Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00039975
First received: June 18, 2002
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Cardiovascular Diseases
Hypertension
Drug: Indinavir sulfate
Drug: Ritonavir
Drug: Amlodipine
Drug: Diltiazem HCl
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Potential Pharmacokinetic Interactions Between HIV Protease Inhibitors and Calcium Channel Blockers

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 32
Study Completion Date: April 2004
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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00039975

Locations
United States, California
Univ of California San Francisco
San Francisco, California, United States, 94110
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington Univ (St. Louis)
St. Louis, Missouri, United States, 63108
United States, New York
Cornell Univ Med Ctr
New York, New York, United States, 10021
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Sponsors and Collaborators
Investigators
Study Chair: Marshall Glesby
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00039975     History of Changes
Other Study ID Numbers: A5159, 10959, ACTG A5159, AACTG A5159
Study First Received: June 18, 2002
Last Updated: May 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Interactions
HIV Protease Inhibitors
Ritonavir
Indinavir
Calcium Channel Blockers
Pharmacokinetics
Diltiazem
Amlodipine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Cardiovascular Diseases
Hypertension
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Vascular Diseases
Calcium Channel Blockers
Diltiazem
Amlodipine
Protease Inhibitors
Indinavir
Ritonavir
HIV Protease Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents
Enzyme Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 18, 2014