Clinical trial NCT03101644: Optimization of Darunavir Therapy and Dosage Recommendations
Official title: Optimization of Darunavir Therapy Through Population Pharmacokinetic Modeling, Simulations and Dosage Guidelines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus I Infection
Lead sponsor: Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
First posted: 2017-04-05
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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).

Eligibility criteria: 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

Primary outcomes:
measure: Darunavir clearance
timeFrame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
measure: Darunavir volume of distribution
timeFrame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
measure: Darunavir absorption rate
timeFrame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
measure: Darunavir area under the concentration-time curve (AUC)
timeFrame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
measure: Darunavir maximum plasma concentration (Cmax)
timeFrame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Secondary outcomes:
measure: Frequency of adverse events/laboratory abnormalities
timeFrame: Up to 18 months
measure: Change in viral load
timeFrame: Up to 18 months
measure: Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
timeFrame: Up to 18 months
measure: Ritonavir/cobicistat AUC
timeFrame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Leila Belkhir, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stillemans G, Belkhir L, Vandercam B, Vincent A, Haufroid V, Elens L. Exploration of Reduced Doses and Short-Cycle Therapy for Darunavir/Cobicistat in Patients with HIV Using Population Pharmacokinetic Modeling and Simulations. Clin Pharmacokinet. 2021 Feb;60(2):177-189. doi: 10.1007/s40262-020-00920-z.