Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000654
Status:
COMPLETED
Last Update Posted:
2012-12-18
First Post:
1999-11-02
Brief Title:
The Tolerance of HIV-Infected Patients With Herpes Group Virus Infections to Oral Doses of FIAU
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
The Tolerance of HIV-Infected Patients With Herpes Group Virus Infections to Oral Doses of FIAU
Status:
COMPLETED
Status Verified Date:
2012-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
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
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 Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R90-001-01 02 03 04 | None | None | None |