Official Title: “Phase I/II Open Label Evaluation of Nitazoxanide for the Treatment of Cryptosporidiosis in AIDS Patients”

To determine the pharmacokinetics profile of single doses of nitazoxanide (NTZ) in patients with AIDS-related cryptosporidial diarrhea. To determine steady state concentrations of NTZ following repeated dosing. To assess the safety and efficacy of 4 dose levels of NTZ in these patients.

Cryptosporidial enterocolitis in AIDS patients is frequently chronic and severe, contributing substantially to morbidity, mortality, and health care costs in this population. NTZ exhibits antimicrobial activity that may extend to Cryptosporidial infection.

Study Type: Interventional

Study Design: Treatment, Dose Comparison, Pharmacokinetics Study

Cryptosporidial enterocolitis in AIDS patients is frequently chronic and severe, contributing substantially to morbidity, mortality, and health care costs in this population. NTZ exhibits antimicrobial activity that may extend to Cryptosporidial infection.

Patients are enrolled in groups of 7. Group A receives the lowest dose of NTZ. Groups B - D receive sequentially higher doses. Patients in Groups B - D do not begin therapy until all patients have been enrolled at the preceding dose. For determination of single-dose pharmacokinetics, patients receive a single dose of NTZ on Day 1 and blood samples are obtained over the next 24 hours. Immediately following the 24-hour blood sample collection, patients begin the treatment phase during which they take NTZ for an additional 13 days.

Blood samples are obtained again on Day 14 to determine full plasma concentration-time profiles over the dosing interval. At the end of treatment, responders discontinue treatment and nonresponders continue NTZ treatment for an additional 14 days on the same dose. Patients who still fail to respond are provided with an additional month of NTZ. Patients have scheduled visits for clinical and parasitologic efficacy assessments and safety laboratory tests.

Intervention(s) in this Clinical Trial

• Drug: Nitazoxanide

Inclusion Criteria

Patients must have:

• AIDS diagnosis according to CDC criteria.
• CD4 count less than or equal to 200 cells/mm3 or CD4 count greater than or equal to 200 cells/mm3 and documented cryptosporidiosis for a minimum of 4 weeks.
• Cryptosporidial diarrhea as defined by:
• (1) presence of Cryptosporidium oocytes in a stool specimen within 14 days of enrollment; and (2) chronic diarrhea (i.e., an average of at least 4 bowel movements per day for a minimum of 2 weeks).
• Life expectancy of at least 1 month.
• Ability to tolerate food by mouth.

Prior Medication:

Required:

• Any anti-diarrheal or anti-emetic medication for which the dosage regimen has been stable for at least 1 week prior to enrollment.
• Any antiretroviral medications (e.g., zidovudine, ddI, ddC) for which the dosage regimen has been stable for at least 3 weeks prior to enrollment.

Allowed:

• Medication for prophylaxis or maintenance therapy of opportunistic infection, stable for at least 2 weeks prior to enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Grade 4 (hematologic) or Grade 3 (for all others) toxicity. (Patients with Grade 3 toxicity for hepatic parameters may be enrolled if, in the investigator's judgment, the abnormalities are due to biliary cryptosporidiosis.)

Patients with the following prior conditions are excluded:

• Presence of Salmonella, Shigella, Campylobacter, Yersinia, Giardia lamblia, Entamoeba histolytica, Microsporidia, Isospora, Cyclospora, or Clostridium difficile toxin in stool (based on assessment within 14 days prior to enrollment by stool ova and parasite examination, culture, and C.
• difficile assay).
• History of intestinal Mycobacterium avium intracellular infection or intestinal
• Kaposi's sarcoma.
• History of Cytomegalovirus colitis, unless 28 days of therapy with ganciclovir or foscarnet completed subsequent to diagnosis.

Prior Medication:

Excluded:

• Investigational drug therapy within 14 days of enrollment, unless available under an FDA-authorized expanded access program.
• Any drug or therapy with possible anticryptosporidial activity (e.g., paromomycin, spiramycin, azithromycin, clarithromycin, hyperimmune bovine colostrum) within 14 days of enrollment.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Unimed Pharmaceuticals

Overall Clinical Trial Officials and Contacts

Rosemary Soave Principal Investigator   

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002444

Study ID Number: 253A

ClinicalTrials.gov Identifier: NCT00002444

Health Authority: United States: Food and Drug Administration