Optimization of Darunavir Therapy and Dosage Recommendations
- Registration Number
- NCT03101644
- Lead Sponsor
- Université Catholique de Louvain
- Brief Summary
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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 127
- 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)
- N/A
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Darunavir Darunavir All patients treated with darunavir
- Primary Outcome Measures
Name Time Method Darunavir clearance 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
Darunavir absorption rate 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
Darunavir volume of distribution 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
Darunavir area under the concentration-time curve (AUC) 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
Darunavir maximum plasma concentration (Cmax) 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
- Secondary Outcome Measures
Name Time Method Change in viral load Up to 18 months Assessment of the change in viral load (HIV copies/ml of blood)
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count Up to 18 months Assessment of the change in blood CD4+ T lymphocyte count
Ritonavir/cobicistat AUC 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
Frequency of adverse events/laboratory abnormalities Up to 18 months Assessment of the frequency of adverse events or laboratory abnormalities
Trial Locations
- Locations (1)
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Belgium