AIDS-related Dementia ComplexPhase 4NCT02503462
Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals
A Phase 4 study testing Darunavir, ritonavir and cobicistat in people with AIDS-related Dementia Complex, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
The purpose of this study is to assess whether a boosting by cobicistat results in similar concentrations of darunavir in the brain compared to a boosting by ritonavir. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AIDS-related Dementia Complex
- What is being tested?
- Darunavir, ritonavir and cobicistat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jul 2015to Jan 2017
- 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
- documented HIV infection
- presence of HIV associated neurocognitive disorders requiring a lumbar puncture for clinical reasons
- treatment or qualifying to be treated with a HIV therapy including darunavir/r (800/100 mg once daily)
- ability to comply with the study requirements
- informed consent
Who cannot join
- conditions which disrupt the blood-brain barrier and thereby impact the entry of drugs in the brain (meningitis, meningoencephalitis, multiple sclerosis, progressive multifocal leucoencephalopathy)
- co-medications inhibiting/inducing P-glycoprotein and BCRP
- co-medications inhibiting/inducing cytochrome P450 isoenzyme 3A4 (CYP3A4)
- non adherence to Treatment
- pregnancy
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Division of Infectious Diseases, University Hospital Basel
Basel, Canton of Basel-City, 4031
About this study
The purpose of this study is to assess whether a boosting by cobicistat results in similar concentrations of darunavir in the brain compared to a boosting by ritonavir.
Read the detailed description
Cobicistat is a new pharmacokinetic enhancer or booster of the HIV protease inhibitor darunavir. Cobicistat is distinct from the conventional booster ritonavir in that cobicistat presents a more selective inhibition of the enzymes metabolizing drugs. In addition, cobicistat is a weaker inhibitor of the efflux drug transporters expressed at the level of the blood-brain barrier (i.e. P-glycoprotein (P-gp) and breast cancer resistance Protein (BCRP)). A weaker inhibition of these efflux transporters could possibly result in less darunavir entering the brain when boosted by cobicistat as compared to a boosting by ritonavir. Such a difference could potentially be critical in patients with HIV-associated neurocognitive disorders as sufficient drug levels are needed to efficiently inhibit HIV replication inside the brain.
The aim of this study is to determine whether the boosting of darunavir by cobicistat results effectively in lower darunavir concentrations in the CSF as compared to a boosting by ritonavir. The study will be performed in HIV infected patients presenting HIV associated neurocognitive disorders (HAND) and requiring a lumbar puncture for clinical reasons. In addition, the patients will be only eligible if the are treated or if they qualify for a darunavir/ritonavir (800/100 mg once daily) containing regimen. Darunavir concentrations will be measured simultaneously in the CSF and plasma (CSF/plasma ratio) first with the ritonavir boosting and subsequently with the cobicistat boosting.
- Conditions
- AIDS-related Dementia Complex
- Being tested
- Darunavir, ritonavir, cobicistat
- Keywords
- HIV, darunavir, ritonavir, cobicistat, CSF, pharmacokinetics
- Medical subject headings
- AIDS Dementia Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarunavirDrug
Also called Prezista
darunavir 800 mg once daily will be first given together with ritonavir 100 mg once daily for one month (period 1) and then darunavir 800 mg once daily will be given together with cobicistat 150 mg once daily for one month (period 2). Afterwards, all patients will be switched back to darunavir/ritonavir (800/100 mg once daily).
ritonavirDrug
Also called Norvir
ritonavir 100 mg once daily will be used to boost darunavir 800 mg once daily (period 1).
cobicistatDrug
Also called Tybost
cobicistat 150 mg once daily will be used to boost darunavir 800 mg once daily (period 2).
| Study group | Role | What they receive |
|---|---|---|
| darunavir/ritonavir vs cobicistat | Experimental | All HIV infected patients will be treated with a darunavir/ritonavir (800/100 mg) once daily containing regimen. Darunavir/ritonavir concentrations will be measured simultaneously in CSF and plasma after 1 month of treatment. The treatment will be switched to darunavir/cobicistat (800/150 mg) once daily and darunavir/cobicistat levels will be measured in CSF and plasma after 1 month of treatment. Receives: Drug: Darunavir; Drug: ritonavir; Drug: cobicistat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebrospinal fluid/plasma concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat
darunavir concentrations (ng/ml) in the cerebrospinal fluid when coadministered with ritonavir versus cobicistat relative to the corresponding concentrations of darunavir in the plasma
Measured: 1 month
Secondary outcomes (2)
Cerebrospinal fluid concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat relative to the concentration of darunavir (ng/ml) inhibiting 50% (IC50) or 90% (IC90) of the viral replication
darunavir concentrations (ng/ml) in the cerebrospinal fluid when coadministered with ritonavir versus cobicistat relative to darunavir concentrations (ng/ml) suppressing HIV replication by 50% and 90% (IC50 and IC90)
Measured: 1 month
Proportion of responders (HIV RNA < 50 copies/ml in CSF) for darunavir/ritonavir versus darunavir/cobicistat
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionJan 2017
- Study completionJan 2017
Why it stopped: No additional patients fulfilling the inclusion criteria
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 AIDS-related Dementia ComplexStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manuel Battegay, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503462
- Sponsor's protocol ID
- DRVCOBI
- Status last verified
- Feb 2017
- First submitted
- 9 Jul 2015
- Last updated
- 2 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Bartels H, Decosterd L, Battegay M, Marzolini C. Darunavir concentrations in CSF of HIV-infected individuals when boosted with cobicistat versus ritonavir. J Antimicrob Chemother. 2017 Sep 1;72(9):2574-2577. doi: 10.1093/jac/dkx165.
