HIV InfectionsPhase 1NCT00039975
Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers
A Phase 1 study testing Indinavir sulfate, Ritonavir and Amlodipine in people with HIV Infections and Cardiovascular Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in United States.
Trial summary
Diltiazem CD and amlodipine are drugs used to treat heart disease and high blood pressure. The purpose of this study is to find out if these drugs interact with the anti-HIV drugs indinavir and ritonavir. The study will also look at the safety of taking the study drugs together. 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, Cardiovascular Diseases, Hypertension
- What is being tested?
- Indinavir sulfate, Ritonavir and Amlodipine
- How many people
- 32 participants
- Where
- 9 sitesUnited States
- Study dates
- Start not givento Apr 2004
- 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
- Patients may be eligible for this study if they:
- Are HIV-negative.
- Are between the ages of 18 and 60.
- Agree not to become pregnant or to impregnate and to use an acceptable form of contraception while receiving study drugs and for 1 month after stopping study drugs. Patients who are not of reproductive potential are eligible without the contraception requirement.
- Are within 30 percent of ideal body weight.
- Weigh at least 110 lbs.
Who cannot join
- Patients may not be eligible for this study if they:
- Have a history of any illness that requires current medical therapy.
- Have a history of any kidney disorder.
- Have any medical condition that, in the opinion of the investigator, would interfere with the study.
- Are pregnant or breast-feeding.
- Use certain drugs within 14 days prior to study entry.
Show all 12Show fewer
- Are allergic or sensitive to study drugs.
- Use drugs or alcohol in a way which, in the opinion of the investigator, would interfere with the study.
- Have any abnormality on electrocardiogram within 21 days prior to study entry.
- Participate in any investigational drug studies within 21 days prior to study entry and during study.
- Are unable to participate in pharmacokinetic visits.
- Are unable to understand or follow the fluid intake requirement during the periods of IDV/RTV administration.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 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
Cornell Univ Med Ctr
New York, New York, 10021
Univ of Rochester Medical Center
Rochester, New York, 14642
Univ of California San Francisco
San Francisco, California, 94110
Washington Univ (St. Louis)
St Louis, Missouri, 63108
Stanford Univ Med Ctr
Stanford, California, 943055107
About this study
Official title: Evaluation of Potential Pharmacokinetic Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers
Diltiazem CD and amlodipine are drugs used to treat heart disease and high blood pressure. The purpose of this study is to find out if these drugs interact with the anti-HIV drugs indinavir and ritonavir. The study will also look at the safety of taking the study drugs together.
Heart disease and high blood pressure are major health concerns for people with HIV. Standard treatment for these illnesses often includes calcium channel blockers (CCBs). There is a potential for significant drug interactions between CCBs and HIV protease inhibitors (PIs) that may influence the dosing, monitoring, and choosing of CCBs and PIs when used in people infected with HIV. This study will examine the drug interactions between 2 commonly used CCBs and the PI combination indinavir and ritonavir (IDV/RTV). This information should help doctors choose the appropriate treatment for high blood pressure or heart disease in people taking PIs.
Read the detailed description
Ischemic cardiovascular disease and hypertension occur in persons with HIV infection, and the incidence and prevalence may increase over time as the infected population ages. Standard pharmacologic interventions for these illnesses often include calcium channel blockers (CCBs). Many of the calcium channel blockers are metabolized by cytochrome P450 3A4 (CYP 3A4), which is inhibited by some protease inhibitors (PIs). Thus, there is potential for clinically significant interactions between CCBs and PIs. The presence of significant drug-drug interactions may influence the dosing, monitoring, and choosing of CCBs and/or PIs when used in persons with HIV infection. Because of the potential concomitant use of CCBs with the PI combination IDV/RTV, this study will evaluate bi-directional drug-drug interactions between 2 commonly used CCBs and IDV/RTV. This information should assist clinicians in choosing the appropriate CCBs to treat hypertension or cardiovascular disease in persons taking PIs.
