Tenofovir, Emtricitabine, Efavirenz and Atazanavir Pharmacokinetics in the Aging HIV-Infected Population

This study is currently recruiting participants.
Verified April 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Julie Dumond, PharmD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01180075
First received: August 10, 2010
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

Purpose: To see how growing older changes the amount of HIV drugs in the blood of HIV-infected men and women. Many changes happen in the body as it ages that may affect the way drugs are carried in the blood, broken down or removed from the body. This study will look at the amount of drug in the blood and cells of the immune system for patients taking efavirenz, tenofovir and emtricitabine or atazanavir boosted with ritonavir, tenofovir and emtricitabine.

Participants: The population will comprise of 56 (6 for intensive PK and 50 for sparse sampling) HIV-infected adults currently adhering to an antiretroviral regimen containing efavirenz with tenofovir and emtricitabine and the same number and distribution of HIV-infected adults currently adhering to an antiretroviral regimen containing atazanavir boosted with ritonavir with tenofovir and emtricitabine.

Procedures (methods): This study will be completed at the University of North Carolina at Chapel Hill. There will be four groups of subjects: Efavirenz/tenofovir/emtricitabine Group A, Efavirenz/tenofovir/emtricitabine Group B, Atazanavir/ritonavir/tenofovir/emtricitabine Group A, and Atazanavir/ritonavir/tenofovir/emtricitabine Group B.

The initial six subjects (Group A) for intensive PK analysis for each regimen will be recruited from the the UNC ID Clinic or the Moses Cone Health System Infectious Diseases Clinic, and will be comprised of non-frail subjects not currently receiving interacting drugs. If subjects provide informed consent, timed blood samples will be obtained to determine pharmacokinetic parameters around an observed dose of one of the two study regimens. A whole blood sample will also be collected and stored for potential drug metabolizing enzymes and transporters genotyping in the future. Group A subjects will complete a follow-up visit after their sampling visit.

50 subsequent subjects (Group B) for each regimen will be screened simultaneously, with no more than 10 subjects enrolled for each regimen in Group B prior to the completion and analysis of Group A. These subjects will also be recruited from either site. Group B subjects will have one or two sampling visits with 1 to 4 blood samples obtained at each visit, with a stored sample for future genotyping obtained on one of the visits. Samples will be collected just prior to a dose, at 2 hours, between 4 and 6 hrs, and between 10 and 14 hours after a medication dose. These visits may coincide with the subjects' regularly scheduled visit to the clinic, or be scheduled separately, depending on the preference and availability of the subject.


Condition Intervention
Human Immunodeficiency Virus
Drug: tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)
Drug: tenofovir/emtricitabine (TDF/FTC)
Drug: Atazanavir (ATV)
Drug: Ritonavir
Procedure: Phlebotomy

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Tenofovir, Emtricitabine, Efavirenz and Atazanavir Pharmacokinetics in the Aging HIV-Infected Population

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Clearance estimates for each drug, adjusted for age and frailty [ Time Frame: From 0, 2, 4-6, and 10-14 hr post-dose blood samples ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood samples for determining drug concentrations and for future genetic testing of drug metabolizing enzymes and transporters will be stored for up to 5 years.


Estimated Enrollment: 112
Study Start Date: May 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
TDF/FTC/EFV Intensive Sampling-Group A
Patients receiving TDF/FTC/EFV who undergo intensive pharmacokinetic sampling over 24 hours
Drug: tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)
Patients receiving this drug for clinical care at standard dosages will be enrolled.
Other Name: Atripla
Procedure: Phlebotomy
Multiple blood draws will be performed in the study, and vary depending on the group.
TDF/FTC/ATV/r Intensive Sampling Group A
Patients receiving TDF/FTC/ATV/r who undergo intensive pharmacokinetic sampling over 24 hours
Drug: tenofovir/emtricitabine (TDF/FTC)
Patients receiving this drug for clinical care at standard dosages will be enrolled.
Other Name: Truvada
Drug: Atazanavir (ATV)
Patients receiving this drug for clinical care at 300mg with 100mg ritonavir daily will be enrolled.
Other Name: Reyataz
Drug: Ritonavir
Patients receiving this drug for clinical care at 100mg daily with 300mg atazanavir will be enrolled.
Other Name: Norvir
Procedure: Phlebotomy
Multiple blood draws will be performed in the study, and vary depending on the group.
TDF/FTC/EFV Sparse Sampling Group B
Patients receiving TDF/FTC/EFV who undergo sparse pharmacokinetic sampling on 1 or 2 visits depending on subject's availability
Drug: tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV)
Patients receiving this drug for clinical care at standard dosages will be enrolled.
Other Name: Atripla
Procedure: Phlebotomy
Multiple blood draws will be performed in the study, and vary depending on the group.
TDF/FTC/ATV/r Sparse Sampling Group B
Patients receiving TDF/FTC/ATV/r who undergo sparse pharmacokinetic sampling on 1 or 2 visits depending on subject's availability
Drug: tenofovir/emtricitabine (TDF/FTC)
Patients receiving this drug for clinical care at standard dosages will be enrolled.
Other Name: Truvada
Drug: Atazanavir (ATV)
Patients receiving this drug for clinical care at 300mg with 100mg ritonavir daily will be enrolled.
Other Name: Reyataz
Drug: Ritonavir
Patients receiving this drug for clinical care at 100mg daily with 300mg atazanavir will be enrolled.
Other Name: Norvir
Procedure: Phlebotomy
Multiple blood draws will be performed in the study, and vary depending on the group.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV Positive patients on a stable regimen consisting of either efavirenz/tenofovir/emtricitabine or atazanavir boosted with ritonavir/tenofovir/emtricitabine

Criteria

Inclusion Criteria:

  • HIV positive patients
  • Able to provide written informed consent
  • Able to comply with their treatment regimen and study procedures
  • Currently receiving either efavirenz/tenofovir/emtricitabine or atazanavir/ritonavir/tenofovir/emtricitabine as treatment for their HIV infection. Subjects must have been on the regimen for at least 2 weeks
  • All women of reproductive potential must have a negative urine pregnancy test
  • If participating in sexual activity that could lead to pregnancy, study participant must use at least one reliable method of contraception.

Exclusion Criteria:

  • Displaying the fraility phenotype (Group A only)
  • Receiving an interacting medication
  • Having missed >3 doses of study medication in the past 30 days
  • Patients who will not likely remain on the study regimen during the course of study participation.
  • Anemia (hemoglobin <10 g/dL)
  • Abnormal screening laboratory findings
  • Pregnancy
  • Breastfeeding
  • Any condition that may interfere with follow-up or the ability to take the study medication appropriately.
  • Any clinically significant surgical alterations of the alimentary track, that in the opinion of the investigators, alters the absorption pharmacokinetics of the drugs of interest.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01180075

Contacts
Contact: Julie B Dumond, PharmD 919-966-5017 jdumond@unc.edu
Contact: Heather Prince, PA-C 919-843-6848 heather_prince@med.unc.edu

Locations
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Principal Investigator: Julie B Dumond, PharmD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Julie B Dumond, PharmD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Julie Dumond, PharmD, Assistant Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01180075     History of Changes
Other Study ID Numbers: 09-2120, 1K23AI093156-01A1
Study First Received: August 10, 2010
Last Updated: April 3, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Atazanavir
Tenofovir
Tenofovir disoproxil
Efavirenz
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014