Optimization of Darunavir Therapy and Dosage Recommendations
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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
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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).
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Intensive sampling : Eight blood samples collected over six hours in a subset of twelve individuals (during an additional observation period, months 19-22).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Darunavir All patients treated with darunavir |
Drug: 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:
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Outcome Measures
Primary Outcome Measures
- 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 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 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 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
- Frequency of adverse events/laboratory abnormalities [Up to 18 months]
Assessment of the frequency of adverse events or laboratory abnormalities
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Capable of giving informed consent
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HIV-positive
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Routinely followed at the Cliniques universitaires Saint-Luc
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cliniques universitaires Saint-Luc | Brussels | Belgium | 1200 |
Sponsors and Collaborators
- Université Catholique de Louvain
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
- Principal Investigator: Leila Belkhir, MD, Cliniques universitaires Saint-Luc
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UCL-LB-02