Herpes SimplexPhase 2NCT00000654
The Tolerance of HIV-Infected Patients With Herpes Group Virus Infections to Oral Doses of FIAU
A Phase 2 study testing Fialuridine in people with Herpes Simplex and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial summary
To determine the tolerance of HIV-infected patients to TID oral doses of FIAU syrup at 4 different dose levels. To determine the peak and trough blood levels of FIAU and its metabolites during two weeks of oral dosing with FIAU. Read more about this study
- Who is it for?
- Ages 13 to 65 years
- Conditions the study is for
- Herpes Simplex, HIV Infections, Hepatitis B
- What is being tested?
- Fialuridine
- How many people
- 78 participants
- Where
- 4 sitesUnited States
- Study dates
- Start not givento Feb 1993
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Pentamidine aerosol for prophylaxis of recurrent Pneumocystis carinii pneumonia (PCP) in patients currently receiving such treatment.
- Zidovudine (AZT).
- Prior Medication:
- Allowed:
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- Zidovudine (AZT) but only if patient has been taking the drug for > 6 weeks at a dose = or < 600 mg/day, and had < 10 percent decrease in hematocrit, neutrophils, and platelets in the last 30 days.
- Patients must:
- Have a diagnosis of HIV infection by ELISA or Western blot. Be able to participate as an outpatient.
- Be ambulatory.
- Have Grade 0 or 1 AIDS Clinical Trial Group toxicity grades for specified laboratory tests.
- Be competent to sign informed consent.
- Be able to cooperate with the treatment plan and evaluation schedule.
- NOTE:
- The screening tests must be initiated and completed within 4 weeks prior to the first dose of FIAU, except for diagnostic herpes simplex virus (HSV), varicella zoster (VZV), or cytomegalovirus (CMV) cultures which may have been done previously.
- Concomitant diseases allowed:
- Stable mucocutaneous disease.
- Superficial or uncomplicated infections such as thrush.
Who cannot join
- Co-existing Condition:
- Patients with the following are excluded:
- HIV wasting syndrome (involuntary weight loss > 10 percent of baseline body weight and/or chronic diarrhea or weakness and documented fever for at least 30 days).
- Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis.
- Any unstable medical condition including serious infections or cardiovascular, oncologic, renal, or hepatic condition.
- Primary or initial infection with herpes simplex (HSV), varicella zoster (VZV), or hepatitis B (HBV).
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- Cytomegalovirus (CMV) end organ disease.
- Kaposi's sarcoma requiring chemotherapy.
- Systemic fungal infection requiring amphotericin therapy.
- Diagnosis of idiopathic thrombocytopenic purpura (persistent platelet counts < 100000 platelets/mm3 for = or > 3 months).
- Patients with the following are excluded:
- HIV wasting syndrome.
- Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis.
- Any unstable medical condition including serious cardiovascular, infections, oncologic, renal, or hepatic condition.
- Primary or initial infection with herpes simplex (HSV), varicella zoster (VZV), or hepatitis B (HBV).
- Cytomegalovirus (CMV) end organ disease.
- Prior Medication:
- Excluded within 4 weeks of study entry:
- Ganciclovir (DHPG).
- Foscarnet.
- Interferon.
- Other drug with putative antiviral activity (except zidovudine (AZT)).
- Any immunostimulating drug not specifically allowed.
- Excluded within 1 week of study entry:
- Acyclovir.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Natl Institute of Health
Bethesda, Maryland, 20892
Univ of Alabama at Birmingham
Birmingham, Alabama, 35294
Univ of California / San Diego Treatment Ctr
San Diego, California, 921036325
Univ of Washington / Madison Clinic
Seattle, Washington, 98122
About this study
To determine the tolerance of HIV-infected patients to TID oral doses of FIAU syrup at 4 different dose levels. To determine the peak and trough blood levels of FIAU and its metabolites during two weeks of oral dosing with FIAU.
The pyrimidine nucleoside analog FIAC and its primary deaminated uracil metabolite FIAU are highly and specifically active compounds in vitro against several herpes group viruses, particularly herpes simplex virus (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV), as well as hepatitis B virus (HBV). Since FIAU is the primary metabolite of FIAC and the administration of FIAU simplifies the metabolism of FIAC, it is anticipated from clinical studies of FIAC that FIAU will be tolerated at least as well as FIAC. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU. Daily oral doses are expected to provide concentrations of FIAU exceeding the in vitro minimum inhibitory concentration for nearly all the herpes group viruses.
