NCT02503462

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

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
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).
DRUG	ritonavir	ritonavir 100 mg once daily will be used to boost darunavir 800 mg once daily (period 1).
DRUG	cobicistat	cobicistat 150 mg once daily will be used to boost darunavir 800 mg once daily (period 2).

Timeline

• Start date: 2015-07-01
• Primary completion: 2017-01-01
• Completion: 2017-01-01
• First posted: 2015-07-21
• Last updated: 2017-02-02

Locations

1 site across 1 country: Switzerland