Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000773

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

To determine the safety, tolerance, and pharmacokinetics of a new improved microparticulate suspension formulation of atovaquone administered at one of two dose levels (per 09/30/94 amendment, a third dose level was added) daily for 12 days in HIV-infected and perinatally exposed (per 8/9/95 amendment) infants and children who are at risk of developing Pneumocystis carinii pneumonia (PCP).

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Atovaquone	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children

Actual Study Completion Date :

Sep 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Pediatric AIDS CRS	San Francisco	California	United States	94143
2	Chicago Children's CRS	Chicago	Illinois	United States	60614
3	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana	United States
4	DUMC Ped. CRS	Durham	North Carolina	United States
5	St. Jude/UTHSC CRS	Memphis	Tennessee	United States	38105
6	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan		Puerto Rico	00936