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Trial record 3 of 108 for:    HIV AND GS9350

Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals

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ClinicalTrials.gov Identifier: NCT02503462
Recruitment Status : Terminated (No additional patients fulfilling the inclusion criteria)
First Posted : July 21, 2015
Last Update Posted : February 2, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief 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.

Condition or disease Intervention/treatment Phase
AIDS-related Dementia Complex Drug: Darunavir Drug: ritonavir Drug: cobicistat Phase 4

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Cobicistat Versus Ritonavir Boosting on the Brain Permeation of Darunavir in HIV-infected Individuals
Study Start Date : July 2015
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: darunavir/ritonavir vs cobicistat
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.
Drug: Darunavir
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).
Other Name: Prezista

Drug: ritonavir
ritonavir 100 mg once daily will be used to boost darunavir 800 mg once daily (period 1).
Other Name: Norvir

Drug: cobicistat
cobicistat 150 mg once daily will be used to boost darunavir 800 mg once daily (period 2).
Other Name: Tybost




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]
    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)

  2. Proportion of responders (HIV RNA < 50 copies/ml in CSF) for darunavir/ritonavir versus darunavir/cobicistat [ Time Frame: 1 month ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02503462


Locations
Switzerland
Division of Infectious Diseases, University Hospital Basel
Basel, BS, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Manuel Battegay University Hospital, Basel, Switzerland

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02503462     History of Changes
Other Study ID Numbers: DRVCOBI
First Posted: July 21, 2015    Key Record Dates
Last Update Posted: February 2, 2017
Last Verified: February 2017

Keywords provided by University Hospital, Basel, Switzerland:
HIV
darunavir
ritonavir
cobicistat
CSF
pharmacokinetics

Additional relevant MeSH terms:
HIV Infections
Cobicistat
HIV Protease Inhibitors
Anti-HIV Agents
Dementia
AIDS Dementia Complex
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Darunavir
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors