A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients

This study has been completed.
Sponsor:
Collaborator:
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000973
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012

November 2, 1999
March 29, 2012
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Complete list of historical versions of study NCT00000973 on ClinicalTrials.gov Archive Site
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A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients
Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii

To determine the manner in which pyrimethamine is metabolized and excreted in patients currently receiving zidovudine (AZT). An important goal of this measurement is to establish the optimal dose of pyrimethamine necessary to prevent the development of toxoplasmosis in AIDS patients or delay the subsequent return of toxoplasmic encephalitis.

Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.

Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.

Patients receive the study treatment for a total of 22 days. Patients are given an initial dose of pyrimethamine followed by a lower dose given as a single oral daily dose for 21 days. Patients continue to receive AZT at the dose prescribed prior to enrollment in the study. Patients receive leucovorin calcium once a day. Neither the leucovorin calcium nor the AZT are provided through the study.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
  • Toxoplasmosis, Cerebral
  • HIV Infections
  • Drug: Pyrimethamine
  • Drug: Leucovorin calcium
  • Drug: Zidovudine
Not Provided
Jacobson JM, Davidian M, Rainey PM, Hafner R, Raasch RH, Luft BJ. Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii. Antimicrob Agents Chemother. 1996 Jun;40(6):1360-5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
March 1995
Not Provided

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis.
  • Isoniazid not initiated during study period.
  • Methadone maintenance.

Required:

  • Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Prior history of toxoplasmic encephalitis.
  • Unable to take oral medication reliably or have a malabsorption syndrome (i.e., 3 or more loose stools/day for at least 4 weeks associated with an unintentional weight loss of = or > 10 percent of body weight).
  • History of sensitivity to the study medications.

Concurrent Medication:

Excluded:

  • Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy.
  • Medications such as aspirin, benzodiazepines, cimetidine, indomethacin, morphine, and sulfonamides should be avoided.

Concurrent Treatment:

Excluded:

  • Lymphocyte replacement.

Patients with the following are excluded:

  • Any medical or social condition that, in the opinion of the investigator, would adversely affect either participation or compliance in the study.
  • Diagnosis of AIDS and febrile and have evidence of another serious opportunistic infection or central nervous system impairment.

Prior Medication:

Excluded:

  • Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy within past 14 days.

Prior Treatment:

Excluded:

  • Lymphocyte replacement within past 14 days.

Patients have the following symptoms and conditions:

  • Laboratory evidence of HIV infection.
  • Serological evidence of exposure to Toxoplasma gondii, but no clinical evidence of active toxoplasmic infection.
  • Able to understand and sign a written informed consent.
  • Either homosexual male or intravenous drug user.

Required:

  • Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day for 4 weeks.

Intravenous drug abuse.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000973
ACTG 102, 11077
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Glaxo Wellcome
Study Chair: B Luft
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP