Blinded, Placebo-Controlled, Single-Dose Pharmacokinetics and Dose Escalation, Efficacy, and Safety Study of Letrazuril for AIDS-Related Cryptosporidial Diarrhea

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.

Start Date-

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

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100 Clinical Results associated with Letrazuril

100 Translational Medicine associated with Letrazuril

100 Patents (Medical) associated with Letrazuril

Literatures (Medical) associated with Letrazuril

01 Dec 2021·International Journal for Parasitology: Drugs and Drug ResistanceQ2 · MEDICINE

Treatment of human intestinal cryptosporidiosis: A review of published clinical trials

Q2 · MEDICINE

ReviewOA

Author: Diptyanusa, Ajib ; Sari, Ika Puspa

The global burden of diarrhea caused by Cryptosporidium parasite is underestimated. In immunocompromised hosts, chronic and severe presentation of intestinal cryptosporidiosis can result in long-term morbidity and high illness costs. The evidence of effective treatments for cryptosporidiosis has been lacking. We reviewed the published clinical trials to bring forward the feasible therapeutic options of human cryptosporidiosis in various populations and settings according to clinical improvement and parasite clearance rates. A total of 42 studies consisting of the use of nitazoxanide, paromomycin, macrolides, somatostatin analogues, letrazuril, albendazole, rifaximin, miltefosine, clofazimine, and colostrum were included in the review. The trials were mostly conducted in small number of individuals infected with human immunodeficiency virus (HIV), and there is inadequate data of controlled trials to suggest the use of these treatment modalities. Nitazoxanide was reported to be highly efficacious only in immunocompetent hosts and was found to be superior to paromomycin in the same group of patients. Macrolides showed no effective results in both clinical and parasitological improvement. Human bovine colostrum should possibly be administered as one of complementary therapeutic modalities along with other antimicrobials to reach optimal parasite eradication. Other trials of therapeutic modalities were terminated due to futility. Currently, available data is intended to aid the development of strategies for improving access to treatments in different clinical settings, as well as to help guide further studies on treatments of human intestinal cryptosporidiosis.

01 Feb 1997·International Journal of STD & AIDSQ4 · MEDICINE

Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis

Q4 · MEDICINE

Article

Author: Gazzard, B G ; Blanshard, C ; Shanson, D C

Summary: Pilot studies of the safety and efficacy of 3 drugs thought to have anticryptosporidial activity were carried out to determine whether any of them are suitable for large-scale clinical trials. Open studies of the use of azithromycin, letrazuril and paromomycin in patients with acquired immunodeficiency syndrome (AIDS) and confirmed cryptosporidial diarrhoea for at least a month. Azithromycin 500 mg daily was ineffective. Letrazuril 150-200 mg daily was associated with an improvement in symptoms in 40% of patients treated and cessation of excretion of cryptosporidial oocysts in the stool in 70%; however biopsies remained positive. Paromomycin therapy was associated with a complete resolution of diarrhoea in 60% of patients treated and some improvement in symptoms in a further 5% but it did not eliminate the infection. None of the drugs had any major toxicities. Dose escalation studies of azithromycin should be performed. Letrazuril should be further investigated for efficacy in double-blind placebo-controlled trials. Paromomycin appears to result in prolonged symptomatic remission of cryptosporidial diarrhoea, but has no effect on cryptosporidial cholangitis.

01 Sep 1995·Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology

Treatment with Letrazuril of Refractory Cryptosporidial Diarrhea Complicating AIDS

Article

Author: Rachlis, A. ; Loeb, M. ; Walach, C. ; Salit, I. ; Fong, I. ; Walmsley, S. ; Phillips, J.

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.

100 Deals associated with Letrazuril

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Indication	Highest Phase	Country/Location	Organization	Date
Cryptosporidiosis	Phase 1	US	Janssen Pharmaceuticals, Inc.	31 Aug 2001
HIV Infections	Phase 1	US	Janssen Pharmaceuticals, Inc.	31 Aug 2001

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