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History of Changes for Study: NCT00000773
Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children.
Latest version (submitted October 27, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 23, 2005 None (earliest Version on record)
2 January 25, 2006 Study Identification and Study Status
3 March 30, 2012 Contacts/Locations, Study Status, Sponsor/Collaborators and Study Identification
4 October 27, 2021 Study Status and Study Identification
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Study NCT00000773
Submitted Date:  June 23, 2005 (v1)

Open or close this module Study Identification
Unique Protocol ID: ACTG 227
Brief Title: Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children.
Official Title: Phase I Safety and Pharmacokinetics Study of Microparticulate Atovaquone (m-Atovaquone; 566C80) in HIV-Infected and Perinatally Exposed Infants and Children.
Secondary IDs:
Open or close this module Study Status
Record Verification: June 1996
Overall Status: Completed
Study Start:
Primary Completion:
Study Completion:
First Submitted: November 2, 1999
First Submitted that
Met QC Criteria:
August 30, 2001
First Posted: August 31, 2001 [Estimate]
Last Update Submitted that
Met QC Criteria:
June 23, 2005
Last Update Posted: June 24, 2005 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible Party:
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:
Open or close this module 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.

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.

Open or close this module Conditions
Conditions: Pneumonia, Pneumocystis Carinii
HIV Infections
Keywords: Pneumonia, Pneumocystis carinii
Antifungal Agents
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Biological Availability
atovaquone
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Prevention
Study Phase: Phase 1
Interventional Study Model:
Number of Arms:
Masking: None (Open Label)
Enrollment: 24
Open or close this module Arms and Interventions
Intervention Details:
Drug: Atovaquone
Open or close this module Outcome Measures
Open or close this module Eligibility
Minimum Age: 1 Month
Maximum Age: 12 Years
Sex: All
Gender Based:
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.
Open or close this module Contacts/Locations
Study Officials: Hughes W
Study Chair
Dorenbaum A
Study Chair
Locations: United States, California
UCSF / Moffitt Hosp - Pediatric
San Francisco, California, United States, 941430105
United States, Illinois
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
United States, Tennessee
Saint Jude Children's Research Hosp of Memphis
Memphis, Tennessee, United States, 381052794
Puerto Rico
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, Puerto Rico, 009365067
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations: 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)
Links:
Available IPD/Information:

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