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

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000973

Collaborator

Glaxo Wellcome (Industry)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Toxoplasmosis, Cerebral HIV Infections	Drug: Pyrimethamine Drug: Leucovorin calcium Drug: Zidovudine	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii

Actual Study Completion Date :

Mar 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.