Patients are randomized to 1 of the following 2 arms:
Arm A: diltiazem CD interaction with IDV and RTV. Arm B: amlodipine interaction with IDV and RTV. From Days 1 to 7, patients take diltiazem CD (Arm A) or amlodipine (Arm B). Plasma is collected for PK over a 24-hour period beginning on Day 7. From Days 8 to 19, patients stop taking their assigned CCB and take IDV and RTV. Plasma is collected for PK over a 12-hour period on Day 19. From Days 20 to 26, patients continue to take IDV and RTV and add diltiazem CD (Arm A) or amlodipine (Arm B). Patients stop all 3 drugs after the last dose on Day 26. Plasma is collected for PK for a 24-hour period beginning on Day 26. Blood work, liver and kidney function tests, urinalysis, and an electrocardiogram (EKG) are performed at some visits.
- Conditions
- HIV Infections, Cardiovascular Diseases, Hypertension
- Being tested
- Indinavir sulfate, Ritonavir, Amlodipine, Diltiazem HCl
- Keywords
- Drug Interactions, HIV Protease Inhibitors, Ritonavir, Indinavir, Calcium Channel Blockers, Pharmacokinetics, Diltiazem, Amlodipine
- Medical subject headings
- HIV Infections, Cardiovascular Diseases, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indinavir sulfateDrug
RitonavirDrug
AmlodipineDrug
Diltiazem HClDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2002 (estimated)
- Study completionApr 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Masking
- None (open label)
- Enrolment
- 32 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marshall Glesby, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00039975
- Sponsor's protocol ID
- A5159
- Other IDs
- 10959, ACTG A5159, AACTG A5159
- Status last verified
- Oct 2021
- First submitted
- 18 Jun 2002
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
Yunis NA, Stone VE. Cardiac manifestations of HIV/AIDS: a review of disease spectrum and clinical management. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jun 1;18(2):145-54. doi: 10.1097/00042560-199806010-00006.
PubMed 9637579Henry K, Melroe H, Huebsch J, Hermundson J, Levine C, Swensen L, Daley J. Severe premature coronary artery disease with protease inhibitors. Lancet. 1998 May 2;351(9112):1328. doi: 10.1016/S0140-6736(05)79053-X. No abstract available.
PubMed 9643798Cattelan AM, Trevenzoli M, Sasset L, Rinaldi L, Balasso V, Cadrobbi P. Indinavir and systemic hypertension. AIDS. 2001 Apr 13;15(6):805-7. doi: 10.1097/00002030-200104130-00021. No abstract available.
PubMed 11371700Passalaris JD, Sepkowitz KA, Glesby MJ. Coronary artery disease and human immunodeficiency virus infection. Clin Infect Dis. 2000 Sep;31(3):787-97. doi: 10.1086/313995. Epub 2000 Oct 4.
PubMed 11017831Glesby MJ, Aberg JA, Kendall MA, Fichtenbaum CJ, Hafner R, Hall S, Grosskopf N, Zolopa AR, Gerber JG; Adult AIDS Clinical Trials Group A5159 Protocol Team. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clin Pharmacol Ther. 2005 Aug;78(2):143-53. doi: 10.1016/j.clpt.2005.04.005.
PubMed 16084849
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Potential Pharmacokinetic Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers
- ClinicalTrials.gov ID
- NCT00039975
- Acronym / sponsor ID
- A5159
- Conditions
- HIV Infections, Cardiovascular Diseases, Hypertension
- Keywords
- Drug Interactions, HIV Protease Inhibitors, Ritonavir, Indinavir, Calcium Channel Blockers, Pharmacokinetics, Diltiazem, Amlodipine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Apr 2004 (actual)
- First posted
- 20 Jun 2002 (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.
Diltiazem CD and amlodipine are drugs used to treat heart disease and high blood pressure. The purpose of this study is to find out if these drugs interact with the anti-HIV drugs indinavir and ritonavir. The study will also look at the safety of taking the study drugs together.
Heart disease and high blood pressure are major health concerns for people with HIV. Standard treatment for these illnesses often includes calcium channel blockers (CCBs). There is a potential for significant drug interactions between CCBs and HIV protease inhibitors (PIs) that may influence the dosing, monitoring, and choosing of CCBs and PIs when used in people infected with HIV. This study will examine the drug interactions between 2 commonly used CCBs and the PI combination indinavir and ritonavir (IDV/RTV). This information should help doctors choose the appropriate treatment for high blood pressure or heart disease in people taking PIs.
