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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000773
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Atovaquone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 24
Study Completion Date: September 1996
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.

  Eligibility

Ages Eligible for Study:   1 Month to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000773

Locations
United States, California
UCSF Pediatric AIDS CRS
San Francisco, California, United States, 94143
United States, Illinois
Chicago Children's CRS
Chicago, Illinois, United States, 60614
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 38105
Puerto Rico
Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Investigators
Study Chair: Hughes W
Study Chair: Dorenbaum A
  More Information

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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000773     History of Changes
Other Study ID Numbers: ACTG 227, 11204
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pneumonia, Pneumocystis carinii
Antifungal Agents
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Biological Availability
atovaquone

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Atovaquone
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014