Clinical trial NCT01562886: The Rilpivirine Cerebrospinal-fluid (CSF) Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Keywords: Rilpivirine CSF pharmacokinetics
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2012-03-26
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: CSF:Plasma Ratio of Rilpivirine Levels
timeFrame: Day 60
Secondary outcomes:
measure: Number of Subjects With HIV Viral Load Above 50 Copies Per mL
timeFrame: Day 3,14, 28, 60, 80-100
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Alan Winston, MBChB MD
role: PRINCIPAL_INVESTIGATOR
References: