To determine the pharmacokinetic profile of single doses of letrazuril in patients with AIDS-related cryptosporidial diarrhea; to determine the dose proportionality of single escalating doses of letrazuril; to determine steady-state concentrations of letrazuril; to evaluate the safety and efficacy of escalating doses of letrazuril, compared with placebo, for patients with AIDS-related cryptosporidial diarrhea. Letrazuril, the p-fluor analog of diclazuril, has been shown in an animal model to prevent infections by organisms closely related to the intracellular parasite Cryptosporidium. Reliable data are needed to show the effectiveness of letrazuril in treating AIDS-related cryptosporidial diarrhea.

Condition	Treatment or Intervention	Phase
Cryptosporidiosis HIV Infections	Drug: Letrazuril	Phase I

Further Study Details: 

Expected Total Enrollment:  32

Letrazuril, the p-fluor analog of diclazuril, has been shown in an animal model to prevent infections by organisms closely related to the intracellular parasite Cryptosporidium. Reliable data are needed to show the effectiveness of letrazuril in treating AIDS-related cryptosporidial diarrhea.

Four groups of eight patients receive escalating doses of oral letrazuril (or placebo). In each group, six patients are randomized to receive letrazuril and two patients receive matching placebo. In the pharmacokinetics determination phase of the study, patients receive a single dose of letrazuril or placebo following a meal. Following a 72-hour blood collection, patients enter the blinded, treatment phase of the study and receive letrazuril or placebo as a single dose daily, after a meal, for 3 weeks. Patients with persistent Cryptosporidium oocysts in their stools at the end of the blinded treatment phase may continue with open-label treatment of letrazuril at the same dose for 4 weeks; the dose may subsequently be escalated every 4 weeks, to a maximum, if oocysts persist. Patients who have Cryptosporidium oocysts eradicated from their stools will discontinue treatment and be followed for 3 months. All patients undergo clinical follow-up at 3 and 6 months.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Anti-diarrheal and antiemetic medications.
• Anti-HIV agents such as zidovudine, ddI, and ddC if dosing regimens were stable for at least 3 weeks prior to start of study drug.

Patients must have:

• AIDS.
• Chronic diarrhea with presence of Cryptosporidium oocysts in a stool specimen.
• CD4 count < 150/mm3 (not required if patient has had cryptosporidiosis for a minimum of 4 weeks).
• Life expectancy of at least 1 month.

Prior Medication: Allowed:

• Anti-HIV agents such as zidovudine, ddI, and ddC if dosing regimens were stable for at least 3 weeks prior to start of study drug.
• Anti-diarrheal and antiemetic medications.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms or conditions are excluded:

• Grade 4 hematologic toxicity or grade 3 other toxicity ( patients with grade 3 hepatic toxicity may be enrolled if abnormalities are considered to be caused by biliary cryptosporidiosis).
• Presence of other diarrhea-causing pathogens.
• Active (defined as newly diagnosed, progressive, or requiring therapeutic intervention) opportunistic infection that requires antimicrobial therapy (patients receiving maintenance or prophylactic antimicrobial therapy for opportunistic infection may be enrolled if the dosing regimen has been stable for at least 3 weeks).
• Evidence of cytomegalovirus retinitis or colitis.

Concurrent Medication: Excluded:

• Ganciclovir, cancer chemotherapy, or interferon-alpha or other immunomodulating agents.
• Any investigational drug (drugs available under an FDA-authorized expanded access program will not be considered investigational).

Prior Medication: Excluded:

• Any investigational drug within 1 month prior to start of study drug (drugs available under an FDA-authorized expanded access program will not be considered investigational).
• Ganciclovir, cancer chemotherapy, or interferon-alpha or other immunomodulating agents within 7 days prior to start of study drug.

California
      USC School of Medicine, Los Angeles,  California,  90033,  United States
New York
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Dr Douglas Dieterich, New York,  New York,  10016,  United States

Study chairs or principal investigators

Moskovitz BL,  Study Chair

Study ID Numbers:  ACTG 198; Protocol JRD 65731/1001
Record last reviewed:  October 1992
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001018
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08