Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00017758
Status:
COMPLETED
Last Update Posted:
2006-03-14
First Post:
2001-06-11
Brief Title:
The Effect of Efavirenz and Nelfinavir on the Blood Levels of Certain Lipid-Lowering Drugs
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
The Effect of Efavirenz and Nelfinavir on the Pharmacokinetics of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors
Status:
COMPLETED
Status Verified Date:
2004-02
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:
The purpose of this study is to find out whether certain anti-HIV drugs efavirenz EFV and nelfinavir NFV affect the amount of certain fat-lowering drugs atorvastatin pravastatin and simvastatin in the blood
Protease inhibitors PIs a type of anti-HIV drug are known to cause increased lipids fats in the blood of HIV-infected patients EFV also is known to increase blood fats HIV-infected patients who take PIs andor EFV may need to take fat-lowering drugs to correct this problem So it is important to look at possible drug interactions when these drugs are taken together This study will see if taking EFV or NFV a protease inhibitor affects the blood level of simvastatin atorvastatin or pravastatin all fat-lowering drugs To obtain results more quickly the study population will be healthy HIV-negative volunteers
Protease inhibitors PIs a type of anti-HIV drug are known to cause increased lipids fats in the blood of HIV-infected patients EFV also is known to increase blood fats HIV-infected patients who take PIs andor EFV may need to take fat-lowering drugs to correct this problem So it is important to look at possible drug interactions when these drugs are taken together This study will see if taking EFV or NFV a protease inhibitor affects the blood level of simvastatin atorvastatin or pravastatin all fat-lowering drugs To obtain results more quickly the study population will be healthy HIV-negative volunteers
Detailed Description:
Abnormalities in lipid metabolism are a recognized side effect of protease inhibitor PI therapy in HIV-infected patients EFV also is known to increase plasma cholesterol In an attempt to normalize serum lipids in HIV-infected patients on PIs andor EFV Hydroxymethylglutaryl Coenzyme A HMG-CoA reductase inhibitors also known as statins may be prescribed Therefore it is important to study how PIs and EFV affect the PK of concurrently-administered statins Many of the statins utilize the cytochrome P450 CYP 3A4 enzyme for metabolism In addition atorvastatin and simvastatin have active metabolites generated via CYP3A4 that contribute to the drugs lipid-lowering activity and probably to their toxicity Pravastatin is not metabolized by CYP3A4 but is inactivated by conjugation non-CYP3A4-induced hydroxylation and renal excretion NFV the most commonly used PI is an inhibitor of CYP3A4 and an inducer of other CYPs and conjugative pathways EFV is a mixed CYP3A4 inhibitor and inducer This study examines the effect of NFV on the PK of pravastatin and the effect of EFV on the PK of simvastatin atorvastatin and pravastatin As EFV with pravastatin is expected to be a common drug combination during the treatment of HIV infection it should be explored further even though drug interactions are not expected To expedite this study the study population is comprised of healthy control volunteers
Volunteers are assigned to 1 of 4 groups Volunteers in Groups A B and C take a statin simvastatin atorvastatin or pravastatin respectively on Days 0 to 3 After Day 3 the statin is stopped and EFV is begun Volunteers take EFV until Day 14 and the statin and EFV together from Days 15 to 18 Volunteers in Group D take pravastatin on Days 0 to 3 NFV on Days 4 to 12 and pravastatin and NFV together on Days 13 to 16 Fasting lipid profiles are performed on Days 0 4 15 and 19 for Groups A B and C and on Days 0 3 13 and 16 for Group D PK sampling is performed on Days 3 14 and 18 for Groups A B and C requiring an overnight stay and on Days 3 and 16 for Group D Volunteers receive monetary compensation for participation in this study
Volunteers are assigned to 1 of 4 groups Volunteers in Groups A B and C take a statin simvastatin atorvastatin or pravastatin respectively on Days 0 to 3 After Day 3 the statin is stopped and EFV is begun Volunteers take EFV until Day 14 and the statin and EFV together from Days 15 to 18 Volunteers in Group D take pravastatin on Days 0 to 3 NFV on Days 4 to 12 and pravastatin and NFV together on Days 13 to 16 Fasting lipid profiles are performed on Days 0 4 15 and 19 for Groups A B and C and on Days 0 3 13 and 16 for Group D PK sampling is performed on Days 3 14 and 18 for Groups A B and C requiring an overnight stay and on Days 3 and 16 for Group D Volunteers receive monetary compensation for participation in this study
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 |
|---|---|---|---|
| AACTG A5108 | None | None | None |