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

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
  • United States
    • California
      • San Francisco, California, United States, 94143
        • UCSF Pediatric AIDS CRS
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Chicago Children's CRS
    • Louisiana
      • New Orleans, Louisiana, United States
        • Tulane/LSU Maternal/Child CRS
    • North Carolina
      • Durham, North Carolina, United States
        • DUMC Ped. CRS
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude/UTHSC CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Hughes W
  • Study Chair: Dorenbaum A

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Dorenbaum A, Sadler BM, Xu J, Van Dyke RB, Wei LJ, Moye J, McNamara J, Yogev R, Diaz C, Hughes W. Phase I safety and pharmacokinetics (PK) study of micronized atovaquone (m-ATQ) in HIV exposed or infected infants and children. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:117 (abstract no 288)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

September 1, 1996

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

October 28, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 227
  • 11204 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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