Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers

NCT ID: NCT00039975

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2004-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections Cardiovascular Diseases Hypertension

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Drug Interactions HIV Protease Inhibitors Ritonavir Indinavir Calcium Channel Blockers Pharmacokinetics Diltiazem Amlodipine

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Indinavir sulfate

Intervention Type DRUG

Ritonavir

Intervention Type DRUG

Amlodipine

Intervention Type DRUG

Diltiazem HCl

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Marshall Glesby

Role: STUDY_CHAIR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Univ of California San Francisco

San Francisco, California, United States

Site Status

Stanford Univ Med Ctr

Stanford, California, United States

Site Status

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Site Status

Johns Hopkins Hosp

Baltimore, Maryland, United States

Site Status

Univ of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington Univ (St. Louis)

St Louis, Missouri, United States

Site Status

Cornell Univ Med Ctr

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

Univ of Cincinnati

Cincinnati, Ohio, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 9637579 (View on PubMed)

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. doi: 10.1016/S0140-6736(05)79053-X. No abstract available.

Reference Type BACKGROUND
PMID: 9643798 (View on PubMed)

Cattelan 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.

Reference Type BACKGROUND
PMID: 11371700 (View on PubMed)

Passalaris 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.

Reference Type BACKGROUND
PMID: 11017831 (View on PubMed)

Glesby 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.

Reference Type RESULT
PMID: 16084849 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

10959

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5159

Identifier Type: -

Identifier Source: secondary_id

AACTG A5159

Identifier Type: -

Identifier Source: secondary_id

A5159

Identifier Type: -

Identifier Source: org_study_id