Detailed description
Ischemic cardiovascular disease and hypertension occur in persons with HIV infection, and the incidence and prevalence may increase over time as the infected population ages. Standard pharmacologic interventions for these illnesses often include calcium channel blockers (CCBs). Many of the calcium channel blockers are metabolized by cytochrome P450 3A4 (CYP 3A4), which is inhibited by some protease inhibitors (PIs). Thus, there is potential for clinically significant interactions between CCBs and PIs. The presence of significant drug-drug interactions may influence the dosing, monitoring, and choosing of CCBs and/or PIs when used in persons with HIV infection. Because of the potential concomitant use of CCBs with the PI combination IDV/RTV, this study will evaluate bi-directional drug-drug interactions between 2 commonly used CCBs and IDV/RTV. This information should assist clinicians in choosing the appropriate CCBs to treat hypertension or cardiovascular disease in persons taking PIs.
Patients are randomized to 1 of the following 2 arms:
Arm A: diltiazem CD interaction with IDV and RTV. Arm B: amlodipine interaction with IDV and RTV. From Days 1 to 7, patients take diltiazem CD (Arm A) or amlodipine (Arm B). Plasma is collected for PK over a 24-hour period beginning on Day 7. From Days 8 to 19, patients stop taking their assigned CCB and take IDV and RTV. Plasma is collected for PK over a 12-hour period on Day 19. From Days 20 to 26, patients continue to take IDV and RTV and add diltiazem CD (Arm A) or amlodipine (Arm B). Patients stop all 3 drugs after the last dose on Day 26. Plasma is collected for PK for a 24-hour period beginning on Day 26. Blood work, liver and kidney function tests, urinalysis, and an electrocardiogram (EKG) are performed at some visits.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Are HIV-negative.
- Are between the ages of 18 and 60.
- Agree not to become pregnant or to impregnate and to use an acceptable form of contraception while receiving study drugs and for 1 month after stopping study drugs. Patients who are not of reproductive potential are eligible without the contraception requirement.
- Are within 30 percent of ideal body weight.
- Weigh at least 110 lbs.
Key exclusion criteria (12 listed)
- Have a history of any illness that requires current medical therapy.
- Have a history of any kidney disorder.
- Have any medical condition that, in the opinion of the investigator, would interfere with the study.
- Are pregnant or breast-feeding.
- Use certain drugs within 14 days prior to study entry.
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 |
|---|---|---|
| Indinavir sulfate | Drug | – |
| Ritonavir | Drug | – |
| Amlodipine | Drug | – |
| Diltiazem HCl | 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 1 Nov 2021.
- Background: PubMed 9637579Yunis NA, Stone VE. Cardiac manifestations of HIV/AIDS: a review of disease spectrum and clinical management. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jun 1;18(2):145-54. doi: 10.1097/00042560-199806010-00006.
- Background: PubMed 9643798Henry K, Melroe H, Huebsch J, Hermundson J, Levine C, Swensen L, Daley J. Severe premature coronary artery disease with protease inhibitors. Lancet. 1998 May 2;351(9112):1328. doi: 10.1016/S0140-6736(05)79053-X. No abstract available.
- Background: PubMed 11371700Cattelan AM, Trevenzoli M, Sasset L, Rinaldi L, Balasso V, Cadrobbi P. Indinavir and systemic hypertension. AIDS. 2001 Apr 13;15(6):805-7. doi: 10.1097/00002030-200104130-00021. No abstract available.
- Background: PubMed 11017831Passalaris JD, Sepkowitz KA, Glesby MJ. Coronary artery disease and human immunodeficiency virus infection. Clin Infect Dis. 2000 Sep;31(3):787-97. doi: 10.1086/313995. Epub 2000 Oct 4.
- Results publication: PubMed 16084849Glesby MJ, Aberg JA, Kendall MA, Fichtenbaum CJ, Hafner R, Hall S, Grosskopf N, Zolopa AR, Gerber JG; Adult AIDS Clinical Trials Group A5159 Protocol Team. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clin Pharmacol Ther. 2005 Aug;78(2):143-53. doi: 10.1016/j.clpt.2005.04.005.
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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.
Marshall Glesby study chair
9 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 Indinavir sulfate, Ritonavir and Amlodipine in people with HIV Infections and Cardiovascular Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 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 6 inclusion and 12 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 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 NCT00039975, which also lists 5 linked publications.
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 1 Nov 2021.