Optimization of Darunavir Therapy and Dosage Recommendations

August 30, 2019 updated by: Laure Elens, Université Catholique de Louvain

Optimization of Darunavir Therapy Through Population Pharmacokinetic Modeling, Simulations and Dosage Guidelines

This study will assess and characterize the variability observed in the response to darunavir therapy, an antiretroviral medication used against the Human Immunodeficiency Virus (HIV). More specifically, it aims to quantify variations in the drug's blood concentrations and determine the sources of such variability, both genetic and non-genetic. In light of this information, current dosage guidelines will then be reviewed.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Data will be used to create a population pharmacokinetic model. Inter- and intra-individual pharmacokinetic variability will be quantified and linked to patient-specific covariates, both genetic and non-genetic in nature. Pharmacokinetic-pharmacodynamic relationships will be established, linking drug exposure to efficacy (as measured by CD4 cell count and viral load reduction) and toxicity (as measured by frequency and degree of adverse events). Simulations will be conducted for specific patient profiles and current dosage guidelines reviewed.

Pharmacokinetic design : combined sparse/intensive sampling

  • Sparse sampling : One blood sample collected in each individual at a random post-intake time (during a routine visit to the hospital), up to three times over the course of the study period (months 1-18).
  • Intensive sampling : Eight blood samples collected over six hours in a subset of twelve individuals (during an additional observation period, months 19-22).

Study Type

Interventional

Enrollment (Actual)

127

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Capable of giving informed consent
  • HIV-positive
  • Routinely followed at the Cliniques universitaires Saint-Luc
  • Treated with darunavir

Inclusion Criteria (intensive sampling):

- Perfect adherence to treatment (as assessed by anamnesis and based on available PK data for each patient)

Exclusion Criteria:

- N/A

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Darunavir
All patients treated with darunavir
The investigated drugs are Prezista (darunavir 600 mg twice-daily or 800 mg once-daily) and Rezolsta (darunavir 800 mg/cobicistat 150 mg once-daily)
Other Names:
  • Prezista
  • Rezolsta

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Darunavir clearance
Time Frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Assessment of darunavir whole-body clearance and inter-compartmental clearance through population pharmacokinetic methods
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir volume of distribution
Time Frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Assessment of darunavir volume of distribution through population pharmacokinetic methods
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir absorption rate
Time Frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Assessment of darunavir absorption rate through population pharmacokinetic methods
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir area under the concentration-time curve (AUC)
Time Frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Assessment of darunavir area under the concentration-time curve through population pharmacokinetic methods
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir maximum plasma concentration (Cmax)
Time Frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Assessment of darunavir maximum plasma concentration through population pharmacokinetic methods
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events/laboratory abnormalities
Time Frame: Up to 18 months
Assessment of the frequency of adverse events or laboratory abnormalities
Up to 18 months
Change in viral load
Time Frame: Up to 18 months
Assessment of the change in viral load (HIV copies/ml of blood)
Up to 18 months
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
Time Frame: Up to 18 months
Assessment of the change in blood CD4+ T lymphocyte count
Up to 18 months
Ritonavir/cobicistat AUC
Time Frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Assessment of the pharmacokinetic booster (either ritonavir or cobicistat, depending on the subject) AUC through population pharmacokinetic methods
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Leila Belkhir, MD, Cliniques Universitaires Saint-Luc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 23, 2017

Primary Completion (ACTUAL)

June 12, 2019

Study Completion (ACTUAL)

June 12, 2019

Study Registration Dates

First Submitted

March 23, 2017

First Submitted That Met QC Criteria

March 29, 2017

First Posted (ACTUAL)

April 5, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 3, 2019

Last Update Submitted That Met QC Criteria

August 30, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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