HIV InfectionsPhase 1NCT00017758
The Effect of Efavirenz and Nelfinavir on the Blood Levels of Certain Lipid-Lowering Drugs
A Phase 1 study testing Pravastatin sodium, Simvastatin and Atorvastatin calcium in people with HIV Infections and HIV Seronegativity, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, HIV Seronegativity, Lipodystrophy
- What is being tested?
- Pravastatin sodium, Simvastatin and Atorvastatin calcium
- How many people
- 56 participants
- Where
- 10 sitesUnited States
- Study dates
- Start not givento not given
- Phase
- Phase 1
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Volunteers may be eligible for this study if they:
- Are HIV-negative.
- Are 18 to 60 years old.
- Weigh at least 50 kg (110 lbs) and are within 30 percent of their ideal body weight.
- Cannot have children (have reached menopause [change of life] for at least 24 straight months or have had a hysterectomy), if female and enrolling to Group A, B, or C.
- Have a negative pregnancy test within 14 days before study entry and within 24 hours before starting the study drugs, if female, able to have children, and enrolling to Group D.
- Agree to avoid trying to become pregnant or causing someone to become pregnant. Agree not to donate sperm or participate in other fertilization procedures. If participating in sexual activity that could lead to pregnancy, the study volunteer and/or partner must use 2 reliable methods of birth control at the same time, while taking study drugs, and for 6 weeks after stopping the drugs. Male volunteers are allowed to be sexually active without the use of birth control if they have had a successful vasectomy or are sterile.
Who cannot join
- Volunteers will not be eligible for this study if they:
- Have or have had heart, kidney, blood, nerve, digestive, mental, hormonal, or immune system diseases. These include high blood pressure, blocked arteries, arthritis, diabetes, stomach or intestinal problems, depression, and past use of antidepressant drugs.
- Are pregnant or breast-feeding.
- Have used experimental, prescription, or over-the-counter drugs within 14 days before study entry, except for aspirin (ASA), acetaminophen (Tylenol), diphenhydramine (Benadryl), daily multivitamins, mineral supplements, birth control pills or implants, and hormone replacement therapy for women who have reached menopause.
- Are allergic to study drugs or their ingredients.
- Abuse drugs or alcohol.
Show all 10Show fewer
- Have a medical condition that, in the opinion of the investigator, would interfere with their participation in the study.
- Have participated in any experimental drug study within 30 days before study entry.
- Are not able to keep their usual diet during the study or are unable to write down their food intake before the study visits.
- Have an abnormal urine test result, e.g., urinary tract infection, kidney disease, or kidney stones.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins Hosp
Baltimore, Maryland, 21287
Univ of Cincinnati
Cincinnati, Ohio, 452670405
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262
Univ of Minnesota
Minneapolis, Minnesota, 55455
Univ of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Univ of Rochester Medical Center
Rochester, New York, 14642
Univ of Washington
Seattle, Washington, 98104
Washington Univ / St Louis Connect Care
St Louis, Missouri, 63108
Washington Univ School of Medicine
St Louis, Missouri, 63108
Stanford Univ Med Ctr
Stanford, California, 943055107
About this study
Official title: The Effect of Efavirenz and Nelfinavir on the Pharmacokinetics of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors
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.
Read the 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.
- Conditions
- HIV Infections, HIV Seronegativity, Lipodystrophy
- Being tested
- Pravastatin sodium, Simvastatin, Atorvastatin calcium, Nelfinavir mesylate, Efavirenz
- Keywords
- Drug Interactions, Nelfinavir, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Pharmacokinetics, Pravastatin, efavirenz, Simvastatin, atorvastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Medical subject headings
- HIV Infections, Lipodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pravastatin sodiumDrug
SimvastatinDrug
Atorvastatin calciumDrug
Nelfinavir mesylateDrug
EfavirenzDrug
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)
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 HIV InfectionsStudies 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 1
- Primary purpose
- Treatment
- Enrolment
- 56 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- John Gerber, Study chairJudith Aberg, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00017758
- Sponsor's protocol ID
- ACTG A5108
- Other IDs
- AACTG A5108
- Status last verified
- Feb 2004
- First submitted
- 11 Jun 2001
- Last updated
- 14 Mar 2006
- Results posted
- No
Publications
Aberg JA, Rosenkranz SL, Fichtenbaum CJ, Alston BL, Brobst SW, Segal Y, Gerber JG; ACTG A5108 team. Pharmacokinetic interaction between nelfinavir and pravastatin in HIV-seronegative volunteers: ACTG Study A5108. AIDS. 2006 Mar 21;20(5):725-9. doi: 10.1097/01.aids.0000216373.53819.92.
PubMed 16514303
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Efavirenz and Nelfinavir on the Pharmacokinetics of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors
- ClinicalTrials.gov ID
- NCT00017758
- Acronym / sponsor ID
- ACTG A5108
- Conditions
- HIV Infections, HIV Seronegativity, Lipodystrophy
- Keywords
- Drug Interactions, Nelfinavir, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Pharmacokinetics, Pravastatin, efavirenz, Simvastatin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- 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.
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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Are HIV-negative.
- Are 18 to 60 years old.
- Weigh at least 50 kg (110 lbs) and are within 30 percent of their ideal body weight.
- Cannot have children (have reached menopause [change of life] for at least 24 straight months or have had a hysterectomy), if female and enrolling to Group A, B, or C.
- Have a negative pregnancy test within 14 days before study entry and within 24 hours before starting the study drugs, if female, able to have children, and enrolling to Group D.
Key exclusion criteria (10 listed)
- Have or have had heart, kidney, blood, nerve, digestive, mental, hormonal, or immune system diseases. These include high blood pressure, blocked arteries, arthritis, diabetes, stomach or intestinal problems, depression, and past use of antidepressant drugs.
- Are pregnant or breast-feeding.
- Have used experimental, prescription, or over-the-counter drugs within 14 days before study entry, except for aspirin (ASA), acetaminophen (Tylenol), diphenhydramine (Benadryl), daily multivitamins, mineral supplements, birth control pills or implants, and hormone replacement therapy for women who have reached menopause.
- Are allergic to study drugs or their ingredients.
- Abuse drugs or alcohol.
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 |
|---|---|---|
| Pravastatin sodium | Drug | – |
| Simvastatin | Drug | – |
| Atorvastatin calcium | Drug | – |
| Nelfinavir mesylate | Drug | – |
| Efavirenz | 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 14 Mar 2006.
- Results publication: PubMed 16514303Aberg JA, Rosenkranz SL, Fichtenbaum CJ, Alston BL, Brobst SW, Segal Y, Gerber JG; ACTG A5108 team. Pharmacokinetic interaction between nelfinavir and pravastatin in HIV-seronegative volunteers: ACTG Study A5108. AIDS. 2006 Mar 21;20(5):725-9. doi: 10.1097/01.aids.0000216373.53819.92.
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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.
John Gerber study chair
Judith Aberg study chair
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pravastatin sodium, Simvastatin and Atorvastatin calcium in people with HIV Infections and HIV Seronegativity, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 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 7 inclusion and 10 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 14 Mar 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 NCT00017758, 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 14 Mar 2006.