PubMed 28575323
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals
- ClinicalTrials.gov ID
- NCT02503462
- Acronym / sponsor ID
- DRVCOBI
- Conditions
- AIDS-related Dementia Complex
- Keywords
- HIV, darunavir, ritonavir, cobicistat, CSF, pharmacokinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No additional patients fulfilling the inclusion criteria
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 21 Jul 2015 (estimated)
- 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.
The purpose of this study is to assess whether a boosting by cobicistat results in similar concentrations of darunavir in the brain compared to a boosting by ritonavir.
Detailed description
Cobicistat is a new pharmacokinetic enhancer or booster of the HIV protease inhibitor darunavir. Cobicistat is distinct from the conventional booster ritonavir in that cobicistat presents a more selective inhibition of the enzymes metabolizing drugs. In addition, cobicistat is a weaker inhibitor of the efflux drug transporters expressed at the level of the blood-brain barrier (i.e. P-glycoprotein (P-gp) and breast cancer resistance Protein (BCRP)). A weaker inhibition of these efflux transporters could possibly result in less darunavir entering the brain when boosted by cobicistat as compared to a boosting by ritonavir. Such a difference could potentially be critical in patients with HIV-associated neurocognitive disorders as sufficient drug levels are needed to efficiently inhibit HIV replication inside the brain.
The aim of this study is to determine whether the boosting of darunavir by cobicistat results effectively in lower darunavir concentrations in the CSF as compared to a boosting by ritonavir. The study will be performed in HIV infected patients presenting HIV associated neurocognitive disorders (HAND) and requiring a lumbar puncture for clinical reasons. In addition, the patients will be only eligible if the are treated or if they qualify for a darunavir/ritonavir (800/100 mg once daily) containing regimen. Darunavir concentrations will be measured simultaneously in the CSF and plasma (CSF/plasma ratio) first with the ritonavir boosting and subsequently with the cobicistat boosting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| darunavir/ritonavir vs cobicistat | Experimental | Drug: Darunavir, Drug: ritonavir, Drug: cobicistatAll HIV infected patients will be treated with a darunavir/ritonavir (800/100 mg) once daily containing regimen. Darunavir/ritonavir concentrations will be measured simultaneously in CSF and plasma after 1 month of treatment. The treatment will be switched to darunavir/cobicistat (800/150 mg) once daily and darunavir/cobicistat levels will be measured in CSF and plasma after 1 month of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- documented HIV infection
- presence of HIV associated neurocognitive disorders requiring a lumbar puncture for clinical reasons
- treatment or qualifying to be treated with a HIV therapy including darunavir/r (800/100 mg once daily)
- ability to comply with the study requirements
- informed consent
Key exclusion criteria (5 listed)
- conditions which disrupt the blood-brain barrier and thereby impact the entry of drugs in the brain (meningitis, meningoencephalitis, multiple sclerosis, progressive multifocal leucoencephalopathy)
- co-medications inhibiting/inducing P-glycoprotein and BCRP
- co-medications inhibiting/inducing cytochrome P450 isoenzyme 3A4 (CYP3A4)
- non adherence to Treatment
- pregnancy
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: Prezistadarunavir 800 mg once daily will be first given together with ritonavir 100 mg once daily for one month (period 1) and then darunavir 800 mg once daily will be given together with cobicistat 150 mg once daily for one month (period 2). Afterwards, all patients will be switched back to darunavir/ritonavir (800/100 mg once daily). | Drug | darunavir/ritonavir vs cobicistat |
| ritonavirAlso: Norvirritonavir 100 mg once daily will be used to boost darunavir 800 mg once daily (period 1). | Drug | darunavir/ritonavir vs cobicistat |
| cobicistatAlso: Tybostcobicistat 150 mg once daily will be used to boost darunavir 800 mg once daily (period 2). | Drug | darunavir/ritonavir vs cobicistat |
Primary outcome
Cerebrospinal fluid/plasma concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat
Time frame: 1 month
darunavir concentrations (ng/ml) in the cerebrospinal fluid when coadministered with ritonavir versus cobicistat relative to the corresponding concentrations of darunavir in the plasma
2 secondary outcomes
Cerebrospinal fluid concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat relative to the concentration of darunavir (ng/ml) inhibiting 50% (IC50) or 90% (IC90) of the viral replication
Time frame: 1 month
Proportion of responders (HIV RNA < 50 copies/ml in CSF) for darunavir/ritonavir versus darunavir/cobicistat
Time frame: 1 month
Results and safety
The study was stopped early (reason given: No additional patients fulfilling the inclusion criteria). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2017.
- Derived from this study: PubMed 28575323Bartels H, Decosterd L, Battegay M, Marzolini C. Darunavir concentrations in CSF of HIV-infected individuals when boosted with cobicistat versus ritonavir. J Antimicrob Chemother. 2017 Sep 1;72(9):2574-2577. doi: 10.1093/jac/dkx165.
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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.
Manuel Battegay principal investigator
University Hospital, Basel, Switzerland
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, ritonavir and cobicistat in people with AIDS-related Dementia Complex, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 5 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: stopped early, as of the sponsor's last update on 2 Feb 2017. 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 Switzerland. 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 was stopped early (reason given: No additional patients fulfilling the inclusion criteria). Results are not available in the source record.
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?
Cerebrospinal fluid/plasma concentrations (ng/ml) of darunavir/ritonavir versus darunavir/cobicistat (time frame: 1 month). 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 NCT02503462, 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 2 Feb 2017.