Human Immunodeficiency Virus I InfectionPhase 4NCT03101644
Optimization of Darunavir Therapy and Dosage Recommendations
A Phase 4 study testing Darunavir in people with Human Immunodeficiency Virus I Infection, run by Université Catholique de Louvain at 1 site in Belgium.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Immunodeficiency Virus I Infection
- What is being tested?
- Darunavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteBelgium
- Study dates
- 23 Mar 2017to 12 Jun 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving informed consent
- HIV-positive
- Routinely followed at the Cliniques universitaires Saint-Luc
- Treated with darunavir
- Perfect adherence to treatment (as assessed by anamnesis and based on available PK data for each patient)
Who cannot join
- N/A
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimization of Darunavir Therapy Through Population Pharmacokinetic Modeling, Simulations and Dosage Guidelines
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.
Read the 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).
- Conditions
- Human Immunodeficiency Virus I Infection
- Being tested
- Darunavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarunavirDrug
Also called Prezista, Rezolsta
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)
| Study group | Role | What they receive |
|---|---|---|
| Darunavir | Other | All patients treated with darunavir Receives: Drug: Darunavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Darunavir clearance
Assessment of darunavir whole-body clearance and inter-compartmental clearance through population pharmacokinetic methods
Measured: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir volume of distribution
Assessment of darunavir volume of distribution through population pharmacokinetic methods
Measured: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir absorption rate
Assessment of darunavir absorption rate through population pharmacokinetic methods
Measured: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir area under the concentration-time curve (AUC)
Assessment of darunavir area under the concentration-time curve through population pharmacokinetic methods
Measured: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Darunavir maximum plasma concentration (Cmax)
Assessment of darunavir maximum plasma concentration through population pharmacokinetic methods
Measured: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Secondary outcomes (4)
Frequency of adverse events/laboratory abnormalities
Assessment of the frequency of adverse events or laboratory abnormalities
Measured: Up to 18 months
Change in viral load
Assessment of the change in viral load (HIV copies/ml of blood)
Measured: Up to 18 months
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
Assessment of the change in blood CD4+ T lymphocyte count
Measured: Up to 18 months
Ritonavir/cobicistat AUC
Assessment of the pharmacokinetic booster (either ritonavir or cobicistat, depending on the subject) AUC through population pharmacokinetic methods
Measured: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study start23 Mar 2017
- Primary completion12 Jun 2019
- Study completion12 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency Virus I InfectionStudies of the same condition, open and under way.
- More trials run by Université Catholique de LouvainThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université Catholique de Louvain
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laure Elens, Université Catholique de Louvain
- Investigators
- Leila Belkhir, MD, Principal investigator, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101644
- Sponsor's protocol ID
- UCL-LB-02
- Status last verified
- Aug 2019
- First submitted
- 23 Mar 2017
- Last updated
- 3 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32696441
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Darunavir Therapy Through Population Pharmacokinetic Modeling, Simulations and Dosage Guidelines
- ClinicalTrials.gov ID
- NCT03101644
- Acronym / sponsor ID
- UCL-LB-02
- Conditions
- Human Immunodeficiency Virus I Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Université Catholique de LouvainUniversity, hospital or other
- Collaborators
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Study start
- 23 Mar 2017 (actual)
- Primary completion
- 12 Jun 2019 (actual)
- Study completion
- 12 Jun 2019 (actual)
- First posted
- 5 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Darunavir | Other | Drug: DarunavirAll patients treated with darunavir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Capable of giving informed consent
- HIV-positive
- Routinely followed at the Cliniques universitaires Saint-Luc
- Treated with darunavir
- Perfect adherence to treatment (as assessed by anamnesis and based on available PK data for each patient)
Key exclusion criteria (1 listed)
- N/A
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DarunavirAlso: Prezista, RezolstaThe investigated drugs are Prezista (darunavir 600 mg twice-daily or 800 mg once-daily) and Rezolsta (darunavir 800 mg/cobicistat 150 mg once-daily) | Drug | Darunavir |
Primary outcome
Darunavir clearance
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
4 secondary outcomes
Frequency of adverse events/laboratory abnormalities
Time frame: Up to 18 months
Change in viral load
Time frame: Up to 18 months
Change in blood Cluster of Differentiation 4 (CD4+) T lymphocyte count
Time frame: Up to 18 months
Ritonavir/cobicistat AUC
Time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2019.
- Derived from this study: PubMed 32696441Stillemans 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leila Belkhir, MD principal investigator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Darunavir in people with Human Immunodeficiency Virus I Infection, run by Université Catholique de Louvain at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Darunavir clearance (time frame: Up to 18 months (blood sampling for PK once at each visit, three visits per patient over the study period)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03101644, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2019.