Read the detailed description
The pyrimidine nucleoside analog FIAC and its primary deaminated uracil metabolite FIAU are highly and specifically active compounds in vitro against several herpes group viruses, particularly herpes simplex virus (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV), as well as hepatitis B virus (HBV). Since FIAU is the primary metabolite of FIAC and the administration of FIAU simplifies the metabolism of FIAC, it is anticipated from clinical studies of FIAC that FIAU will be tolerated at least as well as FIAC. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU. Daily oral doses are expected to provide concentrations of FIAU exceeding the in vitro minimum inhibitory concentration for nearly all the herpes group viruses.
HIV-infected patients with Karnofsky scores at least 80 (with or without documented recurrent herpes group infections) are successively entered into consecutively studied, escalating dose cohorts. There are a total of 4 dose cohorts of FIAU and each patient takes the required amount of FIAU syrup every 8 hours, 1 hour prior to or 3 hours after meals, for a total of 14 days. Entry of new patients at the next higher dose is based on results of tolerance and safety data for prior cohort when all 10 have received 14 days of therapy and at least 7 have met all of the tolerance criteria. Although not formally randomized due to the sequential nature of the study and serious medical condition of the patients, every attempt to avoid bias in assigning a patient to a dose is made. Patients are entered starting with the first dose cohort. Upon meeting the enrollment and tolerance criteria for dose escalation, up to 5 patients with a history of chronic HBV infection and surface antigen positive at their screening visit are added to the end of each dose cohort. Plasma samples are taken to determine peak and trough levels of FIAU at Days 1, 3, 7, and 14 or at last visit. Patients with ongoing active infections are followed by culture (HSV, VZV and CMV) or test (HBV) at Days 1, 3, 7, and 14. Antiemetic therapy with Reglan, Compazine, and Trilafon is given concomitantly at the discretion of the investigator and tolerance determined with antiemetic therapy ongoing. Patients are advised to avoid heavy exercise within 24 hours of any laboratory tests.
- Conditions
- Herpes Simplex, HIV Infections, Hepatitis B
- Being tested
- Fialuridine
- Keywords
- AIDS-Related Opportunistic Infections, Pyrimidine Nucleosides, Herpesviridae Infections, Drug Evaluation, Antiviral Agents, Hepatitis B
- Medical subject headings
- Herpes Simplex, HIV Infections, Hepatitis B, AIDS-Related Opportunistic Infections, Herpesviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FialuridineDrug
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)
- Study completionFeb 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Herpes SimplexStudies 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 2
- Primary purpose
- Treatment
- Enrolment
- 78 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Oclassen Pharmaceuticals
- Investigators
- D Richman, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000654
- Sponsor's protocol ID
- ACTG 122 FIAU
- Other IDs
- R90-001-01, 02, 03, 04
- Status last verified
- Dec 2012
- First submitted
- 2 Nov 1999
- Last updated
- 18 Dec 2012
- Results posted
- No
Publications
Tartaglione T, Hooton TM, Jones T, Smiles K, Corey L. Actg 122: phase II tolerance study of oral FIAU in HIV-infected persons. Int Conf AIDS. 1991 Jun 16-21;7(2):254 (abstract no WB2290)
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Tolerance of HIV-Infected Patients With Herpes Group Virus Infections to Oral Doses of FIAU
- ClinicalTrials.gov ID
- NCT00000654
- Acronym / sponsor ID
- ACTG 122 FIAU
- Conditions
- Herpes Simplex, HIV Infections, Hepatitis B
- Keywords
- AIDS-Related Opportunistic Infections, Pyrimidine Nucleosides, Herpesviridae Infections, Drug Evaluation, Antiviral Agents, Hepatitis B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Oclassen Pharmaceuticals
- Study completion
- Feb 1993 (actual)
- 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 tolerance of HIV-infected patients to TID oral doses of FIAU syrup at 4 different dose levels. To determine the peak and trough blood levels of FIAU and its metabolites during two weeks of oral dosing with FIAU.
