The Rilpivirine Cerebrospinal-fluid (CSF) Study

Study Overview
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Brief Summary
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This is a phase I pharmacokinetic study of HIV positive patients stable on antiretroviral therapy who will switch treatment when enrolled from nevirapine to rilpivirine. On day 60 of the study the participants will attend clinic where they will have blood collected followed by a lumbar puncture where cerebrospinal fluid will be collected to measure drug concentration. The participants will then restart their original regime with nevirapine.

Detailed Description
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To investigate the following parameters in HIV-infected patients switching antiretroviral therapy from TDF/FTC/nevirapine to TDF/FTC/rilpivirine for 60 days: CSF exposure and CSF : plasma ratio of rilpivirine Safety and tolerability of switching antiretroviral therapy from TDF/FTC/nevirapine to TDF/FTC/rilpivirine Changes in cerebral metabolites measured via 1-H MRS after switching antiretroviral therapy to TDF/FTC/rilpivirine Seminal fluid exposure of rilpivirine

Official Title
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A Phase I Pharmacokinetic Study to Assess the Cerebrospinal-fluid (CSF) Exposure of Rilpivirine in HIV-infected Subjects Switching From TDF/FTC/Nevirapine to TDF/FTC/Rilpivirine

Conditions
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HIV

Intervention / Treatment
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* Drug: Rilpivirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected males subjects signed informed consent willing to switch therapy as per study protocol no previous exposure to rilpivirine plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over the last 3 months currently receiving a stable antiretroviral regimen comprising of TDF/FTC with nevirapine with nevirapine dosed either 200 mg twice daily or 400 mg once daily with no antiretroviral drug switches for at least 3 months no clinically-significant resistance documented on any prior HIV-1 genotypic resistance testing subjects in good health upon medical history, physical exam, and laboratory testing BMI above or equal to 18 and below 32 Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom and diaphragm) during heterosexual intercourse, from screening through completion of the study. Have local screening laboratory results (haematology and chemistry that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance No contraindications to having a lumbar puncture examination found on MRI of the brain Exclusion Criteria: current alcohol abuse or drug dependence positive urine drug of abuse screening active opportunistic infection or significant co-morbidities current disallowed concomitant medication (as listed in section 4.1.3) contraindication to MR examination or lumbar puncture examination recent head injury (in last 30 days) or chronic ongoing neurological diseases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rilpivirine and Truvada<br>TDF/FTC (Truvada™) one tablet once plus Rilpivirine 25 mg daily | Drug: Rilpivirine<br>* Rilpivirine 26mg<br>* Other names: Edurant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSF:Plasma Ratio of Rilpivirine Levels | The levels of rilpivirine will be measured in the cerebral spinal fluid and plasma after 60 days of exposure | Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With HIV Viral Load Above 50 Copies Per mL | Plasma viral load will be measured at all study visits to assess if viral load is above the lower limit of detection (50 copies mL) | Day 3,14, 28, 60, 80-100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rilpivirine CSF pharmacokinetics