Ignite Creation Date:
2025-12-25 @ 12:12 AM
Ignite Modification Date:
2025-12-25 @ 10:14 PM
Study NCT ID:
NCT00017758
Status:
COMPLETED
Last Update Posted:
2006-03-14
First Post:
2001-06-11
Is NOT Gene Therapy:
False
Has Adverse Events:
False
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:
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 and/or 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 and/or 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 and/or 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 ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| AACTG A5108 | None | None | View |