Optimization of Darunavir Therapy and Dosage Recommendations

Human Immunodeficiency Virus I Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03101644
• Other study ID #: UCL-LB-02
• Status: Completed
• Phase: Phase 4
• Start date: March 23, 2017
• Est. completion date: June 12, 2019

Study information

• Verified date: August 2019
• Source: Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: June 12, 2019
• Est. primary completion date: June 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus I Infection

Intervention

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)

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Université Catholique de Louvain	Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Darunavir clearance	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)
Primary	Darunavir volume of distribution	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)
Primary	Darunavir absorption rate	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)
Primary	Darunavir area under the concentration-time curve (AUC)	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)
Primary	Darunavir maximum plasma concentration (Cmax)	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	Frequency of adverse events/laboratory abnormalities	Assessment of the frequency of adverse events or laboratory abnormalities	Up to 18 months
Secondary	Change in viral load	Assessment of the change in viral load (HIV copies/ml of blood)	Up to 18 months
Secondary	Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count	Assessment of the change in blood CD4+ T lymphocyte count	Up to 18 months
Secondary	Ritonavir/cobicistat AUC	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)