Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00072644
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2003-11-06
Brief Title:
Pharmacokinetic Interactions With Prednisolone in Healthy Volunteers and HIV-infected Patients Receiving Single-Dose Prednisone
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Pharmacokinetic Interactions With Prednisolone in Healthy Volunteers and HIV-infected Patients Receiving Single-Dose Prednisone
Status:
COMPLETED
Status Verified Date:
2008-06-17
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:
This study will evaluate the impact of the HIV protease inhibitor ritonavir on the pharmacokinetics-that is the interaction of the medication and the body-of prednisolone after prednisone is given to healthy volunteers Prednisone an agent known as a corticosteroid or steroid hormone is converted by the body into prednisolone Ritonavir is an HIV medication that fights the virus by blocking its ability to reproduce Sometimes it increases the blood levels of other drugs given at the same time and it is possible that ritonavir increases the blood levels of prednisolone and those of other medications Results from the study will provide information on whether prednisone and ritonavir interact in a potentially harmful way The MDR1 genotype that is part of a persons genetic constitution may influence how prednisolone behaves
Patients 18 to 50 years of age who are in good health who not have HIV and who do not smoke may be eligible for this study There will be 10 participants and another 5 later who will be control subjects Those in the control group will take only prednisone not ritonavir
Participants will undergo the following tests and procedures
Medical history and physical examination
Collection of blood and urine to assess general health
Collection of blood to examine markers on white blood cells and to determine the kind of MDR1 gene was inherited
HIV test
The screening visit will take about 3 to 4 hours and the study will take about 28 to 49 days For 3 study days participants will remain in the clinic for 12 hours On Study Day 1 patients will be asked to not eat or drink anything besides water before coming to the clinic Blood samples will be collected to measure prednisolone concentration as well as osteocalcin a blood protein involved in bone formation Blood tests will also allow a look at the surfaces of some white blood cells Patients will receive a breakfast along with 20 mg of prednisone Urine samples will be collected also Then patients will be dismissed and asked to collect urine samples and return them on the following morning Study Day 2 At that time there will additional blood collection Patients will begin taking ritonavir between 7 and 28 days after the first dose of prednisone at a dose of 200 mg two 100 mg capsules twice daily with food to continue for 15 days On the 4th and 14th days of their taking ritonavir patients will be asked to visit the clinic in the morning for a blood to measure ritonavir in the blood and to take a single 20-mg dose of prednisone along with the ritonavir Both medications will be taken with breakfast Blood and urine levels of prednisolone will also be measured On the 15th day of ritonavir dosing there will be another blood collection for routine lab tests as well as studies on blood cells and osteocalcin
Patients 18 to 50 years of age who are in good health who not have HIV and who do not smoke may be eligible for this study There will be 10 participants and another 5 later who will be control subjects Those in the control group will take only prednisone not ritonavir
Participants will undergo the following tests and procedures
Medical history and physical examination
Collection of blood and urine to assess general health
Collection of blood to examine markers on white blood cells and to determine the kind of MDR1 gene was inherited
HIV test
The screening visit will take about 3 to 4 hours and the study will take about 28 to 49 days For 3 study days participants will remain in the clinic for 12 hours On Study Day 1 patients will be asked to not eat or drink anything besides water before coming to the clinic Blood samples will be collected to measure prednisolone concentration as well as osteocalcin a blood protein involved in bone formation Blood tests will also allow a look at the surfaces of some white blood cells Patients will receive a breakfast along with 20 mg of prednisone Urine samples will be collected also Then patients will be dismissed and asked to collect urine samples and return them on the following morning Study Day 2 At that time there will additional blood collection Patients will begin taking ritonavir between 7 and 28 days after the first dose of prednisone at a dose of 200 mg two 100 mg capsules twice daily with food to continue for 15 days On the 4th and 14th days of their taking ritonavir patients will be asked to visit the clinic in the morning for a blood to measure ritonavir in the blood and to take a single 20-mg dose of prednisone along with the ritonavir Both medications will be taken with breakfast Blood and urine levels of prednisolone will also be measured On the 15th day of ritonavir dosing there will be another blood collection for routine lab tests as well as studies on blood cells and osteocalcin
Detailed Description:
Corticosteroid administration has been associated with a variety of toxicities including osteonecrosis and Cushings Syndrome in patients with HIV infection The prevalence of these toxicities has led to speculation that protease inhibitors impair the cytochrome P450 CYP 3A4-mediated metabolism of corticosteroids leading to an increase in their systemic exposure and toxicity Conversely reduced corticosteroid exposure may be expected when these drugs are coadministrated with CYP3A4 inducers such as the non-nucleoside reverse transcriptase inhibitor NNRTI efavirenz Despite the hypothesized interaction between antiretroviral medications and corticosteroids drug interactions between agents from these classes have not been formally investigated The objectives of this study are 1 to determine the impact of the HIV protease inhibitor ritonavir on the pharmacokinetics of prednisolone after administration of oral prednisone to healthy volunteers and 2 to determine the respective influences of chronic dosing with lopinavir-ritonavir LPVr and efavirenz EFV on prednisolone pharmacokinetics in HIV individuals taking a single dose of prednisone For the HIV-negative healthy volunteer portion of the study 10 HIV-negative study subjects will receive a single 20 mg dose of prednisone before and after 3 and 14 days of ritonavir exposure at 200 mg twice daily Blood and urine will be collected over 24 hrs after prednisone administration to determine prednisolone pharmacokinetics and renal elimination Blood will also be collected for determination of MDR1 genotype which may influence prednisolone disposition For the portion of the study conducted in HIV-infected volunteers 3 groups of 10 subjects will be recruited to receive a single 20 mg dose of prednisone followed by serial blood sampling for prednisolone concentrations The 3 groups will consist of 1 individuals receiving and HIV treatment regimen for at least 30 days that includes LPVr 2 individuals receiving an HIV treatment regimen for at least 30 days that includes EFV and 3 individual receiving no antiretroviral treatment or treatment devoid of HIV protease inhibitors or NNRTIs Prednisolone concentrations will be determined by validated high performance chromatographic methods Non-compartmental methods will be used to characterize prednisolone pharmacokinetics in all study groups Pharmacokinetic parameter values will be compared using ANOVA with post-hoc testing Geometric mean data with 90 confidence intervals will be reported This study will characterize for the first time the influence of antiretroviral medications on the pharmacokinetics of a corticosteroid medication prednisolone
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-CC-0040 | None | None | None |