Optimization of Darunavir Therapy and Dosage Recommendations
Primary Purpose
Human Immunodeficiency Virus I Infection
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Darunavir
Sponsored by
About this trial
This is an interventional other trial for Human Immunodeficiency Virus I Infection
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
Sites / Locations
- Cliniques universitaires Saint-Luc
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Darunavir
Arm Description
All patients treated with darunavir
Outcomes
Primary Outcome Measures
Darunavir clearance
Assessment of darunavir whole-body clearance and inter-compartmental clearance through population pharmacokinetic methods
Darunavir volume of distribution
Assessment of darunavir volume of distribution through population pharmacokinetic methods
Darunavir absorption rate
Assessment of darunavir absorption rate through population pharmacokinetic methods
Darunavir area under the concentration-time curve (AUC)
Assessment of darunavir area under the concentration-time curve through population pharmacokinetic methods
Darunavir maximum plasma concentration (Cmax)
Assessment of darunavir maximum plasma concentration through population pharmacokinetic methods
Secondary Outcome Measures
Frequency of adverse events/laboratory abnormalities
Assessment of the frequency of adverse events or laboratory abnormalities
Change in viral load
Assessment of the change in viral load (HIV copies/ml of blood)
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
Assessment of the change in blood CD4+ T lymphocyte count
Ritonavir/cobicistat AUC
Assessment of the pharmacokinetic booster (either ritonavir or cobicistat, depending on the subject) AUC through population pharmacokinetic methods
Full Information
NCT ID
NCT03101644
First Posted
March 23, 2017
Last Updated
August 30, 2019
Sponsor
Université Catholique de Louvain
Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
1. Study Identification
Unique Protocol Identification Number
NCT03101644
Brief Title
Optimization of Darunavir Therapy and Dosage Recommendations
Official Title
Optimization of Darunavir Therapy Through Population Pharmacokinetic Modeling, Simulations and Dosage Guidelines
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
March 23, 2017 (Actual)
Primary Completion Date
June 12, 2019 (Actual)
Study Completion Date
June 12, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Université Catholique de Louvain
Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
4. Oversight
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
Data Monitoring Committee
No
5. 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus I Infection
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
127 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Darunavir
Arm Type
Other
Arm Description
All patients treated with darunavir
Intervention Type
Drug
Intervention Name(s)
Darunavir
Other Intervention Name(s)
Prezista, Rezolsta
Intervention Description
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)
Primary Outcome Measure Information:
Title
Darunavir clearance
Description
Assessment of darunavir whole-body clearance and inter-compartmental clearance through population pharmacokinetic methods
Time Frame
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Title
Darunavir volume of distribution
Description
Assessment of darunavir volume of distribution through population pharmacokinetic methods
Time Frame
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Title
Darunavir absorption rate
Description
Assessment of darunavir absorption rate through population pharmacokinetic methods
Time Frame
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Title
Darunavir area under the concentration-time curve (AUC)
Description
Assessment of darunavir area under the concentration-time curve through population pharmacokinetic methods
Time Frame
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Title
Darunavir maximum plasma concentration (Cmax)
Description
Assessment of darunavir maximum plasma concentration through population pharmacokinetic methods
Time Frame
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Secondary Outcome Measure Information:
Title
Frequency of adverse events/laboratory abnormalities
Description
Assessment of the frequency of adverse events or laboratory abnormalities
Time Frame
Up to 18 months
Title
Change in viral load
Description
Assessment of the change in viral load (HIV copies/ml of blood)
Time Frame
Up to 18 months
Title
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
Description
Assessment of the change in blood CD4+ T lymphocyte count
Time Frame
Up to 18 months
Title
Ritonavir/cobicistat AUC
Description
Assessment of the pharmacokinetic booster (either ritonavir or cobicistat, depending on the subject) AUC through population pharmacokinetic methods
Time Frame
Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leila Belkhir, MD
Organizational Affiliation
Cliniques universitaires Saint-Luc
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cliniques universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32696441
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.
Results Reference
derived
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Optimization of Darunavir Therapy and Dosage Recommendations
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