Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Cardiovascular Diseases; Hypertension
Intervention: Indinavir sulfate (Drug); Ritonavir (Drug); Amlodipine (Drug); Diltiazem HCl (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Marshall Glesby, Study Chair
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.
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.
Clinical Details
Official title: Evaluation of Potential Pharmacokinetic Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers
Study design: Endpoint Classification: Safety/Efficacy Study, Masking: Open Label, Primary Purpose: Treatment
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria
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.
Exclusion Criteria
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.
- 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.
Locations and Contacts
Univ of California San Francisco, San Francisco, California 94110, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
Washington Univ (St. Louis), St. Louis, Missouri 63108, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Additional Information
Click here for more information about indinavir sulfate Click here for more information about ritonavir Haga clic aquí para ver información sobre este ensayo clínico en español.
Related 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. Review. Henry 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. Cattelan AM, Trevenzoli M, Sasset L, Rinaldi L, Balasso V, Cadrobbi P. Indinavir and systemic hypertension. AIDS. 2001 Apr 13;15(6):805-7. Passalaris JD, Sepkowitz KA, Glesby MJ. Coronary artery disease and human immunodeficiency virus infection. Clin Infect Dis. 2000 Sep;31(3):787-97. Epub 2000 Oct 4. Review.
Last updated: May 17, 2012
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