies. Patients with the following prior condition are excluded: History of G6PD deficiency.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 6 locations
Chicago Children's CRS
Chicago, United StatesTulane/LSU Maternal/Child CRS
New Orleans, United StatesDUMC Ped. CRS
Durham, United States