The pyrimidine nucleoside analog FIAC and its primary deaminated uracil metabolite FIAU are highly and specifically active compounds in vitro against several herpes group viruses, particularly herpes simplex virus (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV), as well as hepatitis B virus (HBV). Since FIAU is the primary metabolite of FIAC and the administration of FIAU simplifies the metabolism of FIAC, it is anticipated from clinical studies of FIAC that FIAU will be tolerated at least as well as FIAC. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU. Daily oral doses are expected to provide concentrations of FIAU exceeding the in vitro minimum inhibitory concentration for nearly all the herpes group viruses.
Detailed description
The pyrimidine nucleoside analog FIAC and its primary deaminated uracil metabolite FIAU are highly and specifically active compounds in vitro against several herpes group viruses, particularly herpes simplex virus (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV), as well as hepatitis B virus (HBV). Since FIAU is the primary metabolite of FIAC and the administration of FIAU simplifies the metabolism of FIAC, it is anticipated from clinical studies of FIAC that FIAU will be tolerated at least as well as FIAC. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU. Daily oral doses are expected to provide concentrations of FIAU exceeding the in vitro minimum inhibitory concentration for nearly all the herpes group viruses.
HIV-infected patients with Karnofsky scores at least 80 (with or without documented recurrent herpes group infections) are successively entered into consecutively studied, escalating dose cohorts. There are a total of 4 dose cohorts of FIAU and each patient takes the required amount of FIAU syrup every 8 hours, 1 hour prior to or 3 hours after meals, for a total of 14 days. Entry of new patients at the next higher dose is based on results of tolerance and safety data for prior cohort when all 10 have received 14 days of therapy and at least 7 have met all of the tolerance criteria. Although not formally randomized due to the sequential nature of the study and serious medical condition of the patients, every attempt to avoid bias in assigning a patient to a dose is made. Patients are entered starting with the first dose cohort. Upon meeting the enrollment and tolerance criteria for dose escalation, up to 5 patients with a history of chronic HBV infection and surface antigen positive at their screening visit are added to the end of each dose cohort. Plasma samples are taken to determine peak and trough levels of FIAU at Days 1, 3, 7, and 14 or at last visit. Patients with ongoing active infections are followed by culture (HSV, VZV and CMV) or test (HBV) at Days 1, 3, 7, and 14. Antiemetic therapy with Reglan, Compazine, and Trilafon is given concomitantly at the discretion of the investigator and tolerance determined with antiemetic therapy ongoing. Patients are advised to avoid heavy exercise within 24 hours of any laboratory tests.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Pentamidine aerosol for prophylaxis of recurrent Pneumocystis carinii pneumonia (PCP) in patients currently receiving such treatment.
- Zidovudine (AZT).
- Zidovudine (AZT) but only if patient has been taking the drug for > 6 weeks at a dose = or < 600 mg/day, and had < 10 percent decrease in hematocrit, neutrophils, and platelets in the last 30 days.
- Have a diagnosis of HIV infection by ELISA or Western blot. Be able to participate as an outpatient.
- Be ambulatory.
Key exclusion criteria (25 listed)
- HIV wasting syndrome (involuntary weight loss > 10 percent of baseline body weight and/or chronic diarrhea or weakness and documented fever for at least 30 days).
- Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis.
- Any unstable medical condition including serious infections or cardiovascular, oncologic, renal, or hepatic condition.
- Primary or initial infection with herpes simplex (HSV), varicella zoster (VZV), or hepatitis B (HBV).
- Cytomegalovirus (CMV) end organ disease.
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 |
|---|---|---|
| Fialuridine | 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 18 Dec 2012.
- BackgroundTartaglione T, Hooton TM, Jones T, Smiles K, Corey L. Actg 122: phase II tolerance study of oral FIAU in HIV-infected persons. Int Conf AIDS. 1991 Jun 16-21;7(2):254 (abstract no WB2290)
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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.
D Richman 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 2 study testing Fialuridine in people with Herpes Simplex 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 18 inclusion and 25 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 18 Dec 2012. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 NCT00000654, which also lists 1 linked publication.
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 18 Dec 2012.