HCV Treatment: 4-week Lead-in With Nitazoxanide Before Peginterferon Plus Nitazoxanide

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HCV Treatment: 4-week Lead-in With Nitazoxanide Before Peginterferon Plus Nitazoxanide

SOURCE: Journal of Clinical Gastroenterology

Treatment of Chronic Hepatitis C Using a 4-week Lead-in With Nitazoxanide Before Peginterferon Plus NitazoxanideGOALS: The primary aim of this study was to further evaluate the efficacy of peginterferon plus nitazoxanide without ribavirin using a 4-week lead-in.

BACKGROUND: The initial treatment of chronic hepatitis C with nitazoxanide used 12 weeks of nitazoxanide monotherapy before combination therapy with peginterferon with or without ribavirin.

STUDY: This open-label pilot study enrolled 44 treatment-naive patients with chronic hepatitis C (40 with genotype 4; 3 with genotype 1; and 1 with genotype 2).

The patients received oral nitazoxanide 500 mg twice daily for 4 weeks followed by nitazoxanide plus peginterferon alfa-2a 180 mug weekly for 36 weeks and were then followed for 24 weeks. The results of this study were compared with those from an overlapping historical trial using 12 weeks of nitazoxanide lead-in.

RESULTS: A sustained virologic response (SVR) was achieved in 80% of patients, which was similar to the SVR rates in the historical trial, that is, 79% and 61% in patients treated with and without ribavirin, respectively. A rapid virologic response occurred in 59% of patients, which was also similar to the rapid virologic response rates in the historical trial (64% and 54% in patients treated with and without ribavirin, respectively). All 4 patients with genotypes 1 and 2 had an

SVR. CONCLUSIONS: The nitazoxanide lead-in phase before combination therapy with peginterferon can likely be reduced from 12 weeks to 4 weeks without compromising virologic response rates. In addition, treatment of chronic hepatitis C with peginterferon plus nitazoxanide without ribavirin is promising and requires further study.

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History

Nitazoxanide was originally discovered in the 1980s by François Rossignol at the Pasteur Institute. Initial studies demonstrated activity versus tapeworms. In vitro studies demonstrated much broader activity. Dr. Rossignol co-founded Romark Laboratories, with the goal of bringing nitazoxanide to market as an anti-parasitic drug. Initial studies in the USA were conducted in collaboration with Unimed Pharmaceuticals, Inc. (Marietta, GA) and focused on development of the drug for treatment of cryptosporidiosis in AIDS. Controlled trials began shortly after the advent of effective anti-retroviral therapies. The trials were abandoned due to poor enrollment and the FDA rejected an application based on uncontrolled studies.

Rather than abandon their efforts, Romark launched an impressive series of controlled trials. No other agent has proven efficacy in the treatment of cryptosporidiosis. However, a placebo-controlled study of nitazoxanide in cryptosporidiosis demonstrated significant clinical improvement in adults and children with mild illness. Among malnourished children in Zambia with chronic cryptosporidiosis, a three-day course of therapy not only led to clinical and parasitologic improvement, but also improved survival. In Zambia and in a study conducted in Mexico, nitazoxanide was not successful in the treatment of cryptosporidiosis in advanced infection with human immunodeficiency virus at the doses used. However, it was effective in patients with higher CD4 counts. Also, higher doses seem to have some effect in uncontrolled and unpublished studies. In treatment of giardiasis, nitazoxanide was superior to placebo and comparable to metronidazole. Nitazoxanide was successful in the treatment of metronidazole-resistant giardiasis. Studies have suggested efficacy in the treatment of cyclosporiasis, isosporiasis, and amebiasis

UsesNitazoxanide is a first-line choice for the treatment of illness caused by Cryptosporidium parvum or Giardia lamblia infection in immunocompetent adults and children, and is an option to be considered in the treatment of illness caused by other protozoa and/or helminths.[3]It is used for the treatment of infectious diarrhea caused by Cryptosporidium parvum[4] and Giardia lamblia[5] in

patients 1 year of age and older.Nitazoxanide is currently in Phase II clinical trials for the treatment of hepatitis C, in combination with peginterferon alfa-2a and ribavirin.[6][7]

A randomised double-blind placebo-controlled study published in 2006, with a group of 38 young children (Lancet, vol 368, page 124-129)[8] concluded that a 3-day course of nitazoxanide significantly reduced the duration of rotavirus disease in hospitalized pediatric patients. Dose given was "7.5 mg/kg twice daily" and the time of resolution was "31 hours for those given nitazoxanide compared with 75 hours for those in the placebo group." It is to be noted that rotavirus is the most common infectious agent associated with diarrhea in the pediatric age group worldwide.[9]

Teran et al. conducted a study at the Pediatric Center Albina Patinö, a reference hospital in the city of Cochabamba, Bolivia, from August 2007 to February 2008. The study compared nitazoxanide and probiotics in the treatment of acute rotavirus diarrhea. They found Small differences in favor of nitazoxanide in comparison with probiotics and concluded that nitazoxanide is an important treatment option for rotavirus diarrhea.[10]

Romark Laboratories has announced encouraging results from international Phase I and II clinical trials evaluating a controlled release version of nitazoxanide in the treatment of chronic hepatitis C virus infection. The company used 675 mg and 1,350 mg twice daily doses of controlled release nitazoxanide Controlled release nitazoxanide showed favorable safety and tolerability throughout the course of the study, with mild to moderate adverse events. Primarily GI-related adverse events were reported.[11]Lateef et al. conducted a study in India that evaluated the effectiveness of nitazoxanide in the treatment of beef tapeworm (Taenia saginata) infection.

They concluded that nitazoxanide is a safe, effective, inexpensive, and well-tolerated drug for the treatment of niclosamide- and praziquantel-resistant beef tapeworm (Taenia saginata) infection.[12]A retrospective review of charts of patients treated with nitazoxanide for trichomoniasis by Dan and Jack D. Sobel demonstrated negative result. They reported three case studies; two of which with metronidazole-resistant infections. In Case 3, they reported the patient to be cured with high divided dose tinidazole therapy.

They used a high dosage of the drug (total dose, 14–56 g) than the recommended standard dosage (total dose, 3 g) and observed a significant adverse reaction (poorly tolerated nausea) only with the very high dose (total dose, 56 g). Though the output they got is in favor of safety of the drug but their experience was really disappointing in the treatment of trichomoniasis with nitazoxanide.[13]

] Adverse effectsSide effects are mostly gastrointestinal, and include abdominal pain, vomiting, headache, nausea and diarrhea.In the clinical trials no serious adverse events were reported. No serious adverse events were reported in the prescribing information of the parent company.[14]

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