CryptosporidiosisPhase 1NCT00001018
A Study of Letrazuril in the Treatment of AIDS-Related Diarrhea
A Phase 1 study testing Letrazuril in people with Cryptosporidiosis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Cryptosporidiosis, HIV Infections
- What is being tested?
- Letrazuril
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- Start not givento not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
USC School of Medicine
Los Angeles, California, 90033
Dr Douglas Dieterich
New York, New York, 10016
Cornell Univ Med Ctr
New York, New York, 10021
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, 10025
About this study
Official title: 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.
Read the 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.
- Conditions
- Cryptosporidiosis, HIV Infections
- Being tested
- Letrazuril
- Keywords
- Cryptosporidiosis, Diarrhea, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, Triazines
- Medical subject headings
- Cryptosporidiosis, HIV Infections, Diarrhea, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrazurilDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for CryptosporidiosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 32 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Janssen Pharmaceuticals
- Investigators
- Moskovitz BL, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001018
- Sponsor's protocol ID
- ACTG 198
- Other IDs
- Protocol JRD 65731/1001
- Status last verified
- Oct 1992
- First submitted
- 2 Nov 1999
- Last updated
- 24 Jun 2005
- Results posted
- No
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)
Harris M, Deutsch G, MacLean JD, Tsoukas CM. A phase I study of letrazuril in AIDS-related cryptosporidiosis. AIDS. 1994 Aug;8(8):1109-13. doi: 10.1097/00002030-199408000-00011.
PubMed 7986407Rubbert 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)
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blinded, Placebo-Controlled, Single-Dose Pharmacokinetics and Dose Escalation, Efficacy, and Safety Study of Letrazuril for AIDS-Related Cryptosporidial Diarrhea
- ClinicalTrials.gov ID
- NCT00001018
- Acronym / sponsor ID
- ACTG 198
- Conditions
- Cryptosporidiosis, HIV Infections
- Keywords
- Cryptosporidiosis, Diarrhea, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, Triazines
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Janssen Pharmaceuticals
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 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).
Key exclusion criteria (14 listed)
- 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.
- Ganciclovir, cancer chemotherapy, or interferon-alpha or other immunomodulating agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Letrazuril | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2005.
- BackgroundGuillem 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)
- Background: PubMed 7986407Harris M, Deutsch G, MacLean JD, Tsoukas CM. A phase I study of letrazuril in AIDS-related cryptosporidiosis. AIDS. 1994 Aug;8(8):1109-13. doi: 10.1097/00002030-199408000-00011.
- BackgroundRubbert 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Moskovitz BL study chair
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Letrazuril in people with Cryptosporidiosis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001018, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2005.