A Study of Letrazuril in the Treatment of AIDS-Related Diarrhea

This study has been completed.
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001018
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: October 1992
  Purpose

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 Intervention Phase
Cryptosporidiosis
HIV Infections
Drug: Letrazuril
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Blinded, Placebo-Controlled, Single-Dose Pharmacokinetics and Dose Escalation, Efficacy, and Safety Study of Letrazuril for AIDS-Related Cryptosporidial Diarrhea

Resource links provided by NLM:


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

Estimated Enrollment: 32
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00001018

Locations
United States, California
USC School of Medicine
Los Angeles, California, United States, 90033
United States, New York
Cornell Univ Med Ctr
New York, New York, United States, 10021
Dr Douglas Dieterich
New York, New York, United States, 10016
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Sponsors and Collaborators
Janssen Pharmaceuticals
Investigators
Study Chair: Moskovitz BL
  More Information

Publications:
Guillem S, Gomez M, Romeu J, Raventos A, Fernandez A, Condom MJ, Clotet B. Letrazuril for the treatment of severe cryptosporidial diarrhoea in AIDS. Int Conf AIDS. 1992 Jul 19-24;8(2):B129 (abstract no PoB 3257)
Rubbert A, Schwab J, Kalden JR, Nusslein H. Myositis, fever, rash and thrombopenia after letrazuril treatment of intestinal cryptosporidiosis: a case report. Int Conf AIDS. 1993 Jun 6-11;9(1):373 (abstract no PO-B10-1430)

ClinicalTrials.gov Identifier: NCT00001018     History of Changes
Other Study ID Numbers: ACTG 198, Protocol JRD 65731/1001
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Cryptosporidiosis
Diarrhea
Acquired Immunodeficiency Syndrome
Antiprotozoal Agents
Triazines

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Cryptosporidiosis
Diarrhea
HIV Infections
Coccidiosis
Digestive System Diseases
Gastrointestinal Diseases
Immune System Diseases
Immunologic Deficiency Syndromes
Intestinal Diseases
Intestinal Diseases, Parasitic
Lentivirus Infections
Parasitic Diseases
Parasitic Diseases, Animal
Protozoan Infections
Protozoan Infections, Animal
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Signs and Symptoms
Signs and Symptoms, Digestive
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014